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PubMed2005

Immunohistochemical evidence for an endocrine/paracrine role for ghrelin in the reproductive tissues of sheep.

BACKGROUND: The gut hormone, ghrelin, is involved in the neuroendocrine and metabolic responses to hunger. In monogastric species, circulating ghrelin levels show clear meal-related and body weight-related changes. The pattern of secretion and its role in ruminant species is less clear. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation. There is also evidence that ghrelin is involved in reproductive function. In the present study we used immunohistochemistry to investigate the presence of ghrelin and GHSR-1a in sheep reproductive tissues. In addition, we examined whether ghrelin and GHSR-1a protein expression is developmentally regulated in the adult and fetal ovine testis, and whether there is an association with markers of cellular proliferation, i.e. stem cell factor (SCF) and proliferating cell nuclear antigen (PCNA). METHODS: Antibodies raised against ghrelin and its functional receptor, GHSR-type 1a, were used in standard immunohistochemical protocols on various reproductive tissues collected from adult and fetal sheep. GHSR-1a mRNA presence was also confirmed by in situ hybridisation. SCF and PCNA immunoexpression was investigated in fetal testicular samples. Adult and fetal testicular immunostaining for ghrelin, GHSR-1a, SCF and PCNA was analysed using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference. RESULTS: In adult sheep tissue, ghrelin and GHSR-1a immunostaining was detected in the stomach (abomasum), anterior pituitary gland, testis, ovary, and hypothalamic and hindbrain regions of the brain. In the adult testis, there was a significant effect of season (photoperiod) on the level of immunostaining for ghrelin (p < 0.01) and GHSR-1a (p < 0.05). In the fetal sheep testis, there was a significant effect of gestational age on the level of immunostaining for ghrelin (p < 0.001), GHSR-1a (p < 0.05), SCF (p < 0.05) and PCNA (p < 0.01). CONCLUSION: Evidence is presented for the presence of ghrelin and its receptor in various reproductive tissues of the adult and fetal sheep. In addition, the data indicate that testicular expression of ghrelin and its receptor is physiologically regulated in the adult and developmentally regulated in the fetus. Therefore, the ghrelin ligand/receptor system may have a role (endocrine and/or paracrine) in the development (cellular proliferation) and function of the reproductive axis of the sheep.

Abomasum↗
PubMed1986

The proenkephalin gene is widely expressed within the male and female reproductive systems of the rat and hamster.

The distribution of proenkephalin mRNA in reproductive tissues of the rat and hamster was examined by Northern analysis and RNA blot hybridization. In the male reproductive tract of both species, proenkephalin mRNA was detected in the testis, vas deferens, epididymis, seminal vesicles, and prostate. Except in the case of the rat testis, the size of this transcript in each organ was identical to that generally observed in tissues expressing proenkephalin (1450 nucleotides). The major proenkephalin mRNA species expressed in the rat testis migrates as a 1900-nucleotide RNA on denaturing agarose gels. In the male rat and hamster, the highest abundance of proenkephalin mRNA was found in the testis and epididymis. A 1450-nucleotide proenkephalin mRNA also was detected in each of the 3 female reproductive tissues of the rat and hamster that were examined: uterus, oviduct, and ovary. These unusual observations suggest that proenkephalin-derived peptides are synthesized at multiple sites within the male and female reproductive tracts of the rodent and may locally regulate reproductive function.

Animals↗
PubMed1990

Cellular localization of the growth hormone receptor/binding protein in the male and female reproductive systems.

We have used immunohistochemistry to localize GH receptor/binding protein (BP) in the male and female reproductive systems of adult rats. Testes and ovaries from neonatal animals were also examined to determine if GH receptor/BP expression in these tissues is developmentally regulated. Two monoclonal antibodies (MAb 43 and 263) were immunoreactive in identical locations whereas no immunoreactivity was evident when control monoclonal antibodies 7 and 50.8 were used. Localization of the receptor/BP was observed in both the nucleus and cytoplasm of immunopositive cells confirming our recent report of a nuclear GH receptor. Intense GH receptor/BP immunoreactivity in the male reproductive system was evident in the epithelium of the vas deferens and coagulating gland, the prostatic epithelium during the secretory phase, and the ductular epithelium of the coagulating and bulbourethral glands, respectively. Strong immunoreactivity was detectable in the Leydig and Sertoli cells, the epithelium of the ductus epididymis and seminal vesicles and smooth muscle of the tunica muscularis of the vas deferens, septae of the seminal vesicles, and in prostatic fibromuscular stroma. Cells of the seminiferous tubules (spermatogonia, primary and secondary spermatocytes, and spermatids) were moderately immunoreactive. No immunoreactivity was detectable in spermatozoa in the ductus epididymis or vas deferens, in scattered epithelial cells of the ductus epididymis, the prostatic epithelium in the nonsecretory phase, and mucous secreting cells of the bulbourethral glands. Leydig cells of 10-day postnatal rat testis were intensely immunoreactive whereas seminiferous tubular cells displayed homogenous immunoreactivity from moderate to strong. Intense GH receptor/BP immunoreactivity in the female reproductive system was evident in the germinal epithelium, the vascular endothelium of the myometrium, the epithelial lining of the fimbriae and oviduct, the endometrial epithelium and scattered endometrial glands, the mesothelium of the perimetrium, and the vascular endothelium of the endometrium. Strong immunoreactivity was exhibited by scattered oocytes, lutein cells of the corpus luteum, scattered endometrial glands, and the vascular endothelium of the endometrium. Moderate immunoreactivity was evident in scattered oocytes, granulosa cells, theca interna and externa, smooth muscle of the oviduct and myometrium, scattered endometrial glands, and luminally placed endometrial stroma cells. Ovarian granulosa cells from 10-day postnatal rats displayed strong immunoreactivity in contrast to moderate immunoreactivity in adult granulosa cells. In conclusion, we report a widespread distribution of the GH receptor/BP in the reproductive system of the rat by which GH may exert a direct action on reproductive function. The distribution is concordant with a role for GH in epithelial function and/or maintenance and also with a possible role for GH in the integrity of the endometrial vasculature.

Animals↗
PubMed1991

Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels.

The role of thyroid hormones in the testis is unclear, although recent evidence indicates they may be important for testicular development. Here we describe a novel method for increasing adult testicular size in the rat by induction of transient hypothyroidism during neonatal life. Rats were treated with a reversible goitrogen, 6-propyl-2-thiouracil from birth to day 25 when treatment was stopped, allowing return to a euthyroid state. At days 90, 135, 160, and 180, wt and DNA content of the testis, epididymis, ventral prostate, seminal vesicle, and those of some nonreproductive organs were determined, as well as serum levels of testosterone (T) and thyroid hormones. Despite decreased body wts in 90-day and older 6-propyl-2-thiouracil-treated rats, testis wt was increased by 40% and 60% at 90 and 135 days, respectively; maximal increase (80%) occurred at 160 days. These wt increases were accompanied by proportional changes in DNA content. Significant enlargements were also seen in other reproductive organs, but they occurred after a time lag and were smaller in magnitude. Interestingly, serum T levels showed no increase at any age. Weight and DNA content of nonreproductive organs, like body wts, were less than controls at all ages but thyroid hormone levels were normal. Thus, transient hypothyroidism in neonatal rats is associated with lasting enlargements in the ultimate size of testis and other reproductive organs in the adult. These changes are not related to excess T levels. The results indicate early critical influences of thyroid hormones on growth and development of the reproductive system and suggest an experimental model for inducing lasting enlargements in testis and reproductive organs. The model may also be useful for studying regulation of reproductive growth and final size.

Animals↗
PubMed1991

Evidence for an organ- and sex-specific role of basic fibroblast growth factor in the development of the fetal mammalian reproductive tract.

Basic fibroblast growth factor (bFGF) has been implicated as an embryonic mesoderm-inducing factor. It has also been detected in the mesodermally derived fetal and adult reproductive tracts. To address its possible role in the development of the reproductive tract, male and female fetal genital ridges and urogenital (UG) sinuses were transplanted bilaterally under the kidney capsule of syngeneic host rats; the transplants and the hosts were the same sex. Antiserum to bFGF (anti-bFGF) or normal rabbit serum (NRS) was infused into the right renal artery. The transplants on the left uninfused kidney served as internal controls. Upon vascularization, the transplants grow and differentiate essentially normally, but their overall growth after 14 days was reduced by about 40% compared to their growth in situ. Neutralization of endogenous bFGF with anti-bFGF resulted in approximately 41% inhibition of growth in the male genital ridge, but had no effect on the male UG sinus or any component of the female reproductive tract. The growth suppression of the male genital ridge was accompanied by an inhibition of the differentiation of the epididymis. After 7 days of treatment, development of the epididymis was impaired by 75%, and by 14 days, the organ was absent. Previous studies of fetal reproductive tract development have focused on the role of steroids and Mullerian inhibiting hormone. Our studies suggest that bFGF plays a role in the development of the male reproductive tract, especially the epididymis, and further suggest the possible role of this peptide growth factor in a steroid hormone-dependent process.

Animals↗
PubMed1993

Expression of type II activin receptor genes in the male and female reproductive tissues of the rat.

In addition to the feedback regulation of pituitary FSH secretion, gonadal activins have been shown to modulate physiological functions in the reproductive tissues. These observations suggested that activins and the receptors for these peptides may be coexpressed in gonadal tissues. In this study, we have cloned cDNAs encoding two species of type II activin receptors (ActRII and ActRIIB) from rat testicular mRNA and have shown that the two rat activin receptors share 97% similarity in the nucleotide sequence with those reported in the mouse. Two species [6 and 3 kilobases (kb)] ActRII mRNA were identified in all reproductive tissues of adult male and female rats. The 6-kb ActRII mRNA was the abundant form in most of the reproductive tissues. In placenta, the 6- and 3-kb mRNA were present in equal intensity. Interestingly, the ratio of the expression of two species of ActRII mRNA in rat testis changed with age. The 6-kb mRNA was the predominant form in immature 15- and 20-day-old testis, while the 3-kb mRNA increased with age and became the major form in mature testis. In female rats, however, the 6-kb ActRII mRNA was the abundant species in all of the ovaries examined, including immature, normal cycling, and pregnant rats. One major 2.25-kb species of ActRIIB mRNA was identified in all of the reproductive organs examined. Nucleotide sequence analysis of the isolated ActRIIB cDNA clones revealed that ActRIIB2 was the major isoform found in rat testis. The levels of expression of ActRIIB gene in rat testis or ovary were not changed during development. We conclude that 1) both type II and IIB activin receptor genes are widely expressed in the male and female reproductive tissues; and 2) the expression of 6- and 3-kb ActRII mRNA is tissue dependent as well as age dependent in rat testis.

Activin Receptors↗
PubMed1985

Experimental analysis of the reproduction of spindle poles.

We have investigated the functional properties of the mechanisms that control the reproduction of spindle poles in fertilized sea-urchin eggs. By prolonging mitosis by three independent means, we show that a spindle pole can split during mitosis into two functional poles of normal appearance. However, these poles have only half the normal reproductive capacity; each daughter cell that receives a split pole, always forms a monopolar spindle at the next division. Each monopolar spindle appears to be exactly half of a spindle because two of them can come together to form a functional bipolar spindle of normal appearance. The poles of such spindles show normal reproduction in subsequent divisions. By following the development of individual cells with monopolar spindles, we show that such a cell can stay in mitosis longer than normal, and the single pole splits into two asters, which move apart to give a functional bipolar spindle. The poles of such a spindle have only half the normal reproductive capacity, because the two daughters of the cell always form monopolar spindles at the next mitosis. This novel cycle of development is often repeated. The occurrence of such phenomena does not depend upon the method used to induce monopolar spindles. These results show that each normal pole has two polar determinants. The results also demonstrate that the reproduction of spindle poles consists of three distinct events: splitting of the polar determinants, physical separation of the two determinants, and duplication of the determinants to return the pole to a duplex state. Splitting and duplication are distinct events because they can be experimentally put out of phase with each other for several cell cycles.

Animals↗
PubMed2000

Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men.

Blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin (EP), blood cadmium (BCd), serum zinc (SZn), seminal fluid zinc (SfZn), serum copper (SCu), and parameters of semen quality and of reproductive endocrine function were measured in 149 healthy male industrial workers 20-43 years of age. The group contained 98 subjects with slight to moderate occupational exposure to Pb and 51 reference subjects. All of the subjects lived in Zagreb, Croatia. Significant (p < 0.05) correlations of BPb, ALAD, and/or EP with reproductive parameters indicated a Pb-related decrease in sperm density, in counts of total, motile, and viable sperm, in the percentage and count of progressively motile sperm, in parameters of prostate secretory function (SfZn, acid phosphatase, and citric acid in seminal fluid), and an increase in abnormal sperm head morphology, serum testosterone, and estradiol. These associations were confirmed by results of multiple regression, which also showed significant (p < 0. 05) influence of BCd, SZn, SCu, smoking habits, alcohol consumption, or age on certain reproductive parameters. These effects were mainly of lower rank and intensity as compared to Pb-related reproductive effects, whereas BCd contributed to a decrease in sperm motility and an increase in abnormal sperm morphology and serum testosterone. No significant Pb- or Cd-related influence was found on levels of the lactate dehydrogenase isoenzyme LDH-C(4) and fructose in seminal fluid or on follicle-stimulating hormone, luteinizing hormone, and prolactin in serum. The seminal fluid concentrations of Pb (SfPb) and Cd (SfCd) were measured in 118 of the 149 subjects, and a highly significant (p < 0.0001) correlation was found between BPb and SfPb levels (r = 0.571) and between BCd and SfCd levels (r = 0.490). The overall study results indicate that even moderate exposures to Pb (BPb < 400 microg/L) and Cd (BCd < 10 microg/L) can significantly reduce human semen quality without conclusive evidence of impairment of male reproductive endocrine function.

Adult↗
PubMed1996

Male reproductive health and environmental xenoestrogens.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Animals↗
PubMed2004

Behavior change evaluation of a culturally consistent reproductive health program for young Kenyans.

CONTEXT: Few rigorous evaluations have been conducted of locally designed, culturally consistent adolescent reproductive health programs. METHODS: A quasi-experimental research design was used to measure behavioral changes associated with a culturally consistent reproductive health program for young people in Kenya. Baseline and endline surveys were conducted in 1997 and 2001, respectively, in the project and control areas. Multivariate analysis was used to assess whether the project was associated with changes in young people's sexual initiation, safer-sex behavior and discussion of reproductive health issues with adults. RESULTS: The 36-month project was associated with considerable changes in young people's sexual and reproductive health-related behavior, but behavior change differed by gender. Females in the project site were significantly more likely than those in the control site to adopt secondary abstinence (odds ratio, 3.3) and less likely to have had three or more sex partners (0.1). Males in the project site were more likely to use condoms than those in the control site (3.7). Both males and females in the project site were more likely to discuss sexual and reproductive health issues with a nonparent adult than were young people in the control site (1.9 and 5.5, respectively). CONCLUSIONS: Interventions that adapt to indigenous traditions can be both acceptable to communities and associated with significant changes in young people's behavior.

Adolescent↗
PubMedDate not supplied

Leptin, nutrition and reproduction: new insights.

Recent data suggest that in addition to leptin's role in conveying signals of the amount of energy stores to the central nervous system, this adipocyte secreted hormone interacts with the endocrine system to provide critical information about the size of fat stores, acting as a permissive factor that allows the triggering of energy demanding situations as the onset of puberty and reproduction. Animal and human data are concordant with the concept that leptin plays an important permissive role in the initiation of puberty and in maintenance of reproductive function thereafter. Leptin regulates the gonadotropin-gonadal axis at a central level. The hypothalamus is an important site of leptin's action where a complex network of neuropeptides is involved in leptin's effect on GnRH. In addition, leptin plays a role during pregnancy and lactation as it is produced by the placenta and is present in milk. Plasma leptin levels are elevated during pregnancy and this hyperleptinemia is not accompanied by a reduction in food intake, suggesting a state of leptin resistance. Leptin is also detected in the amniotic fluid and its levels are high in venous cord blood at delivery correlating positively with weight at birth which suggests a potential role in intrauterine growth. The fact that in females leptin levels are higher than in males, even when corrected for body fat, suggests that the reproductive system is modulated by leptin in a different way in males and females estrogens. In hypoleptinemia resulting from specific genetic causes, leptin levels may still be adequate for the function of the reproductive system in humans, a phenomenon which differs from the findings in leptin-deficient animals which are infertile. Due to species differences in the role of leptin, it is difficult to extrapolate data from rodents to human physiology. However hypoleptinemia due to non-genetic causes such as anorexia nervosa and exercise leads to loss of reproductive function. Genetic/developmental factors influence the threshold required to turn off the behavioral, metabolic and endocrine responses to perceived caloric deprivation.

Journal Article↗
PubMed2006

Chikotsa--secrets, silence, and hiding: social risk and reproductive vulnerability in central Mozambique.

In this article, I examine pregnancy narratives and patterns of reproductive health seeking among women of fertile age in central Mozambique. I map the interplay between gendered economic marginalization, maternal risk perceptions, and pregnancy management strategies. By interpreting my data in light of Shona illness theories, I illuminate the ways that embodied experiences of reproductive vulnerability, risk perceptions, and social inequalities are linked: women attribute the most serious maternal complications to human- or spirit-induced reproductive threats of witchcraft and sorcery. This construction of reproductive vulnerability as social threats related to material and social competition significantly influences prenatal health seeking. Data reveal the structural and cognitive gap between biomedical constructions of risk and lay social threat perceptions. Plural health care systems are strategically utilized by women seeking to minimize both social and biological harm. On-the-ground ethnography shows that maternal health initiatives must take this plurality into full and accommodative account to achieve viable improvements in reproductive care and outcomes.

Adolescent↗
PubMed1994

Reproductive morphology and status of female Hawaiian monk seals (Monachus schauinslandi) fatally injured by adult male seals.

Female Hawaiian monk seals at Laysan Island in the Northwestern Hawaiian Islands seasonally risk aggressive mating attempts by groups of adult male monk seals. These attacks, which also target immature female and male seals at a lower frequency, result in injuries that are often fatal and are termed mobbings. This study was undertaken to assess the reproductive status of nine female seals that died after mobbing attacks and to obtain basic morphological data of reproductive tracts from ten females. Reproductive morphology of the seals indicated that the lengths of the uterine body and both uterine horns were significantly shorter in nulliparous than in parous seals. Seven of the nine seals were periovulatory, on the basis of gross morphology of the ovaries at death. The ovaries of the other two seals possessed immature follicles. Histological studies of the vagina and uterus confirmed the reproductive status of the seals. When the reproductive status at the time of first injury was estimated, all seals were in the follicular phase of the oestrous cycle. At least four of these seals were estimated to be in oestrus at the time of their first injury, and seven of the seals sustained at least one injury during the estimated period of oestrus (2-6 days). These results support the hypothesis that most adult female Hawaiian monk seals that die following an attack by male monk seals are periovulatory, and that the majority of the attacks occur during oestrus.

Animals↗
PubMed1994

Histomorphology, oLH and hCG receptors, and testosterone secretion in vitro in Rambouillet rams from lines in which females had been selected for low or high reproductive rate.

The objective of this study was to determine whether gross or histomorphological components of the testes, capacity and dissociation constants (Kd) of testicular oLH and hCG receptors, and gonadotrophin-stimulated testosterone secretion in vitro differed among Rambouillet rams from lines selected for low or high female reproductive rate and from rams of a random-bred control line. Lines had been selected for approximately 20 years. Data were collected from 22-month-old rams during the late breeding season. Rams among lines did not differ (P > 0.05) in gross testicular characteristics or most histomorphological characteristics. However, the percentage volume of interstitial vascular tissue was greater (P < 0.05) for rams from lines selected for low female reproductive rate than for rams from lines selected for high female reproductive rate. Receptor sites per Leydig cell and binding capacities of oLH and hCG receptors per testis, per gram of parenchyma, and per milligram of membrane protein did not differ (P > 0.05) among lines. The Kd values for oLH and hCG receptors did not differ (P > 0.05) among lines; however, receptor sites per Leydig cell, capacities of testicular parenchyma to bind gonadotrophin and Kd values were higher (P < 0.05) for oLH than for hCG receptors. Total oLH- and hCG-stimulated testosterone secretion in vitro did not differ (P < 0.05) among lines. In conclusion, selection for or against reproductive rate in Rambouillet ewes has not altered gross or most histomorphometric characteristics of the testes of male offspring, with the exception that selection against reproductive rate increased the proportion of testicular volume occupied by vascular tissue within the interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Effect of testosterone and cortisol administration on the reproductive tract of male Antechinus stuartii (Marsupialia).

The life history of Antechinus stuartii, a marsupial, is highly synchronized and culminates in a brief mating period that is followed by complete male mortality. The accessory reproductive tracts of male A. stuartii enlarge in association with testosterone and cortisol hormone concentrations, but this appears to be unrelated to the spermatogenic cycle. The present study examined the effects of testosterone and cortisol on the male reproductive tract. Four groups of adult males from May (when plasma testosterone and cortisol concentrations are low) were given depot injections of testosterone esters or synthetic cortisol in doses that mimic concentrations found in males in the breeding period (August). Males were given either saline, testosterone only, cortisol only, or testosterone plus cortisol. Experimental groups did not differ in the seminiferous tubule morphology. However, the cells from the caudal end of the epididymides of both testosterone groups were considerably hypertrophied compared with males treated with saline or cortisol only. Testosterone treatment significantly increased prostate and bulbourethral gland mass, although addition of cortisol to the testosterone administration diminished this effect. The morphology of the accessory reproductive tract of males treated with either saline or cortisol only was similar to that of untreated males at the same time of year, and the morphology of the accessory reproductive tract of males treated with testosterone plus cortisol was similar to that of untreated males in the breeding season. Like some other marsupials, the spermatogenic cycle in A. stuartii is apparently not correlated with androgen activity, while the accessory reproductive tract is affected by androgens.

Analysis of Variance↗
PubMed1999

Reproductive function in male rats with chronic nephrosis.

Endocrine dysfunction has been associated with renal diseases. The present study was conducted to explore reproductive function in male rats with chronic nephrosis. Experimental chronic nephrosis was induced by the administration of 7.5, 5.0 and 5.0 mg per 100 g body weight of puromycin aminonucleoside on days 0, 21 and 35, respectively. Reproductive function was evaluated on the basis of hormonal concentrations, mass of accessory sex organs and fertility during an 84 day period. Circulating LH, FSH, testosterone and oestradiol concentrations were measured by specific radioimmunoassays, while fertility was estimated by the rate of pregnancy induction. Samples were collected on days 7, 14, 28, 56 and 84. The results showed an important endocrine dysfunction characterized by low concentrations of LH and FSH during the first month, after which concentrations were similar to control values or even increased on days 56 and 84. Testosterone and oestradiol decreased significantly at all time points evaluated. The mass of the testes did not alter. However, the mass of the prostate and seminal vesicle decreased only during the first 2 weeks, and became essentially normal thereafter. The reproductive capacity of nephrotic males was eliminated on day 7, whereas on day 14, 16% of the group was able to mate successfully and subsequently most animals recovered their normal reproductive function. This study demonstrates for the first time that rats with experimental chronic nephrosis develop an important endocrine dysfunction, characterized mainly by persistent reduction in testosterone concentrations, which impairs reproductive capacity only transiently.

Animals↗
PubMed2004

Reproductive tissue selective actions of progesterone receptors.

The steroid hormone, progesterone, plays a central coordinate role in diverse events associated with female reproduction. In humans and other vertebrates, the biological activity of progesterone is mediated by modulation of the transcriptional activity of two progesterone receptors, PR-A and PR-B. These receptors arise from the same gene and exhibit both overlapping and distinct transcriptional activities in vitro. To delineate the individual roles of PR-A and PR-B in vivo, we have generated mouse models in which expression of a single PR isoform has been ablated. Analysis of the reproductive phenotypes of these mice has indicated that PR-A and PR-B mediate mostly distinct but partially overlapping reproductive responses to progesterone. While selective ablation of the PR-A protein (PR-A knockout mice, PRAKO mice) shows normal mammary gland response to progesterone but severe uterine hyperplasia and ovarian abnormalities, ablation of PR-B protein (PRBKO mice) does not affect biological responses of the ovary or uterus to progesterone but results in reduced pregnancy-associated mammary gland morphogenesis. The distinct tissue-specific reproductive responses to progesterone exhibited by these isoforms are due to regulation of distinct subsets of progesterone-dependent target genes by the individual PR isoforms. This review will summarize our current understanding of the selective contribution of PR isoforms to the cellular and molecular actions of progesterone in reproductive tissues.

Animals↗
PubMed2006

Neuroendocrine control of reproductive aging: roles of GnRH neurons.

The process of reproductive senescence in many female mammals, including humans, is characterized by a gradual transition from regular reproductive cycles to irregular cycles to eventual acyclicity, and ultimately a loss of fertility. In the present review, the role of the hypothalamic gonadotropin-releasing hormone (GnRH) neurons is considered in this context. GnRH neurons provide the primary driving force upon the other levels of the reproductive axis. With respect to aging, GnRH cells undergo changes in biosynthesis, processing and release of the GnRH decapeptide. GnRH neurons also exhibit morphologic and ultrastructural alterations that appear to underlie these biosynthetic properties. Thus, functional and morphologic changes in the GnRH neurosecretory system may play causal roles in the transition to acyclicity. In addition, GnRH neurons are regulated by numerous inputs from neurotransmitters, neuromodulators and glia. The relationship among GnRH cells and their inputs at the cell body (thereby affecting GnRH biosynthesis) and the neuroterminal (thereby affecting GnRH neurosecretion) is crucial to the function of the GnRH system, with age-related changes in these relationships contributing to the reproductive senescent process. Therefore, the aging hypothalamus is characterized by changes intrinsic to the GnRH cell, as well as its regulatory inputs, which summate to contribute to a loss of reproductive competence in aging females.

Adult↗

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