FREDS STORY by Dave Whitchurch
Effects on gender identity of prenatal androgens and genital appearance: To address questions about sex assignment in children with ambiguous genitalia, we studied gender identity in girls with congenital adrenal hyperplasia CAH in relation to characteristics of the disease and treatment, particularly genital appearance and surgery.
A 9-item gender identity interview was administered to 43 girls with classical CAH ranging in age from yr, 7 tomboys, and 29 sister control girls. Groups were compared on total score and on individual items. On individual items of gender identity discomfort as a girl, wish to be a boy , girls with CAH were similar to control girls. Gender identity in girls with CAH was not related to degree of genital virilization or age at which genital reconstructive surgery was done.
Thus, moderate androgen excess early in development appears to produce a small increase in the risk of atypical gender identity, but this risk cannot be predicted from genital virilization. Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone GnRH neurons that is reversed by metformin treatment in adulthood.
Prenatal androgenization PNA of female mice with dihydrotestosterone programs reproductive dysfunction in adulthood, characterized by elevated luteinizing hormone levels, irregular estrous cycles, and central abnormalities. Here, we evaluated activity of GnRH neurons from PNA mice and the effects of in vivo treatment with metformin, an activator of AMP-activated protein kinase AMPK that is commonly used to treat the fertility disorder polycystic ovary syndrome.
Estrous cycles were monitored in PNA and control mice before and after metformin administration. Before metformin, cycles were longer in PNA mice and percent time in estrus lower; metformin normalized cycles in PNA mice. Extracellular recordings were used to monitor GnRH neuron firing activity in brain slices from diestrous mice. Compound C stimulated cells from metformin-treated, but not untreated, mice, suggesting that AMPK was activated in GnRH neurons, or afferent neurons, in the former group. GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose.
These studies indicate that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by metformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome. The inducing was performed through surgery to subcutaneously implant sillicon pellets suffed with 1 ml of testosterone propionate which were replaced at every 4 weeks.
Prenatal testosterone T excess increases ovarian follicular recruitment, follicular persistence, insulin resistance, and compensatory hyperinsulinemia.
Considering the importance of insulin in ovarian physiology, in this study, using prenatal T- and dihydrotestosterone DHT, a nonaromatizable androgen -treated female sheep, we tested the hypothesis that prenatal androgen excess alters the intraovarian insulin signaling cascade and metabolic mediators that have an impact on insulin signaling. Importantly, prenatal T excess induced age-specific changes in PPARG and adiponectin expression, with increased PPARG expression evident during fetal life and decreased antral follicular adiponectin expression during adult life.
Comparison of developmental changes in prenatal T and DHT-treated females found that the effects on PPARG were programmed by androgenic actions of T, whereas the effects on adiponectin were likely by its estrogenic action. These results suggest a role for PPARG in the programming of ovarian disruptions by prenatal T excess, including a decrease in antral follicular adiponectin expression and a contributory role for adiponectin in follicular persistence and ovulatory failure.
Non-classic androgen actions in Sertoli cell membrane in whole seminiferous tubules: Studies show a mechanism of action of testosterone, nandrolone and catechin as agonists of the membrane androgen receptor. The aim of this work is to investigate the non-classical effect of androgens and catechin in Sertoli cells from immature rats. The membrane potential of Sertoli cells in whole seminiferous tubules was recorded using a standard single microelectrode technique. Testosterone produces a depolarization in the membrane potential at s after application.
The same response of catechin and nandrolone was observed at different doses. The effects of testosterone, catechin and nandrolone were not affected after perfusion with flutamide. These results indicate that nandrolone and catechin act through a receptor on the plasmatic membrane, as well as testosterone, showing a non-classical pathway in Sertoli cells from immature rat testes.
Androgens and bone health. Osteoporosis is one of the most common metabolic bone diseases in the adult population and its prevalence will continue to rise as our population grows older. In both sexes, hypogonadism is associated with accelerated loss of bone and development of osteoporosis. Adrenal and gonadal androgen levels decline with advancing age in both sexes.
Androgens act by either directly binding to androgen receptors, or by aromatization of androgens to estrogens and subsequently interacting with estrogen receptors. Both pathways are important for skeletal health. Direct androgen binding to an androgen receptor may play a more important role in early skeletal development and determination of sexual dimorphic traits. While bone remodeling, which is important in maintaining healthy bone through life, is primarily stimulated by estrogen, studies in the rat and human support the complex action of androgens and estrogens in bone modeling and remodeling, and hence the development and maintenance of healthy bone.
In postmenopausal females, the addition of androgens to hormone replacement therapy results in significant additional improvement in bone mineral density compared to estrogen replacement alone. Accumulating evidence indicate that androgens play an important role in the health of bone and the potential benefit of adding these agents to hormone replacement regimens.
Although androgens have been considered essential modulators of bone biology in men, recent studies have indicated that estrogen may have an important, if not dominant, role. Nevertheless, there is strong evidence that androgens have independent skeletal actions. Nonaromatizable androgens influence a variety of aspects of bone cell biology and are capable of modulating bone remodeling and bone mass.
It appears that androgens are particularly important in the control of periosteal bone formation, an effect that might underlie the gender difference in bone size. Alterations in androgen receptor function affect bone metabolism, and new information suggests that androgens modulate receptor homeostasis. The clinical implications of androgen effects, and how they interact with those of estrogens, are somewhat unclear. It is likely that overall bone homeostasis and gender differences depend on a combination of androgenic and estrogenic actions.
Androgens may well provide advantages in the prevention and therapy of metabolic bone disorders in both men and women. Metabolic control mechanisms in mammalian systems. The evidence indicates that cyclic AMP may be involved in triggering the known metabolic actions of androgens on secondary sexual tissues of the rat. Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens , while body hair growth is dependent on the action of androgens.
Androgenetic alopecia, referred to as male pattern hair loss MPHL in men and female pattern hair loss FPHL in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens , and males with genetic 5alpha-reductase 5alphaR deficiency, who have low levels of dihydrotestosterone DHT , implicate DHT as a key androgen in the pathogenesis of MPHL in men.
The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL.
Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences.
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Copyright Elsevier Science Ireland Ltd. The review is timely given recent advances regarding mechanisms of androgen action on bone cells and in humans. Osteoporosis in men is an important public health problem. An improved understanding of the role of androgens in the pathophysiology of bone loss will lead to new treatments. Androgen receptors are present in most bone cells. Testosterone acts on bone both directly via the androgen receptor and indirectly, following aromatization, via the oestrogen receptor. During skeletal modelling, ERalpha is critical for longitudinal bone growth.
For periosteal growth and bone expansion, androgen receptor activation has a positive effect, whereas ERalpha activation is inhibitory. During skeletal remodelling, both receptor pathways generate similar and additive effects on bone. Androgen deficiency is a common secondary cause of osteoporosis in men and should be treated with testosterone, particularly in symptomatic men. However, lack of efficacy data for testosterone in osteoporosis means it is less useful as a first-line treatment in men with age-related declines in testosterone and osteoporosis, when other agents such as bisphosphonates and parathyroid hormone are effective.
Randomized, placebo-controlled trials of testosterone therapy in men with age-related declines in testosterone and osteoporosis are needed, and should carefully evaluate potential risks, as well as its efficacy in reducing fractures and other health benefits. Prenatal Influences on Human Sexual Orientation: In non-human vertebrate species, sexual differentiation of the brain is primarily driven by androgens such as testosterone organizing the brains of males in a masculine fashion early in life, while the lower levels of androgen in developing females organize their brains in a feminine fashion.
These principles may be relevant to the development of sexual orientation in humans, because retrospective markers of prenatal androgen exposure, namely digit ratios and otoacoustic emissions, indicate that lesbians, on average, were exposed to greater prenatal androgen than were straight women. Thus, the even greater levels of prenatal androgen exposure experienced by fetal males may explain why the vast majority of them grow up to be attracted to women. However, the same markers indicate no significant differences between gay and straight men in terms of average prenatal androgen exposure, so the variance in orientation in men cannot be accounted for by variance in prenatal androgen exposure, but may be due to variance in response to prenatal androgens.
These data contradict several popular notions about human sexual orientation. Sexual orientation in women is said to be fluid, sometimes implying that only social influences in adulthood are at work, yet the data indicate prenatal influences matter as well. Gay men are widely perceived as under-masculinized, yet the data indicate they are exposed to as much prenatal androgen as straight men.
There is growing sentiment to reject "binary" conceptions of human sexual orientations, to emphasize instead a spectrum of orientations. Yet the data indicate that human sexual orientation is sufficiently polarized that groups of lesbians, on average, show evidence of greater prenatal androgen exposure than groups of straight women, while groups of gay men have, on average, a greater proportion of brothers among their older siblings than do straight men. Non-human primates avoid the detrimental effects of prenatal androgen exposure in mixed-sex litters: Producing single versus multiple births has important life history trade-offs, including the potential benefits and risks of sharing a common in utero environment.
Sex hormones can diffuse through amniotic fluid and fetal membranes, and females with male littermates risk exposure to high levels of fetal testosterone, which are shown to have masculinizing effects and negative fitness consequences in many mammals. Whereas most primates give birth to single offspring, several New World monkey and strepsirrhine species regularly give birth to small litters. We examined whether neonatal testosterone exposure might be detrimental to females in mixed-sex litters by compiling data from long-term breeding records for seven primate species Saguinus oedipus; Varecia variegata, Varecia rubra, Microcebus murinis, Mirza coquereli, Cheirogaleus medius, Galago moholi.
Litter sex ratios did not differ from the expected 1: FF for twins and 1: Measures of reproductive success, including female survivorship, offspring-survivorship, and inter-birth interval, did not differ between females born in mixed-sex versus all-female litters, indicating that litter-producing non-human primates, unlike humans and rodents, show no signs of detrimental effects from androgen exposure in mixed sex litters. Although we found no evidence for CYP19A1 gene duplications-a hypothesized mechanism for coping with androgen exposure-aromatase protein evolution shows patterns of convergence among litter-producing taxa.
That some primates have effectively found a way to circumvent a major cost of multiple births has implications for understanding variation in litter size and life history strategies across mammals. The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action , amplifies GnRH-induced LH but not FSH secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol E2 receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis.
We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH GnRH pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release.
Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action , amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release. Fetal programming of adrenal androgen excess: Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation.
In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate DHEAS , typical of polycystic ovary syndrome PCOS women with adrenal androgen excess. DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the hydroxyprogesterone response and reducing the DHEA to hydroxyprogesterone ratio.
Since min post-ACTH serum values for hydroxyprogesterone correlate negatively with basal serum insulin levels all female monkeys on pioglitazone and placebo treatment combined , while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys.
Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.
We aimed to examine this pathway in hepatocarcinogenesis and to identify drug s specifically blocking this carcinogenic event in the liver. Efficacy of several HCC-targeted drugs in suppressing HBx-induced AR activity was evaluated, and cellular factors mediating suppression were investigated in cultured cells. Tissue specificity of the candidate drug was validated using mouse tissues.
Data were analyzed with Chi-square and Student's t tests. All statistical tests were two-sided. The androgen pathway was shown to be important in early stage hepatocarcinogenesis of HBx transgenic mice. Published by Oxford University Press. For Permissions, please e-mail: Molecular insight into the differential anti- androgenic activity of resveratrol and its natural analogs: In Silico approach to understand biological actions.
The androgen receptor AR is a therapeutic target for the treatment of prostate cancer. Androgen receptor reactivation during the androgen -independent stage of prostate cancer is mediated by numerous mechanisms including expression of AR mutants and splice variants that become non-responsive to con Bolandiol is a synthetic anabolic steroid that increases lean body mass and bone mineral density without significant stimulation of sex accessory glands in castrate adult male rats. Since bolandiol suppresses gonadotropins and endogenous testosterone T production, we investigated its mechanism of action.
In immature castrate rats, bolandiol was equipotent to T in stimulating growth of the levator ani muscle but less potent than T in stimulating growth of the sex accessory glands. Bolandiol also stimulated uterine weight increases in immature female rats, which were partly blocked by ICI ,, but it was not aromatized in vitro by recombinant human aromatase. Osteopenia as a feature of the androgen insensitivity syndrome. The syndrome of androgen insensitivity, a paradigm of a hormone resistance syndrome, manifests as failure of masculinization despite normal or high concentrations of serum testosterone.
The defect in these 46 XY patients resides in the androgen receptor gene, with consequent defective androgen action and abnormal sexual differentiation. We sought to evaluate whether the adverse sequelae of androgen resistance may extend to skeletal tissue by measuring bone mineral density in six patients with androgen insensitivity. A cross-sectional retrospective study. The diagnosis of androgen insensitivity was confirmed in each patient by karyotype and assay of sex hormones.
The five adult patients with androgen insensitivity had been exposed to both defective androgen action and variable periods of oestrogen deficiency. The latter resulted from the low circulating oestrogen concentrations for premenopausal females before gonadectomy and inadequate oestrogen replacement after gonadectomy. All five adults with androgen insensitivity had osteopenia in both the lumbar spine T-score Osteopenia in patients with androgen insensitivity may relate to defective androgen action , oestrogen deficiency or a combination of the two.
These observations have implications for the management of patients with androgen insensitivity and may provide insight into the effects of androgens on the female as well as the male skeleton. Prenatal exposure to testosterone disrupts both the positive feedback action of E2 and sexual behavior although the mechanisms remain unknown. The current study tested the hypothesis that both prenatal and postnatal steroids are required to organize the surge and sex differences in reproductive behavior. Our approach was to characterize the LH surge and mating behavior in prenatally untreated Control and testosterone-treated T female sheep subsequently exposed to one of three postnatal steroid manipulations: All females were then perfused at the time of the expected surge and brains processed for estrogen receptor and Fos immunoreactivity.
No surges were produced when progesterone was administered concomitantly with E2. The percentage of estrogen receptor neurons containing Fos was significantly influenced in a brain region-, developmental stage-, and steroid-specific fashion by testosterone and E2 treatments. These findings support the hypothesis that the feedback controls of the GnRH surge are sensitive to programming by prenatal and postnatal steroids in a precocial species.
Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only.
Production of progestin 20alpha-dihydroprogesterone, as measured by radioimmunoassay remained unimpaired in the presence of androstenedione Ad and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture.
Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production. Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. Androgen regulation of androgen receptor AR expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen.
AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a time- and dose-dependent fashion. Reporter assays with 2. Treatment with other steroid hormones, including progesterone, 17beta-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts.
This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue.
Androgens in health and disease: Moreover, recent results also make it clear that androgens utilize a variety of signaling molecules to exert their effects on the brain, which may or may not depend on the classic nuclear androgen receptor AR. The papers in this issue underscore these two points. This overview is not intended as a comprehensive review of androgen action on the nervous system, since the papers in this issue serve that purpose, but rather to frame the basic issues and themes that tie these papers together. The sum effect of the stories told in this issue encourages us to broaden and refocus our view of androgen action on brain and behavior—to recognize that androgens affect many aspects of brain structure and function throughout the lifespan, from shaping its sexual phenotype to influencing its propensity for disease and repair, and that at least some of these actions are exerted via non-classical modes of action that in many cases were first identified in non-neural tissue or cells.
Prenatal testosterone excess programs an array of adult reproductive disorders including luteinizing hormone excess, functional hyperandrogenism, neuroendocrine defects, polycystic ovarian morphology, and corpus luteum dysfunction, culminating in early reproductive failure. Polycystic ovarian morphology originates from enhanced follicular recruitment and follicular persistence.
We tested to determine whether prenatal testosterone treatment, by its androgenic actions , enhances follicular recruitment, causes early depletion of follicular reserve, and disrupts the ovarian architecture. Pregnant sheep were given twice-weekly injections of testosterone or dihydrotestosterone DHT , a nonaromatizable androgen , from Days 30 to 90 of gestation. Results revealed no differences in numbers of oocytes and follicles between the three groups on Fetal Day Greater numbers of early growing follicles were found in prenatal testosterone- and DHT-treated fetuses on Day Increased numbers of growing follicles and reduced numbers of primordial follicles were found in mo-old, prenatal testosterone-treated females, but not in those treated with DHT.
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Antral follicles of prenatal testosterone-treated females, but not those treated with DHT, manifested several abnormalities, which included the appearance of hemorrhagic and luteinized follicles and abnormal early antrum formation. Both treatment groups showed morphological differences in the rete ovarii. These findings suggest that increased follicular recruitment and morphologic changes in the rete ovarii of prenatal testosterone-treated females are facilitated by androgenic programming, but that postpubertal follicular growth, antral follicular disruptions, and follicular depletion largely.
Androgens activate a protein called the androgen receptor AR , which Although powerful anti- androgen drugs can be administered to block AR action and have been used successfully to. The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor AR through the use of genetically modified mouse models.
These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action , and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.
Androgen antagonists in androgen target tissues. Most antiandrogens appear to act by binding to the androgen receptor and competitively inhibiting the binding of testosterone and cihydrotestosterone to the receptor. Focusing on those compounds which appear to inhibit androgen receptor mediated responses, this review discusses the chemistry of those antiandrogens which have been studied to the extent that their mechanism of action is at least partially understood, outlines the mechanism of androgen action as it is currently understood and suggests how antiandrogens might fit in with this mechanism, indicates the major metabolites of several important antiandrogens, and discusses the clinical applications of several antiandrogens.
Cyproterone acetate has been studied extensively as a potential male contraceptive. Although it was recognized that mg of cyproterone acetate per day inhibited spermatogenesis, that dose also reduced libido and potency. Following the administration of 10 or 20 mg of cyproterone acetate per day to 15 males for 26 weeks, the following observations were made: Sperm density was also suppressed, but neither it nor sperm motility were inhibited to the extent necessary for contraception.
Antiandrogens have been demonstrated to be beneficial in treating 5 clinical syndromes or diseases: Since 3 of these conditions are very common, effective and safe treatment would have a large market. At this time, antiandrogens are widely used in Europe for treatment of seborrhea, acne, and hirsutism and a large Veterans Administration Cooperative Study in the US was approved but has not yet been funded to compare antiandrogens with other treatments for cancer of the prostate.
Androgens are hormones that play a critical role in stimulating prostate cancer growth. Manipulation of pre and postnatal androgen environments and anogenital distance in rats. We examined the anogenital distance AGD plasticity in rats through the manipulation of the androgen environment in utero and during puberty. After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats.
Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure. Understanding the physiology of pregnancy enables effective management of pregnancy complications that could otherwise be life threatening for both mother and fetus.
A functional uterus i retains the fetus in utero during pregnancy without initiating stretch-induced contractions and ii is able to dilate the cervix and contract the myometrium at term to deliver the fetus. The onset of labour is associated with successful cervical remodelling and contraction of myometrium, arising from concomitant activation of uterine immune and endocrine systems. A large body of evidence suggests that actions of local steroid hormones may drive changes occurring in the uterine microenvironment at term. Although there have been a number of studies considering the potential role s played by progesterone and estrogen at the time of parturition, the bio-availability and effects of androgens during pregnancy have received less scrutiny.
The aim of this review is to highlight potential roles of androgens in the biology of pregnancy and parturition. A review of published literature was performed to address i androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, ii associations of androgen concentrations with adverse pregnancy outcomes, iii the role of androgens in the physiology of cervical remodelling and finally iv the role of androgens in the physiology of myometrial function including any impact on contractility.
Some, but not all, androgens increase throughout gestation in maternal circulation. The effects of this increase are not fully understood; however, evidence suggests that increased androgens might regulate key processes during pregnancy and parturition. For example, androgens are believed to be critical for cervical remodelling at term, in particular cervical ripening, via regulation of cervical collagen fibril organization. Additionally, a number of studies highlight potential roles for androgens. METHODS A review of published literature was performed to address i androgen concentrations, including biosynthesis and clearance, in maternal and fetal compartments throughout gestation, ii associations of androgen concentrations with adverse pregnancy outcomes, iii the role of androgens in the physiology of cervical remodelling and finally iv the role of androgens in the physiology of myometrial function including any impact on contractility.
Additionally, a number of studies highlight. Effects of androgens on cardiovascular remodeling. Androgens , the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor AR. ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are well-known to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality.
However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males. Prenatal testosterone T excess leads to reproductive dysfunctions in sheep, which include increased ovarian follicular recruitment and persistence. To test the hypothesis that follicular disruptions in T sheep stem from changes in the developmental ontogeny of ovarian proliferation and apoptotic factors, pregnant Suffolk sheep were injected twice weekly with T propionate or dihydrotestosterone propionate DHT; a nonaromatizable androgen from Days 30 to 90 of gestation.
Prenatal T treatment induced changes in expression of proliferative and apoptotic markers in a follicle-, age-, and steroid-specific manner. Neither treatment affected FAS expression at any developmental time point in any follicular compartment. Lateralization of the brain is strongly influenced by prenatal androgens , with differential exposure thought to account for cognitive sex differences.
This study investigated sex and individual differences and relationships between 2D: Androgen -Induced Cell Migration: Background Androgen receptor AR controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive.
We now report that, through extra nuclear action , AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R We analyzed the initial events leading to androgen -induced cell migration and observed that challenging NIH3T3 cells with 10 nM R rapidly induces interaction of AR with filamin A FlnA at cytoskeleton. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase FAK , paxillin and Rac, thereby driving cell migration.
Interestingly, FAK and Rac activation by androgens are independent of each other. Some sympathisers also helped deserters — men on the run from the army, who numbered in the thousands. There were severe penalties for anyone caught helping people to evade military service — as we will see next month when we tell the tale of a Bedminster shopkeeper who seems to have succeeded for years in hiding draft-dodgers and COs in a secret chamber under his shop.
When tens of thousands of men could be killed in the trenches in a single day, the need for manpower was huge. Government propaganda tried to persuade men that they owed it to their comrades to share the risks of battle. Few chose to resist establish his kingdom by force. I firmly believe that to engage either directly or indirectly in militarism or war is contrary to the teachings of Jesus. Roland, who was 21 when conscription began in , was training as a carpenter. The treatment of COs was often thought of as harsh — and it was.
But Roland Reinge faithfully records the opportunities the. On their first appearance before a tribunal in early , Sidney and Roland were given an exemption from military service. This sounds ideal, but Roland wanted a ruling without conditions, so they appealed. So keen Continued overleaf. He told the tribunal: At an earlier tribunal the brothers were asked: He appealed against his conscription and lost. On August 25, , he disappeared. But Hutchinson was caught and tried before Bristol magistrates on December 12, They attended meetings of the Quakers, where members are allowed to form their own beliefs, as well as Totterdown Methodist church.
But this latter church was part of the war movement as far as Roland was concerned. It struck Roland that. If you know anything about the people featured in this article or any other local COs please email rememberingrealww1 gmail. A police wagon, drawn by a horse, arrived at Oxford Street and took the brothers first to Knowle police station at that time in Calcot Road and then on to the Bridewell before they were brought before the magistrates. The brothers had already been summoned to military service, and had ignored the call, so they were now technically deserters.
If we persisted in our attitude it might result in very serious. Otherstory wants to hear from people who have their own family connections to the anti-war movement. It has already mounted an exhibition which has been seen in Bristol Cathedral, where one woman walked in to see a picture of her grandfather in a group of conscientious objectors held at Dartmoor prison. Many families did not talk about men who refused to fight; but others were proud of their resistance, which took courage and determination. Many were imprisoned without their families even knowing where they were.
The workshops will show people how to research the history of war resistance in South Bristol around World War I. We told him we were sorry we could not alter our views and quite understood the seriousness of our position. He suggested that, at least, we take the money he had offered us. He was very cunning and polite. We replied that it was not our wish to be considered soldiers and we had no desire to accept army money. The brothers spent Christmas in the barracks. The other soldiers were mostly kind to them, even sharing their Christmas presents, and seemed impressed when the Reinges refused to stand for an officer.
They even refused to answer their names to a roll call, but a corporal answered for them. The charade continued when.
George Barker and his cycle shop in the Otherstory puppet show. The workshops will run from January to March in Bedminster. The Otherstory website reveals more. Of course, they refused. This was taken as their first refusal of a military order, and they were put in detention to await a court martial.
Two days before the court martial, they had a visit from an army chaplain. This encounter confirmed the sharp contrast between the behaviour which the brothers believed was required by their understanding of Christianity, and the conduct most clergy expected. He asked us to seriously consider our position and reflect on our duty to the country and our fellow men. He also dwelt on the general disgrace and the serious position we were now in. Here the visit ended and we did not see him again. Hard labour could have been worse: The regime, though, was hard to bear. The first month was spent in solitary confinement with a short period of exercise each day.
During the first two weeks prisoners had to sleep on bare boards; a hard mattress was issued after two weeks. But soon hunger won him over and he wolfed down the pint of porridge issued morning and evening with six ounces g of bread. Lunch was potatoes and bread with the addition of a small lump of rancid bacon on Mondays, a small portion of meat in a stew on Tuesdays and Continued overleaf. Even the court martial was a fairly restrained affair.
The sentence was delivered to the brothers on a parade ground full of hundreds of soldiers. They were sentenced to days hard labour in Wormwood Scrubs jail in London. Any food uneaten was eagerly traded by other prisoners. At the end of the day sentence there was more comedy, when it transpired that a single sergeant was to escort them back to the Wiltshire army camp. The meal with their maiden aunt was a huge delight to the brothers, and as the sergeant seemed to enjoy himself too, they chanced their arm and asked if they could also drop in on Uncle Tom and Aunt Harriet, who lived nearby.
This too was agreeable to the sergeant, who was probably having more fun than he had at the army camp, and the trio did not arrive back in Wiltshire until after midnight. Then the charade started again: This time the sentence was one year, served in Winchester prison. It was the same dreary routine as before, with the prisoners trying to lever every little bit of autonomy they could. On most occasions they were not even allowed to speak to each other, so opportunities for rebellion were limited.
On one occasion a sermon about the war at the Sunday service provoked the prisoners to stamp their feet in unison. Another time, a serving of suet pudding, considered one of the better items on the menu, was replaced by a plate of hard, red herrings. Granted subject to conditions. Construction of 4-bedroom dwelling next to 18 Victoria Place.
A rare photo of conscientious objectors at the Home Office work camp at Dartmoor prison in By kind permission of Paul Shotton. One day Roland was seen talking to a fellow prisoner and sent to a basement cell for three days on bread and water. But they were comforted by the kindness of a prison warder who, against rules that forbade him from a private conversation with a prisoner, visited Roland in secret one evening. He inquired after his health, passed on a message from Sidney, and promised to take a message back.
This time it was Shepton Mallet jail, where Roland had an enviable view from his top-floor cell of a cottage, which comforted him — even though looking out of his window was against the rules, and he could be punished for it. The situation of the jail, high on the fog-shrouded moor, was forbidding, but the brothers were relieved that the work — in the laundry or on the prison farm — was not contributing to the war effort, and they could do it with a clear conscience.
They were no longer technically prisoners, and they had unexpected freedoms. They were allowed to move around the prison in the evenings and talk to the hundreds of other COs there. Most were determined to do nothing that supported war in any way, but some socialists were prepared to fight if the object was to overthrow capitalism. He clearly regarded his time as a CO as the most important period of his life. The Reinge brothers went on to run a successful housebuilding business in South Bristol.
The city record office contains their plans for seven houses in Crowndale Road,. He lived in Crowndale Road, perhaps in one of the houses his brothers built. He died in Sidney died in Sadly, Roland had died in , before Shirley had finished typing his memoir. Includes list of all known COs. The incredible tale of the Bedminster cycle shop owner who hid conscientious objectors underground. The Old Tabernacle, Palmyra Road BS3 3JQ Roof extensions and external alterations to provide five 1-bedroom flats, parking for five cars, cycle, bin and recycling storage.
Granted subject to conditions 9 Gore Road BS3 2LX Demolition of house and erection of 3-bedroom two storey dwelling with roof extension. Patio doors in rear wall. Check for updates at planningonline. Scary stories, creepy creations and hair-raising hijinks. All-day sessions for year olds on October 29 and for years on October Work with Laura from Colourful Minds to make spooky stained glass window decorations and nightlights. Plus extra activities for little ones. More Halloween and half term activities on the website.
Leave your computer behind and experience gaming themes outdoors around the farm. For 6 to 9 year olds. Catch 22 productions present awardwinning Spanish garage rockers Agoraphobia on their first UK visit, while Bristol-based headliners White Lion Parade strive to create easy listening for metal fans. The new Spielman theatre is the setting for this new play looking at gender stereotypes in a fun, questioning way, for over-7s.
A group of mums have stormed the comfy sofas, and another cluster sit cross-legged on the floor with their little ones in a play area. Weekly performances in a variety of genres. Free entry, collection, 1. There are babies who look only a matter of weeks old, up to 18 months — the age limit for small people. It just happens to be on during the day, with babies in tow.
There are babies sleeping, feeding, crawling about, looking dumbstruck or intrigued. There is surprisingly little crying — my theory is that the mums mostly and smattering of dads in attendance are relaxed, and this rubs off on their offspring. You have to respect the comedians — Swindonian Ed Pownall had some great takes on the air quality in their park or neighbourhood, then brainstorm ideas to improve their air and make posters. Free, but register first.
Jenny Williams, an ex-police detective, is training up another team of year olds in crime scene investigation. More than 40 artists showcasing and selling original, handcrafted work in painting, printing, textiles, ceramics, felt, glass, pastel, silver, wood, batik and more. Free taster art workshops and demonstrations. The famous weekly market with around 40 craft and food stalls, focused on local, ethical and fairly traded products.
The infamous Zion quiz will stretch your brains. Nick Makoha presents a poetry masterclass on Saturday at 11am. Cohen Braithwaite-Kilcoyne is an award-winning young singer who plays melodeon and anglo concertina. Sadly this is the nextto-last show for the Saltcellar, which closes in December due to a lack of volunteers. So, the old TF was welcoming in its spanking new Spielman Theatre with a touch of glitz? This hour-long show by. Killer lines and a great curry n Review Alfie Moore: Anyone who has spent any off-duty time with police officers will know that, like doctors, they often have a bleak sense of humour.
Let loose with a live audience, though, and Alfie is more of a comedian, luring the audience into his traps. Monday November 12 n Aftermirth! The return of the comedy club for parents and offspring who are too young to understand the swearing that is, under 18 months. Toys, food, and live comedy, headlined by Sally-Anne Hayward, festival veteran and fresh from supporting Sarah Millican.
Underneath the fixed grins and staged poses was an aching need to convey that they were capable of far more than this. Impressive displays of body-twisting trickery were accompanied by a constant talkback, informing us of the limitations forced on women. Each display of cartwheels and backflips ended with a defiant stare at the. The evening is billed as a how-to guide to permanently dispose of an unwanted relative.
Alfie swiftly picks on an unfortunate husband in the audience, and identifies, with the. You could dwell on the ideal way to dispose of body parts for too long. Alfie suggested to the nominally murderous wife that she could contract out the killing. Hats off to Entertaining Local Knowle, who persuaded Alfie Moore to play this small venue, which works very well for comedy. The inclusion of a fine curry from Knowle chef Sebastien Brochot made it a great evening.
In the depths of the Underworld, Hades is in charge — but can he keep control of his naughty demons and unruly souls? A quirky, fun take on. Greek mythology, with a bit of Bristol mixed in. Not suitable for very young children. Over 18s only, bar. Inadvertently, I framed the wrong suspect. We can aim higher audience, which spoke volumes. As did the constant shutting down of Alice Gilmartin, who throughout the show tried to make a speech but each time was told to do a handstand and smile, as that was all the audience wanted of her.
As Michelle Ross spun fantastically on the Cyr wheel, a heavy, human-sized ring of iron, we were talked through the myriad. McWilliam tried, unsuccessfully, to break the world record for cartwheels in a minute. She reached 56, and was left breathless. Francesca Hyde hung and twirled from her hair, bouncing playfully, then Bing crooned again as the five oh-so talented acrobats sat in a line, staring at the audience and eating doughnuts.
This was a show that was a no-show after all — because for it to be a show they would have to be allowed to perform to the full with no constraints. A bold and thought-provoking start for an exciting new space. Organ, piano, singers and audience participation. Collection in aid of Brace, the Alzheimers research charity. An exhibition about bringing art out of city centre galleries and into the community. Paul Trevor talks about his arresting close-up street portraits, shot in London between and Exhibition runs until December Yes, you did see her on Later with Jools Holland in October!
From Mali, Diawara now lives in France, and is known for her haunting voice and expert guitar work. In our digital world, can a hand-written letter change a life? For someone feeling isolated through illness, a letter or card could be the connection they need. A free workshop where you can put pen to paper for a friend,. Cartoon vividly brought to life n Review: Our heroes Alex the lion and Marty the zebra live in New York zoo, until an escape plot by the penguins ends with them washing up on the Indian Ocean shores of Madagascar.
From start to finish our children were mesmerised by. Festive attractions from 12 noon Catch him quick before the venues get bigger: Rhys James, known as the funniest man on Twitter, is making his mark on Mock the Week. With Alistair Williams and compere Clint Edwards. Dave Merrick and Clive Mills use live music, multi-media and spoken word to bring to life the original US protest singer, who influenced Bruce Springsteen, Bob Dylan, and many others.
If it were 15 degrees warmer you would have believed you were actually in Madagascar! Brandon Gale did the king of the jungle justice, with stage presence, rhythm, a great voice and some funny lines. Gloria the Hippo, played by Timmika Ramsay, used her singing talent to belt out some catchy numbers which had the audience tapping their feet in delight. King Julien the ring-tailed lemur was brilliantly played by Jo Parsons.
His number I Like to Move It had some of the young audience dancing in their seats. But the star of the show for us North Street, Southville. Call Anne on King of the stage: Alex the lion was the cranky, hypochondriac giraffe Melman, played by Jamie Lee-Morgan. However, this mum thought it was a great night out. Thursday November 22, 10am-1pm, registration and coffee from 9. The venue is wheelchair accessible. For information on the venue: The events are free and lunch is provided.
For details, email Ruth. Thursday November 15, 10am-1pm, registration and. The Monday Club for older people at the Southville Centre is looking for volunteers. This social club takes place every week at the Southville Centre. Could you tell a neighbour or a friend or family member that might be interested in a volunteering opportunity?
Might you be available on Mondays 10am-4pm? We can provide free transport and a free lunch to volunteers. Do you have the odd hour or two to spare? Can you drop in to help us serve lunches, or escort people on the mini-bus, or do you have an area of expertise you could share by giving a talk, helping with arts and crafts, giving a musical performance? Contact Tricia Mason, qualified teacher, The Scrumpy I am talking about is the amiable mascot who wanders around posing for photos with anyone with a child or not fast enough to run away.
Scrumpy, who I believe is loosley based on a robin, first waddled on to the scene in He replaced the previous cat mascot, who had blotted his copybook by getting into a fight with three little pigs and Wolfie. Great to know he is still passing on real knowledge to the younger generation. Anyway, those geniuses at Bristol Aardman Animations came up with Scrumpy and for some reason he had a nose that resembled a traffic cone.
In the last game before the international break, defender Nathan Baker had his own DIY nose realignment on the pitch and spent the last 10 minutes against Sheffield Wednesday looking dazed and confused. With goalkeeper Niki Maenpaa also hobbling, hopes of getting anything from a game that had started brightly fizzled out.
A defeat was chalked up along with a winless run of five. The team started brightly, and had enough. Sheffield Wednesday boasted 36 first team squad players on the matchday programme, while City had Of those, seven were out with injuries. In truth it is a skeleton squad with little cover for some positions, such as those occupied by midfield warhorses Pack and Brownhill.
Questions have to be asked about.
Fred Stansfield
You only have to look at how well Lloyd Kelly has adapted this season to see that young players can improve rapidly if thrown in with the first team. A few wins in November could catapult the club to the upper echelons of the league and the doorstep of the Premiership, but, without strengthening in January, top-flight football seems unlikely to come to BS3 in The Championship break was a time to reflect on the season so far. Perhaps then, Scrumpy will have a little more reason to be leading the cheers.
Bristol South has the highest number of registered carers in the city: Social care or lack of impacts so many. Not investing in the social care infrastructure to support an ageing society in a bid to save money is a false economy. NHS beds are often taken up with people who, had they been able to access sufficient social care in the community, would not have needed hospital treatment.
Those doing the unpaid caring may have to stop working and often find their health starts to suffer, leading to even more demand on our NHS. Personal Training Want a plan that actually works? Immortalise your furry friend with one of my drawings or colourful Rachel Heaton paintings www.
A report from the parliamentary committees on housing, communities and local government, and health and social care, released this summer warned: The report suggests that a social care premium could be added to National Insurance to help fund this. Research suggests that people would be willing to pay this to know that their social care needs would be met later in life. CJ Hole Southville invite you to accept our offer of a free sales or lettings valuation. To arrange an appointment, please telephone the office or call in personally.
One big question Mr Bowles has to answer is whether he will pick up his powers to franchise the buses — meaning he could Independent Community News Network member Twitter: Celia Phipps Labour, Bedminster By phone: To advertise, contact sales southbristolvoice. A regular clean-up after three weeks came up with rubbish, but no needles from drug users. As usual nine local schools are taking part, from local traders and artists. This year Bedminster theatre company Show of Strength will be presenting a brand new street some with up to children.
Bedminster Winter Lanterns Visitors: Pages Space for the home workers A NEW workspace has opened for people who want to rent a desk, as the number of selfemployed people across BS3 continues to grow. Could Brexit affect taking my pet abroad? The final arrangements depend on Brexit negotiations, which are still to be confirmed, but your veterinary surgery will be able to advise you further.
Grant and Fontaine Boy jailed over sex offences A BOY of 13 from Knowle has been sent to a youth detention centre for 16 months after admitting touching women sexually on five occasions. Facilities company Almeda of Keynsham held a fundraising event at Bath racecourse, while the containers to sit on. Artwork made for HBH Daunting: All branches Larger libraries such as Knowle and Bedminster will expect to retain staff. It usually shows between 30 and 50 years old.
Planning is already under way for the event on February 22, 23 and 24, and organisers are hoping to find someone willing to draw up a map of the area. Talk Money - Preparing for Retirement A workshop on planning for retirement, led by financial experts. No fewer than 11 diseases are linked to air quality, including lung development in children.
This was the starting point for the story, which centres on Jack Kelly, a successful BBC arts presenter who is about to end a long career on British TV and move to the US, when his relationship with a fan from the s is suddenly exposed on social media. Mo has only recently moved to Bristol after retiring from Secrets from the past: Spiders are incredibly industrious creatures, serving nature and us with useful ecosystem jobs, being the meaty menu of many food webs, also offering natural pest control, and in between inspiring many a construction engineer, scientist St Forget the fear — spiders are our friends, and Bristol has some real beauties and artist.
But the greenfanged tube web spider is found in Bristol indoors. S waying softly in the shrubs, a few silvery silks flicker in the lustre of autumn light as I approach an ordinary-looking Victorian house in Knowle. I half expected to see the iconic Spider-Man character, but he is missing. Ms Smyth has been trying to tighten rules on young people possessing air weapons after a tragic incident in Hartcliffe in which month-old Harry Studley of Hartcliffe was left with lasting injuries after being shot by a former family friend.
Either drivers in Bristol need to be educated in how to drive properly or the roundabout needs to be redesigned with a Give Way or a Stop sign. Name supplied Please tell us something new AS MUCH as I appreciate South Bristol Voice giving the Mr Rees column inches every month, I would be grateful if his content contained at least some information, preferably about something he has achieved for the city.
On November 12, members Sue and Richard will be showing their The event for November 26 is to be confirmed. The center is a model community of students, administrators, faculty, staff, and service volunteers—from varying religious, ethnic, and cultural backgrounds—who live and work together in harmony. In many ways the center establishes an idyllic pattern of what can happen in this sacred land.
It is not perfect by any means, but it is moving in the right direction. Brothers and sisters, I hope for the day when those who reside in the Holy Land will do so in harmony with one another. It remains unclear to me just how or when the needed events will unfold to bring about this holy status. There is a story in the Bible that I have reflected on many times.
As you may recall, Jacob fled from his brother, Esau, under very unfavorable circumstances. The tension between these two brothers was palpable: And Jacob lifted up his eyes, and looked, and, behold, Esau came, and with him four hundred men. And he divided the children unto Leah, and unto Rachel, and unto the two handmaids. And he put the handmaids and their children foremost, and Leah and her children after, and Rachel and Joseph hindermost.
And he passed over before them, and bowed himself to the ground seven times, until he came near to his brother. This reconciliation required a softening of the heart from both Esau and Jacob. We should not be confused about it and its definition. We hope for certain things, knowing the odds are not in our favor.
When events transpire contrary to our hope, we nonchalantly take little notice of what it was we had hoped. Good luck on that one! In a religious context, however, hope is defined differently. It is a confident expectation of and longing for the promised blessings of righteousness. It demands from us total trust and confidence. Much like faith, hope is unwavering and active. The outcome is certain. Those who have been there know it well. And so we must. We must hope for and pray for peace. We need to discover the supreme truth that indeed our Father is no respecter of persons.
At the present time we are engaged in a project of beautifying the Mount of Olives in Jerusalem by a garden, in memory of Orson Hyde, an early apostle of the Church, and the dedicatory prayer he offered on that site. It is not because we favor one people over another. Jerusalem is sacred to the Jews, but it is also sacred to the Arabs. Both the Jews and the Arabs are children of our Father. They are both children of promise, and as a church we do not take sides. The purpose of the gospel of Jesus Christ is to bring about love, unity, and brotherhood of the highest order.
Again, the details of how peace will come about may elude us, but I believe—and have hope—that it will happen. Last week in a phone conversation with Eran Hayet, I told him about speaking today and asked if he had anything he wanted to share with you. He said to tell you that years ago Orson Hyde came to Jerusalem to pray over the land and that we need to continue those prayers today. Whitchurch, a BYU associate professor of ancient scripture, delivered this devotional address on October 4, Pratt, , 7. Deseret News, , American Publishing Company, , While the cruise visited various places throughout Europe and Egypt, the main feature of the cruise was to visit the Holy Land.
Hyde provided limited details about much of his journey to and from Jerusalem. It appears, however, that he used waterways throughout his travels. This type of travel added significantly to the total miles because of meandering rivers and indirect routes. Traveling via the Rhine and Main Rivers adds miles to the trip. Total travel distance from Nauvoo to Jerusalem and back to Nauvoo is estimated to be 18, miles. In his letter he reported progress of his travels and included a copy of a letter he wrote to Solomon Hirschell, the chief rabbi of England — Hyde wrote the following in his letter: Smith, and Richard Lloyd Anderson, eds.
The details of how these promises will be fulfilled remain unclear. Due to the death of his mother when he was seven years old, Orson Hyde was placed under the care of a farmer named Nathan Wheeler. Nathan drowned when Orson was twelve years old. Three days after his baptism, Hyde reported: The story of Joseph Smith asking for money is included in a letter written by Mrs. Hill, dated May 19, Joseph Ellison Beck joined the Church in He and his family migrated to Utah in Elder Page wrote Joseph Smith from Philadelphia six months later to explain why he had not left for Jerusalem.
Elder Smith offered to assist Page in every way possible to help him succeed. This letter by Orson Hyde is important in three ways: Hyde wrote two letters while in quarantine: In portions of these letters he briefly recounted the difficulties of the trip and the state of lawlessness he found in Lebanon and Egypt. Orson Hyde, letter to Parley P. See Hyde, letter to Parley P. Bookcraft, , Continuing Education, BYU, , BYU Press, —76 , 3: Smith, project financial manager; and Fred A.
Twenty-nine subcontractors would also be involved with more than three hundred suppliers who provided materials. From a personal correspondence between the author and R. Kirk Belnap, who was present at the Jerusalem Center dedication. Picador, , Credit and thanks go to Russell C. Taylor for pointing this out following the devotional presentation on October 4, See 2 Nephi See the complete list of abbreviations HERE.
Your browser does not support the audio element. Elder Snow described his experience this way: Today I would like to respond to that question by sharing with you three miraculous events connected to the Restoration of the gospel of Jesus Christ that occurred in the Holy Land: The revelation that followed stated: