[Karyotype and histologic changes in anomalous gonadal development in man. I. Mixed gonadal dysgenesis].
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Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice.
Activin has numerous biological activities including regulation of follicular development, spermatogenesis, and steroidogenesis within the gonads. Activities of activin are regulated by follistatin (FST), an activin binding protein, and perhaps follistatin-like 3 (FSTL3; also known as FLRG and FSRP). FSTL3 is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FSTL3 is most highly expressed in the placenta and testis, whereas FST is highest in the ovary and kidney, suggesting that FSTL3 has biological actions that do not entirely overlap those of FST. To investigate the role of local FSTL3 as a potential regulator of activin action in gonad development and function, we examined FSTL3 expression in the mouse testis. FSTL3 protein was localized to Leydig cells, spermatagonia, and mature spermatids in normal male mice. We then created transgenic mice using a human FSTL3 cDNA driven by the mouse alpha-inhibin promoter. Three of five transgenic founders were fertile and were bred to establish lines. In the highest expressing line 3, transgene expression was largely restricted to gonads, with pituitary, adrenal, brain, and uterine expression being substantially lower. Gonad weights, sperm counts, and fertility were significantly reduced in transgenic males, and reduced litter size was evident in line 3 females. Within the testis, highest transgene expression was observed in Sertoli cells, and although most tubules showed evidence of normal spermatogenic development, degenerating tubules devoid of germ cells and Leydig cell hyperplasia were also evident in every line 3 animal examined. Ovaries from line 3 females contained fewer antral follicles and more apparent follicular atresia. Although circulating human FSTL3 levels were undetectable, FSH and LH levels in adult transgenic mice were not significantly different from wild-type animals. However, testosterone levels were significantly increased at d 21 and significantly reduced at d 60 compared with wild-type males. These results suggest that FSTL3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction.
Animals↗
Plasticity of gonadal development and protandry in fishes.
Sexual differentiation in eutherian mammals follows a simple governing paradigm: development proceeds in a female direction unless a masculinizing mechanism intervenes. Sexual development in fishes is much more plastic than in mammals. It permits the intervention of environmental factors and follows several different types of sequences that produce successive hermaphrodites and alternative pathways for the development of the same final sex. In spite of this plasticity, the primacy of female development is suggested by the initial ovarian phase in the development of gonads of both sexes in some gonochoristic fishes and by protogynous sex change. One barrier to the application of this principle to fishes generally is the existence of protandric hermaphrodites. Recent evidence suggests a reinterpretation of gonadal differentiation in a protandric anemonefish and a protandric sparid. In both cases, testicular development is both preceded and followed by ovarian development. These patterns are interpreted to mean that female development is primary and that male development is a temporary phase initiated by a masculinizing mechanism and terminated by its cessation.
Animals↗
Existence of an extra-retinal and extra-pineal photoreceptive organ that regulates photoperiodism in gonadal development of an Osmerid teleost, ayu (Plecoglossus altivelis).
Ayu (Plecoglossus altivelis) is an Osmerid teleost whose gonadal development exhibits clear photoperiodism: it is stimulated and prevented under short and long photoperiod, respectively. However, the photoreceptor organ involved in this process remains to be identified. In the present study, we examined whether gonads of ophthalmectomized (Ex) and pinealectomized (Px) ayu respond to short photoperiod to test whether photoreceptors other than lateral eyes and pineal complex are involved in the photoperiodic response of gonadal development. Gonadosomatic index (GSI) and plasma levels of sex steroids (testosterone and 11-ketotestosterone for males and testosterone and estradiol 17-beta for females) were significantly increased in the Ex+Px ayu kept under short photoperiod in both males and females as compared with the initial control. On the other hand, there were no significant increases in GSI and sex steroids in the Ex+Px ayu kept under long photoperiod. Histological observation of gonads in the Ex+Px ayu revealed that oocytes undergoing final maturation in females and proliferation of germ cells in males were observed under short photoperiod but not under long photoperiod. These results indicate that extra-retinal and extra-pineal photoreceptive organ regulates photoperiodic gonadal development in this species.
Animals↗
Gonadal development and sex differentiation in the cichlid fish Cichlasoma dimerus (Teleostei, Perciformes): a light- and electron-microscopic study.
Although the overall pattern and timing of gonadal sex differentiation have been established in a considerable number of teleosts, the ultrastructure of early stages of gonadal development is not well documented. In this study, gonads from larval and juvenile stages of laboratory-reared Cichlasoma dimerus were examined at the light-microscopic and ultrastructural levels. This freshwater species adapts easily to captivity and spawns with high frequency during 8 months of the year, providing an appropriate model for developmental studies. Larvae and juveniles were kept at a water temperature of 26.5 +/- 1 degrees C and a 12:12 hour photoperiod. Gonadal development was documented from 14-100 days postfertilization, covering the period of histologically discernible sex differentiation. Gonadal tissue was processed according to standard techniques for light and electron microscopy. C. dimerus, a perciform teleost, is classified as a differentiated gonochorist, in which an indifferent gonad develops directly into a testis or ovary. On day 14, the gonadal primordium consists of a few germ cells surrounded by enveloping somatic cells. Ovarian differentiation precedes testicular differentiation, as usual in teleost fishes. The earliest signs of differentiation, detected from day 42 onward, include the onset of meiotic activity in newly formed oocytes, which is soon accompanied by increased oogonial mitotic proliferation and the somatic reorganization of the presumptive ovary. The ovarian cavity is completely formed by day 65. Numerous follicles containing perinucleolar oocytes are observed by day 100. In contrast, signs of morphological differentiation in the presumptive testis are not observed until day 72. By day 100, the unrestricted lobular organization of the testis is evident. The latest stage of spermatogenesis observed by this time of testicular development is spermatocyte II.
Animals↗
Effects of trichostatin a, a histone deacetylase inhibitor, on mouse gonadal development in vitro.
Sry, Sox9 and M33 are thought to act as architectural transcription factors or as a chromatin regulator in gonadal development. However, the direct relationship between chromatin structure and sex determination has not yet been revealed. To clarify the effect of chromatin structural change on gonadal development, we examined the effects of trichostatin A, a histone deacetylase inhibitor, on mouse gonadal development in vitro. In the 0.1 microM treated testicular explants, the size of the gonad was significantly decreased, although the testicular cord formation occurred normally. In the 1.0 microM treated explants, the gonads revealed one or two large testicular cords. Sox9 and MIS expressions suggest that Sertoli cell differentiation is induced normally within the testicular cord, while Dnmt3b expression suggests that several immature Sertoli cells are located on the outside of the testicular cord. The 3beta-hsd expression indicates that Leydig cell differentiation occurs normally. On the other hand, germ cell loss was observed in the treated testicular explants. In the treated ovarian explants, the number of premeiotic germ cells was reduced without gonadal size change. Thus, trichostatin A affects the development of germ cells, but does not affect sex determination.
Animals↗
Sexually dimorphic expression of steroidogenic factor 1 (SF-1) in developing gonads of the American bullfrog, Rana catesbeiana.
Genetic sex determination leads to gonadal differentiation and ultimately the differences between the sexes in steroid hormone secretion. Gonadal steroidogenesis is critical for the development of a sexually dimorphic phenotype and adult reproductive function. Control of gonadal development and steroidogenesis is under the regulation, at least in part, of steroidogenic factor-1 (SF-1). We have begun to characterize SF-1 expression in an amphibian to determine the role of this protein in development and reproduction. We have detected a putative SF-1 protein from several tissues in the American bullfrog, Rana catesbeiana, that co-migrates with mouse SF-1 on a Western blot. Our results show that bullfrog SF-1 protein is expressed in steroidogenic and other reproductive tissues in a manner similar to that reported for other species, with high expression in the brain, pituitary, gonad, liver, and interrenal, but little or no expression in non-reproductive tissues such as skin and intestine. Using a quantitative Western blot analysis system, we documented changes in SF-1 protein in the gonads of developing tadpoles. Our results indicate that there is sexually dimorphic expression of SF-1 protein that becomes evident at the time of sexual differentiation of the gonads. In males, the expression of SF-1 decreases following testicular formation and in females the expression increases with the formation of ovaries. This is the first study to investigate changes in SF-1 during development at the protein level. The expression is similar to that reported for changes in SF-1 mRNA expression in chickens and alligators, however, opposite to that seen in mammals and turtles. These results indicate that SF-1 may play a pivotal role in development of the reproductive system in amphibians as it does in other vertebrate groups.
Animals↗
Expression of Dax-1 during gonadal development of the frog.
Dax-1, a member of the nuclear hormone receptor superfamily of transcription factors, is known to be involved in gonadal development in mammals. To date, Dax-1 has only been isolated in reptiles, birds and mammals. The expression of Dax-1 is down-regulated in the developing testis, but persists in the ovary of mice (Swain et al., Nat. Genet. 12 (1996) 404) and chicken (Smith et al., J. Mol. Endocrinol. 24 (2000) 23). Curiously, there is no sex difference in the expression patterns of Dax-1 in the American alligator (Western et al., Gene 241 (2000) 223). To understand its role(s) in gonadal development in vertebrates, molecular cloning of Dax-1 in amphibians is required. In this study, we cloned an amphibian Dax-1 homologue of the frog Rana rugosa and examined its expression profile during gonadal development. Cloned Dax-1 cDNA encoded a protein of 287 amino acids. Unlike mammalians that possess the three and one half repeat elements representing the putative DNA binding domain in the predicted sequence of Dax-1 protein, the frog had a single poorly conserved copy of the repeat unit. By RT-PCR analysis, the Dax-1 mRNA was detected in the liver and pancreas, but not in the testis and ovary of adult frogs. However, Dax-1 expression was seen first in the embryo at stage 12 and became stronger in tadpoles until stage X. The Dax-1 was transcribed in the testis stronger than in the ovary of frogs at stage XXV (just after completion of metamorphosis). In the gonad of frogs 2 months after metamorphosis (at this stage postmeiotic cells can be seen in the seminiferous tubules), the Dax-1 was expressed only in males. In addition, the Dax-1 transcription declined gradually as ovarian development proceeded, but its expression was down-regulated and then up-regulated rapidly when female-to-male sex reversal was caused by administration of testosterone into female tadpoles. Taken together, the results suggest that the Dax-1 may be closely involved in testicular development of amphibians.
Amino Acid Sequence↗
Expression levels of Mullerian-inhibiting substance, GATA4 and 17alpha-hydroxylase/17,20-lyase cytochrome P450 during embryonic gonadal development in two diverse breeds of swine.
Sexual differentiation and early embryonic/fetal gonad development is a tightly regulated process controlled by numerous endocrine and molecular signals. These signals ensure appropriate structural organization and subsequent development of gonads and accessory organs. Substantial differences exist in adult reproductive characteristics in Meishan (MS) and White Composite (WC) pig breeds. This study compared the timing of embryonic sexual differentiation in MS and WC pigs. Embryos/fetuses were evaluated on 26, 28, 30, 35, 40 and 50 days postcoitum (dpc). Gonadal differentiation was based on morphological criteria and on localization of GATA4, Mullerian-inhibiting substance (MIS) and 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450(c17)). The timing of testicular cord formation and functional differentiation of Sertoli and Leydig cells were similar between breeds. Levels of GATA4, MIS and P450(c17) proteins increased with advancing gestation, with greater levels of MIS and P450(c17) in testes of MS compared with WC embryos. Organization of ovarian medullary cords and formation of egg nests was evident at similar ages in both breeds; however, a greater number of MS compared with WC embryos exhibited signs of ovarian differentiation at 30 dpc. In summary, despite breed differences in MIS and P450(c17) levels in the testis, which may be related to Sertoli and Leydig cell function, the timing of testicular differentiation did not differ between breeds and is unlikely to impact reproductive performance in adult boars. In contrast, female MS embryos exhibited advanced ovarian differentiation compared with WC embryos which may be related to the earlier reproductive maturity observed in this breed.
Animals↗
Intrauterine gonadal development.
This review article summarizes the intrauterine gonadal development and differentiation of both male and female human embryos and fetuses. It describes in detail (1) the organization of the indifferent gonad and its seeding by the extra-gonadal germ cells, (2) the development of the duct systems before sex differentiation, and (3) the controlling mechanism of differentiation of the ovaries and testes. Timetable for the development of the human male and female reproductive systems have been compiled from the literature.
Animals↗
Unveiling the molecular basis of gonadal development: Multi-omics uncovers sex-related genes and steroid pathways in Sinonovacula constricta.
The razor clam Sinonovacula constricta is an economically important cultured mollusk in China, but the molecular mechanism of its gonadal development and sexual differentiation remains unclear. This study integrated gonadal transcriptomic, proteomic, and metabolomic analysis to identify key sex-related molecules. Transcriptome analysis identified 2795 DELs and 6497 DEGs between sexes, including the sex-related genes Fem-1b, Fem-1c, GUCY1B2 and FAT4, as well as a regulatory network of 39 lncRNA-mRNA pairs involving Tektin-4, Ropporin-1, Histone H1, and FoxN4. Proteomic analysis revealed 3217 DEPs: Tektin family members, Ropporin-1 and Tssk proteins were upregulated in the testis, while histone H1 and FAT4 were upregulated in the ovary. Metabolomic analysis detected 409 DEMs, with uridine identified as a potential sex differential marker (upregulated in the ovary), and 23 gonadal development-related DEMs showed sex-specific upregulation. Integrative transcriptome-proteome analysis identified 1543 co-expressed DEGs/DEPs enriched in nucleosome assembly, oxidative phosphorylation, and carbon metabolism, including key sex-related genes AKAP14, Tektin/Tssk families, Histone H1, and FAT4. Transcriptome-metabolome integration identified 32 shared KEGG pathways (e.g., biosynthesis of unsaturated fatty acids, pyrimidine metabolism), while proteome-metabolome integration revealed 5 (positive ion) and 6 (negative ion) co-enriched pathways, with alanine, aspartate and glutamate metabolism and oxidative phosphorylation being functionally relevant to gonadal development. Collectively, these results reveal the molecular basis of gonadal development, highlight critical sex-related genes and steroid metabolic pathways, and provide valuable resources for future reproduction and breeding in S. constricta.
Animals↗
Expression of follicle stimulating hormone-receptor mRNA during gonadal development.
Receptors for follicle-stimulating hormone (FSH) are found only in the gonads and have been localised to the Sertoli cells of the testis and the granulosa cells of the ovary. During gonadal development, functional signal transduction systems are present before gonadotrophin receptors appear indicating the expression of the receptors is the crucial step in development of gonadal responsiveness to gonadotrophins. The FSH receptor gene contains a single large exon which encodes the transmembrane and intracellular domains and nine smaller exons which encode most of the extracellular domain. In all species studied so far the FSH-receptor primary transcript has been shown to undergo alternate splicing. The function of these alternate transcripts is unclear but changes in alternate splicing appear to be associated with development of receptor mRNA expression. In the rat transcripts encoding only the extracellular domain of the receptor are detectable 2 days before transcripts encoding the full length receptor. In the mouse ovary FSH-receptor mRNA levels and alternate splicing has been measured during development. Results show that FSH-receptor mRNA is detectable in day 1 ovaries which contain only primordial follicles. At this stage mRNA levels are low but a significant increase in FSH-receptor mRNA is seen around day 5 when primary follicles first appear. This correlates with in situ hybridisation studies which first detect FSH-receptor transcripts in primary follicles. At all stages of development the level of transcripts encoding the extracellular domain was significantly greater than that encoding for the transmembrane and intracellular regions suggesting that significant levels of shortened transcripts are produced. In the hypogonadal (hpg) mouse which lacks circulating gonadotrophins levels of FSH-receptor mRNA appeared normal up to 15 days. This shows that gonadotrophins ar not require for development of FSH-receptor mRNA levels. Studies on FSH-receptor mRNA levels during granulosa cell luteinization show that there is complete loss of full-length transcripts soon after luteinization. Transcripts encoding the extracellular domain remain present, however, up to at least mid-cycle. Thus, changes in receptor transcript splicing during loss of FSH-receptors appear to mimic, in reverse, changes occurring during development. It may be that the FSH-receptor gene is constitutively expressed in follicular (pre-granulosa) cells, granulosa cells and granulosa-luteal cells but that control of RNA splicing regulates levels of full-length FSH-receptor transcript.
Animals↗
Battle of the sexes: new insights into genetic pathways of gonadal development.
Sex determination is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of gonadal development. Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal development provides an excellent opportunity to identify genes involved in differential organogenesis. The identification of the testis-determining gene, SRY (Sex-reversed on the Y), was a pivotal first step towards unraveling this genetic pathway. It is now clear that numerous other genes, in addition to SRY, are necessary for normal testis development. For example, human mutations in a variety of genes (SOX9, WT1, SF1) impair testis development. Murine models provide evidence for additional genes (Lhx9, Emx2, M33, Dmrt, Fgf9). This lecture will highlight insights gleaned from human mutations in the nuclear receptors, SF1 (Steroidogenic Factor1) (NR5A1) and DAX1 (Dosage-sensitive sex reversal, Adrenal hypoplasia congenita, X chromosome) (NR0B1). These studies reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans.
Adrenal Glands↗
Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Müllerian inhibiting substance promoter.
Mammalian gonadal development and sexual differentiation are complex processes that require the coordinated expression of a specific set of genes in a strict spatiotemporal manner. Although some of these genes have been identified, the molecular pathways, including transcription factors, that are critical for the early events of lineage commitment and sexual dimorphism, remain poorly understood. GATA-4, a member of the GATA family of transcription factors, is present in the gonads and may be a regulator of gonadal gene expression. We have analyzed the ontogeny of gonadal GATA-4 expression by immunohistochemistry. GATA-4 protein was detected as early as embryonic day 11.5 in the primitive gonads of both XX and XY mouse embryos. In both sexes, GATA-4 specifically marked the developing somatic cell lineages (Sertoli in testis and granulosa in ovary) but not primordial germ cells. Interestingly, abundant GATA-4 expression was maintained in Sertoli cells throughout embryonic development but was markedly down-regulated shortly after the histological differentiation of the ovary on embryonic day 13.5. This pattern of expression suggested that GATA-4 might be involved in early gonadal development and possibly sexual dimorphism. Consistent with this hypothesis, we found that the Müllerian inhibiting substance promoter which harbors a conserved GATA element is a downstream target for GATA-4. Thus, transcription factor GATA-4 may be a new factor in the cascade of regulators that control gonadal development and sex differentiation in mammals.
Animals↗
Effect of 17beta-estradiol, o,p'-DDT, octylphenol and p,p'-DDE on gonadal development and liver and kidney pathology in juvenile male summer flounder (Paralichthys dentatus).
The intent of this study was to compare histopathologically the effect of 17beta-estradiol (E(2)), o,p'-DDT, octylphenol and p,p'-DDE on gonadal development and liver and kidney condition in sexually immature (juvenile) summer flounder (Paralichthys dentatus). The dorsal sinus of 2-year-old juvenile male summer flounder was injected with the appropriate amount of chemical incorporated in coconut oil. A second identical injection was administered 2 weeks later. Fish were sampled at 4, 6 and 8 weeks after the initial injection and observed histopathologically. In control fish, spermatogenesis was predominantly in mid to late maturation. In fish treated with 1.0 and 10.0 mg/kg E(2) spermatogenesis regressed to primary spermatogonia or an immature functional state. Testicular atrophy and spermatogonial proliferation was also observed. An eosin-positive, hyaline material was found in the gonad, liver and kidney. This eosinophilic material also stained positive with Periodic Acid Schiff (PAS) stain. Treatment of 30 or 60 mg/kg o,p'-DDT elicited altered gonadal development similar to that observed with E(2) treated fish. Octylphenol treatment of 100 mg/kg resulted in reduced testicular size, ducts full of sperm, numerous spermatogonia and PAS positive material in the testis with no developing sperm cysts. No effect on liver or gonad tissues was observed with p,p'-DDE at the concentrations tested. All chemicals tested, with exception of p,p'-DDE, altered gonadal development, whereas only E(2) caused histopathological changes in the liver and kidney. Estrogenic activity induced the liver to produce a vitellogenin (VtG)-like substance and inhibited testicular maturation. As a result, both the lack of target cells for VtG and a continuous supply of VtG from the liver allowed the hyaline material to accumulate in the liver, testis and kidney causing histopathological changes.
Animals↗
Comparison of the gonadal development and plasma levels of sex steroid hormones in diploid and triploid sea bass, Dicentrarchus labrax L.
The goal of this study was to compare the reproductive physiology of triploid and diploid European sea bass (Dicentrarchus labrax L.). Gonads of diploid and triploid fish (males and females) were examined both microscopically and macroscopically, together with the plasma levels of the major sex steroids produced (testosterone and estradiol-17beta) when fish were adults. Prior to sexual maturation, the gonadosomatic index (GSI) of triploid males was similar to that of diploids. However, the GSI in 4-year-old adult triploid males was 1.8 times lower than that of diploids (P < 0.05). All diploid males exhibited normal gonadal development. In contrast, in triploid males spermatogenesis was impaired during late meiosis, affecting severely spermiogenesis. This was achieved by an increasing imbalance in the amount of DNA present in daughter cells of the same type as spermatogenesis progressed, as demonstrated by abnormal cell sizes, culminating in inviable spermatids. Thus, no spermiating triploid fish were observed during 4 years, which included three full consecutive maturation cycles. Furthermore, the germ cells from triploids were significantly larger than those from diploids (P < 0.001). Seasonal profiles of plasma levels of testosterone in 4-year-old males were essentially similar in both ploidies. On the other hand, triploid females had rudimentary ovaries containing oogonia and primary oocytes that were arrested during meiotic prophase I, while diploid females exhibited all stages of ovarian development. Diploid females showed levels of testosterone and estradiol-17beta significantly higher than those of triploids (P < 0.05), in which no endocrine signs of maturation were observed at all. Regarding sex ratios, triploids had 10% more females than diploids (P < 0.05) but in both ploidies males predominated, as is usually found in this species under culture conditions. These results show that triploidy blocked the initial phases of meiosis in females and the latter ones in males, resulting in the absence of or reduced gonadal development, respectively. In conclusion, we provide an explanation for the lack of gonadal development in triploid male fish, and, to the best of our knowledge, we report for the first time a case in which induced triploidy completely blocks meiosis in both sexes, thus conferring functional sterility in the sea bass.
Animals↗
The effects of nutrients in improving the depression of gonadal development in growing male rats kept under disturbed daily rhythm--investigations based on the L8(2(7)) type orthogonal array--.
The purpose of this experiment was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. Protein, methionine, vitamins, minerals and fat were selected as experimental factors, and eight kinds of diets were prepared based on the L8(2(7)) type orthogonal array. Dietary contents of the nutrients were normal (AIN-76 diet) or 1/3 to 1/2 of the normal content. Four-week-old rats (Fischer 344 strain) were kept under constant darkness for 4 wk. Control groups were kept under 12-h light/dark cycle. After 4 wk, the gonadal weights and serum testosterone content were evaluated. The effects of nutrients on gonadal development in rats differed between constant darkness groups (D-groups) and normal lighting groups (N-groups). Among the D-groups, the highest value for testes weight was observed under the normal protein, methionine added, low vitamin, low mineral and normal fat diet. The lowest value for testes weight was observed under the low protein, methionine added, normal vitamin, normal mineral and low fat diet. Among the N-groups, the highest value for testes weight was observed under the normal protein and no methionine diet, and the lowest value was observed under the low protein and no methionine diet. Among the D-groups, the highest value for serum testosterone was observed under the normal protein and low mineral diet. In the N-groups, serum testosterone was not affected by nutritional factors. It became clear that the amounts of protein, methionine, vitamins, minerals, and oil which are necessary for the gonadal development of growing male rats change when kept in constant darkness.
Animal Nutritional Physiological Phenomena↗
Continuous gonadotropin-releasing hormone infusion stimulates dramatic gonadal development in hypogonadal female mice.
Adult hypogonadal (hpg) mice, lacking GnRH, have infantile reproductive systems and levels of pituitary gonadotropins that are lower than normal. The mutant mice respond to brain grafts containing GnRH neurons with gonadal development and increased production of gonadotropins. In view of the substantial literature regarding the nature and necessity of pulsatile GnRH stimulation of gonadotropins, we were not surprised in earlier studies to find that the majority of hpg mice with successful grafts have pulsatile LH secretion. It is not known, however, why LH pulsatility was undetectable in some animals with significant gonadal development. The present experiment was intended to determine the degree to which hpg mice respond to continuous infusion of GnRH via osmotic minipumps. Unexpectedly, female hpg mice exhibited dramatic ovarian and uterine growth after 15 or 30 days of continuous exposure to GnRH, with five- and eightfold increases in ovarian and uterine weights, respectively. Despite evidence of increased gonadotropin secretion in the treated hpg mice, pituitary stores of FSH and LH remained low. Similar treatment of normal female mice for 15 days also depleted pituitary concentrations of LH and FSH without significantly altering gonadal weights or plasma gonadotropin levels. It is clear from the present that inferences of pulsatile GnRH secretion based on stimulation of gonadal development in hpg mice should be made with caution.
Animals↗