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PubMedDate not supplied

The Wilms tumor suppressor gene wt1 is required for development of the spleen.

The Wilms tumor suppressor gene WT1 (wt1 in mouse) is unique among tumor suppressors because, in addition to its involvement in cancer [1] [2] and various other diseases [3] [4] [5] [6], it has an essential role in the development of certain organs. This is revealed by the phenotype of mice with inactivated wt1 alleles [7]. These animals exhibit a complete failure of kidney and gonad development as well as abnormalities of the heart and mesothelial structures. On a C57BL/6 genetic background, wt1(-/-) animals die between day 13.5 (E13.5) and 15.5 (E15.5) of embryonic development [7]. We report here that crossing of the wt1 mutation onto different mouse backgrounds delayed embryonic lethality until birth. In wt1(-/-) mice on these different genetic backgrounds, we observed a dramatic failure of spleen development, in addition to the well characterized phenotypic abnormalities. The spleen anlage formed at around E12 to E13 and involuted by the E15 stage, before the invasion of hematopoietic cells. The absence of proper spleen development in these wt1(-/-) embryos correlated with enhanced apoptosis in the primordial spleen cells. The expression of hox11, a gene that also controls development of the spleen [8] [9], was not altered by the inactivation of wt1. In situ hybridization revealed that the two genes are regulated independently. These findings demonstrate that the penetrance of the wt1(-/-) phenotype depends on the existence of one or more modifier gene(s) and that wt1 plays a pivotal role in the development of the spleen, thereby extending its role in organogenesis.

Animals↗
PubMed2005

Seasonal changes in expression of LH-beta and FSH-beta in male and female three-spined stickleback, Gasterosteus aculeatus.

In teleost fishes, like in other vertebrates, the gonadal development is stimulated by two gonadotropic hormones; luteinizing hormone (LH) and follicle-stimulating hormone (FSH). To achieve a better understanding of the role of gonadotropins in teleost reproduction; expression of LH-beta and FSH-beta mRNA and the status of gonads and secondary sexual characters were analyzed over the annual cycle in male and female three-spined sticklebacks, a species in which the development of male secondary sexual characters and spermatogenesis are separated in time. The kidney in the male stickleback hypertrophies during the breeding season and produces a glue used when building nests. Kidney weights, as well as levels of 11-ketotestosterone (11KT), reached a peak in May. Both testosterone (T) levels and the gonadosomatic index (GSI, gonad weight/body weight x 100) in females started to increase in April, and peaked in May as well. Later in summer, after the breeding season, these features declined. In females, LH-beta expression followed the GSI and T levels closely, levels were low during winter and early spring, increased to a peak in late May and declined to low levels again in July. FSH-beta expression peaked earlier, in January and declined slowly over spring. In males, LH-beta expression peaked in May. During June-September, when spermatogenesis was active, LH-beta levels were very low. FSH-beta expression peaked in January, earlier than LH-beta expression did, and reached the lowest levels in July. Thus, when spermatogenesis started at the end of summer, the expression of both GTH-beta mRNAs, and circulating 11KT, displayed their lowest levels.

Animals↗
PubMed1990

[The influence of chemotherapy on testicular function of boys with acute lymphoblastic leukemia].

In order to investigate gonadal development of boys after chemotherapy, testicular biopsy specimens, which were obtained from 16 boys within 6 months after completion of the therapy for acute lymphoblastic leukemia, were assessed and their gonadal function was examined. More than half of them showed a decrease of Mean Tubular Diameter and Johnsen's Score Count, but no specimen showed a decrease of Tubular Fertility Index. Seventeen healed patients consisting of 12 biopsied and 5 non-biopsied cases were examined as to the volume of testis, development of the genital organ, skeletal age, plasma LH, FSH, testosterone, LH-RH test and HCG test. The period of follow-up after completion of chemotherapy varied from 1 month to 5 years. All patients showed testis volume, development of external genitalia and skeletal age suitable for their age. Some patients who were examined within 2 years after completion of chemotherapy, showed abnormal endocrine functions, but other patients examined after more than two years showed normal endocrine functions except a case who received testicular irradiation. Semen analysis in one case revealed density and motility within normal range. These data indicate that chemotherapy of acute lymphoblastic leukemia in boys damages testicular function, but more than 2 years later the spermatogenesis as well as endocrine function is expected to recover gradually.

Adolescent↗
PubMed1994

Dysgerminoma in a pure 45,X Turner syndrome: report of a case and review of the literature.

There is a high risk of neoplasm in dysgenetic gonads. Classically, in Turner syndrome, only patients with 45, X/46, XY mosaicism karyotype or with a fragment of Y chromosome (45, X+mar) are at risk of developing gonadal tumor. A case of a dysgerminoma arisen on the dysgenetic gonad of a 45, X Turner patient in the absence of Y chromosome material at cytogenetic and molecular biology analysis is reported. Five cases of gonadal tumor with a pure 45, X chromosome constitution have been previously reported in the literature. In these cases only cytogenetic analysis was performed. This is the first case of an ovarian tumor in a 45, X Turner syndrome in which the presence of Y material can be ruled out by an extensive molecular analysis of the blood and the tumor.

Adult↗
PubMed2000

Insulin-like growth factor receptors and their ligands in gonads of a hermaphroditic species, the gilthead seabream (Sparus aurata): expression and cellular localization.

Expression of insulin-like growth factor (IGF)-I, IGF-II, and IGF type I receptor (IGF-1R) genes was studied in gonads at different developmental stages of the protandrous hermaphroditic species the gilthead seabream (Sparus aurata) by reverse transcription-polymerase chain reaction and Northern blot analysis. Both IGF-I and IGF-II mRNA levels were highest in bisexual gonads and decreased during gonadal development. Regardless of the stage of gametogenesis, IGF-II mRNA levels exceeded those of IGF-I. Transcripts for IGF-1R RNA were detected in gonads at all stages studied. A major transcript of 11 kb was found in gonads and in gill arch and brain, but it was not found in liver and muscle. Distribution of the two types of IGF-1R and IGF-I in gonads was studied by immunohistochemistry. Immunoreactive IGF-I was found in the granulosa and theca cells of follicles at different vitellogenic stages and in oocytes at the chromatin-nucleolus and perinucleolus stage. In the testis, immunoreactive IGF-I was found in somatic cells of the cyst wall, interstitial cells, and spermatogonia A. In addition, IGF-1R was detected in the membrane of previtellogenic oocytes and in the theca and granulosa cells of vitellogenic and late vitellogenic follicles. In the testis, a positive reaction was identified in spermatogonia A and spermatids for the germ cells and in somatic cells of the cyst walls and interstitial cells. Local expression and production of IGFs and their receptors in fish gonads support a role for the IGF system in fish gonadal physiology.

Animals↗
PubMed2005

Patterns of proopiomelanotropin and proopiocortin gene expression and of immunohistochemistry for gonadotropin-releasing hormones (lGnRH-I and III) during the life cycle of a nonparasitic lamprey: relationship to this adult life history type.

There are two adult life history types among lamprey species, nonparasitic and parasitic, with the former commencing the final interval of sexual maturation immediately after metamorphosis. There are no extensive studies that directly compare hormone profiles during the life cycles of nonparasitic and parasitic lamprey species, yet such data may explain differences in development, reproductive maturation, and feeding status. The present study uses immunohistochemistry to show the life cycle profiles for gonadotropin-releasing hormones (GnRH-I and -III) in the brain of the nonparasitic species, the American brook lamprey, Lampetra appendix, for comparison with the extensive, published, immunohistochemical data on these hormones in the parasitic species, the sea lamprey, Petromyzon marinus. The complete cDNAs for the two lamprey prohormones, proopiocortin (POC), and proopiomelanotropin (POM), were cloned for L. appendix and both nucleotide and deduced amino acid sequences were compared with those previously published for P. marinus. The POC and POM cDNAs for both species were used in expression studies, with Northern blotting, throughout their life cycles. Although GnRH-I and -III immunohistochemistry revealed a similar distribution of immunoreactive cells and fibers in the two species during the life cycles, a qualitative evaluation of staining intensity in L. appendix, implied early activity in the brains of metamorphosis of this species, particularly in GnRH-I. GnRH-III seems to be important in larval life and early metamorphosis in both species. A novel feature of this immunohistochemical study is the monthly observations of the distribution and relative intensity of the two GnRHs during the critical period of final sexual maturation that lead to spawning and then the spent animal. L. appendix POC and POM nucleotide sequences had 92.9 and 94.6% identity, respectively, with P. marinus POC and POM and there was an earlier increase in their expression during metamorphosis and postmetamorphic life. Since there was some correlation between the timing of metamorphic development, gonad maturation, and brain irGnRH intensity with POC and POM expression in L. appendix, it was concluded that these prohormones yield posttranslational products that likely play a substantial role in development and maturation events that lead to the nonparasitic adult life history of this species.

Amino Acid Sequence↗
PubMedDate not supplied

Predisposing factors to autoimmune disease.

There are many factors that predispose women to autoimmune disease. The protective effect of testosterone during development prevents most males from getting autoimmune disease, although in some instances this protective effect can be bypassed by either genetic anomalies or endocrinopathies. Autoimmunity is defined as the development of symptoms and antibodies referable to one or another autoimmune disease. Some of the factors that predispose young women to autoimmunity also directly involve the endocrine system and indirectly, disorders of gonadal development. Altered sex steroid metabolism is one endogenous factor that predisposes a young woman to autoimmunity. The metabolism of estrone which can be directed to either the 16-or the 2-metabolites by diet, thyroid function, or certain drugs has a major influence on immune function and possibly gonadal pathology. Attempts to shift the metabolism of estrone to the 2-compounds with a variety of agents actually decreases the predisposition to autoimmunity. Other pre-disposing factors are all related to hormone metabolism and include hyperprolactinemia, the use of exogenous estrogenic agents, or compounds that change basic steroid metabolism. Most of these conditions are reversible.

Adolescent↗
PubMed1997

Isolation, characterization, and radioimmunoassay of Atlantic halibut somatolactin and plasma levels during stress and reproduction in flatfish.

Somatolactin (SL), a recently identified teleost pituitary hormone which is a member of the growth hormone/prolactin family, was isolated from pituitary tissue of Atlantic halibut (Hippoglossus hippoglossus). Pituitary proteins were extracted in ammonium bicarbonate (pH 7.8), fractionated using gel filtration chromatography, and purified using reversed-phase high-performance liquid chromatography. Halibut SL was identified on the basis of molecular size (determined by gel electrophoresis and mass spectroscopy), cross-reactivity of the putative hormone with antisera to cod SL, and N-terminal amino acid sequence. Polyclonal antibodies to purified halibut SL were raised in rabbits, and a radioimmunoassay (RIA) was developed for measurement of plasma concentrations of SL using purified halibut SL as a standard. The RIA was tested in several flatfish species including Pacific halibut (Hippoglossus stenolepis), English sole (Pleuronectes vetulus), and rock sole (Lepidopsetta bilineata). The assay was specific for SL as indicated by absence of cross-reactivity with Atlantic halibut growth hormone, prolactin, and GTH alpha subunit. Dilutions of plasma and pituitary extracts from Pacific halibut, English sole, and rock sole were parallel to the Atlantic halibut SL standard curve, indicating that the assay is valid for a range of flatfish species. Using halibut SL antiserum, SL was localized in the pars intermedia of English sole pituitary, where it has been identified in previously examined teleost species. The RIA was used to measure plasma levels of SL in Atlantic halibut and English sole during reproductive development, and in English sole subjected to various types of environmental stressors, including handling and crowding. In both sole and halibut, plasma SL concentrations remained relatively constant throughout gonadal development, but dropped during or following ovulation. Plasma SL levels in English sole tended to increase in response to acute stress, in parallel with plasma cortisol levels.

Amino Acid Sequence↗
PubMed2005

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis.

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5-12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5-15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5-12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.

Animals↗
PubMed1994

Histotypic in vitro reorganization of dissociated cells from mouse fetal gonads.

Cell suspensions obtained from the testes of 13.5-14.5 day post coitum (dpc) mouse embryos reaggregate in cord-like structures following in vitro culture for 24 h on a reconstituted basement membrane (Matrigel). Ovarian cells of the same fetal age or cell suspensions from sex indifferent gonadal ridges (11.5 dpc embryos) form an organized cell network but not cord-like structures. Antibodies directed against laminin or against the alpha 6 subunit of its integrin receptor prevent such morphogenetic processes. The addition of 5 micrograms/ml cycloheximide, cytochalasin B or tunicamycin also inhibits the phenomenon. Interestingly, compounds that increase intracellular cyclic AMP (cAMP) (dbcAMP, forskolin and isobutyl-1-methylxanthine) induce embryonic testicular cells to organize into structures similar to those assembled by ovarian or sex indifferent cell suspensions. These findings offer a simple in vitro model for studying some aspects of early gonad development and provide novel experimental evidence that cell motility and cell-cell adhesion, possibly regulated by cAMP dependent mechanisms, are likely to play an important role in gonad morphogenesis.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Influence of prenatal and postnatal photoperiods on postnatal testis development in the Siberian hamster (Phodopus sungorus).

In Siberian hamsters, juvenile testicular development is regulated to a large extent by photoperiod. Mother hamsters are able to pass photoperiodic information to their male fetuses, and this information can influence their postnatal gonadal development. In this study, we investigated the effects of gestation in long (16L:8D) and short (10L:14D) day lengths on the rates of juvenile testicular growth in several different postnatal photoperiods. On the day of parturition, parents and young from each gestation photoperiod were raised in 14L:10D through Day 13 of life and then were exposed to one of six photoperiods--16L:8D, 15L:9D, 14L:10D, 13L:11D, 12L:12D, or 10L:14D--until Day 32 of age. The data indicated that 15L and 14L are the minimal day lengths required to prevent complete inhibition of testis growth in long (16L) and short day (10L)-gestated hamsters, respectively. These results support earlier findings suggesting that gestation photoperiod can influence the rate of reproductive development in a certain range of "intermediate" postnatal day lengths (14L to 15L), but that gestation photoperiod does not alter the pattern of testis development in hamsters exposed to other (i.e., longer or shorter) postnatal photoperiods. Thus, both the absolute length and the direction of change of photoperiods experienced in early life can influence prepubertal testis growth.

Aging↗
PubMed1995

A quantitative investigation of gonadal feminization by diethylstilboestrol of genetically male embryos of the quail Coturnix coturnix japonica.

The effect of diethylstilboestrol on gonad development in quail embryos has been quantitatively analysed. Quail embryos at 4 days of incubation were treated with diethylstilboestrol (DES), using the egg dipping method. At 10 days of incubation, embryos were removed and killed by decapitation. Tissues were prepared for chromosome analysis, and the parts of the abdomen containing the gonads were prepared for serial sectioning and quantitative assessment. Left gonads of DES-treated male embryos resembled ovaries histologically, while their right gonads were markedly reduced in size. Right gonads of DES-treated female embryos were also further reduced by treatment with DES. There was no statistically significant effect by DES treatment on the size of left gonads, although the ratio of left compared with right gonadal volumes was highly significant. Since, in birds, the left embryonic gonad has ambisexual potential, while the potential of the right gonad is exclusively masculine, these results exemplify the adverse effect exerted by oestrogen on male sexual development in vertebrates.

Animals↗
PubMed2002

Invertebrates may not be so different after all.

Sex determination is widespread, but uses highly varied molecular mechanisms. A possible case of conservation between phyla is that of doublesex (dsx) from Drosophila and mab-3 (male abnormal 3) from Caenorhabditis elegans, genes related in sequence and some elements of function. mab-3 controls multiple aspects of male development, including sense organ formation in the tail and yolk transcription in the intestine, both similar to functions of dsx. Indeed, the male isoform of DSX can replace MAB-3 in C. elegans. Do related genes control sexual development in vertebrates, despite great differences in the biology of sex determination? We have identified several dsx-related genes in mouse and human. One, Dmrt1, appears to play a conserved role in vertebrate male gonad development. In humans, DMRT1 maps to a short interval required for testis differentiation. In all vertebrates examined, including mammals, birds, fish, and reptiles, Dmrt1 is expressed early in the genital ridge, in most cases with higher expression in future male gonads. A null mutation in murine Dmrt1 causes severe defects in testis differentiation, resembling those associated with human deletions removing the gene. Mutant females are unaffected. Other DM domain genes are expressed in embryonic gonad and are currently under study.

Animals↗
PubMed1999

Short day lengths affect perinatal development of the male reproductive system in the Siberian hamster, Phodopus sungorus.

The Siberian hamster, Phodopus sungorus, breeds seasonally. In the laboratory, seasonal breeding can be controlled by photoperiod, which affects the duration of nightly melatonin secretion. Winterlike, short day lengths induce gonadal regression in adult animals, and pups born and maintained in short days undergo pubertal gonadal development later than animals born into long days. However, to date there have been no reports of gestational photoperiod affecting fetal development of reproductive systems. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus (BC) and levator ani (LA), compose a sexually dimorphic, androgen-sensitive neuromuscular system involved in male reproduction. The SNB neuromuscular system was studied in male Siberian hamsters maintained from conception in short-day (8 h light, 16 h dark; 8L:16D) versus long-day (16L:8D) conditions. On the day of birth, and at postnatal (PN) days 2 and 18, the BC/LA muscles of hamsters gestated and raised in the short photoperiod were significantly reduced relative to those of their long-day counterparts. Testes weights were not significantly different between groups until day 18. Thus, photoperiod exposure during gestation and after birth affects perinatal development of the SNB system in this species, and these effects can be seen as early as the day of birth. Because photoperiod did not significantly affect testes weights until PN18, these results suggest that either perinatal photoperiod affects fetal androgen production without affecting testes weight or it influences BC/LA development independently from androgen.

Aging↗
PubMed2004

Impacts of 17beta-estradiol, including environmentally relevant concentrations, on reproduction after exposure during embryo-larval-, juvenile- and adult-life stages in zebrafish (Danio rerio).

Zebrafish (Danio rerio) were exposed for 3 weeks to low concentrations of estradiol including environmentally relevant concentrations (5, 25 and 100 ng/l), encompassing either their embryo-larvae (from fertilization to 21 day post-fertilization (dpf)), juvenile (from 21 to 42 dpf) or adult life stages (>200 dpf) with a view to investigating the most sensitive life stage of the zebrafish to 17beta-estradiol (E2). At all sampling points, whole-body vitellogenin concentrations and gonadal development were analyzed in order to investigate the effects of estrogen exposure on these endpoint in the zebrafish. In the adult stage, additional endpoints were measured including secondary sexual characteristics (manifestation of the uro-genital papillae (UGP) in males), gonadal growth (the gonado-somatic index (GSI)) and sex ratio. For all the different life stage exposures, reproductive performance of the F0 generation was assessed (egg production) and survival and development of the F1 embryo-larvae. Exposure to low concentrations of E2 resulted in vitellogenin induction whatever the life stage exposed but these effects were reversible after depuration. The effective concentration for vitellogenin induction in zebrafish early life stages was 100 ng E2/l, and in adult male zebrafish the effective concentration for vitellogenin induction (between 5 and 25 ng/l) was lower than for the early life stage fish. Exposure to E2 prior to (from fertilization to 21 dpf) and during the time of sex differentiation (from 21 to 42 dpf) also caused disruptions in the process of sexual differentiation (resulting in formation of a retrogonadal cavity in presumptive male, germ cell development and leading to a significant change of the sex ratio towards the female sex at the dose of 100 ng E2/l for the fish exposure as embryo-larvae) and altered patterns of egg production in the subsequent adults. Exposure of adult fish to E2 resulted in a modification of the secondary sexual characteristic in males at 25 and 100 ng E2/l as well as a dose-dependent inhibition of egg production. The findings from this study show that the nature and intensity of the reproductive effects of E2 are dependent of the time and concentration of exposures of zebrafish to E2, some of these effects being permanent (effect on the sexual differentiation) while others being reversible (effect on the Vtg induction). This study demonstrated that early life stages of zebrafish are sensitive to low concentrations of E2 and provides relevant data that could be used for the adaptation of existing fish early life stage test for the in vivo testing of estrogenic compounds. The data presented raise further concerns about the effects of steroid estrogens in the environment on fish reproductive health.

Age Factors↗
PubMed2005

Homozygous inactivation of Sox9 causes complete XY sex reversal in mice.

In the presence of the Y-chromosomal gene Sry, the bipotential mouse gonads develop as testes rather than as ovaries. The autosomal gene Sox9, a likely and possibly direct Sry target, can induce testis development in the absence of Sry. Sox9 is thus sufficient but not necessarily essential for testis induction. Mutational inactivation of one allele of SOX9/Sox9 causes sex reversal in humans but not in mice. Because Sox9(-/-) embryos die around Embryonic Day 11.5 (E11.5) at the onset of testicular morphogenesis, differentiation of the mutant XY gonad can be analyzed only ex vivo in organ culture. We have therefore conditionally inactivated both Sox9 alleles in the gonadal anlagen using the CRE/loxP recombination system, whereby CRE recombinase is under control of the cytokeratin 19 promoter. Analysis of resulting Sox9(-/-) XY gonads up to E15.5 reveals immediate, complete sex reversal, as shown by expression of the early ovary-specific markers Wnt4 and Foxl2 and by lack of testis cord and Leydig cell formation. Sry expression in mutant XY gonads indicates that downregulation of Wnt4 and Foxl2 is dependent on Sox9 rather than on Sry. Our results provide in vivo proof that, in contrast to the situation in humans, complete XY sex reversal in mice requires inactivation of both Sox9 alleles and that Sox9 is essential for testogenesis in mice.

Animals↗
PubMed1999

Steroidogenic factor-1: its role in endocrine organ development and differentiation.

The cloning of the first steroid hormone receptor over a decade ago provided vital insight into the mechanisms by which steroid hormones activate gene transcription. When bound by hormone, these receptors function as ligand-dependent transcription factors by binding to unique response elements in the promoter of specific target genes. Over 60 receptors have now been characterized in this superfamily of steroid receptors. Many receptors known as orphan receptors have been cloned by homology and have no known ligands but appear to be mediators of endocrine function in the adult and in many cases are essential developmental regulators in endocrine organogenesis. One such receptor is steroidogenic factor-1 (SF-1). While initially cloned as a transcriptional regulator of the various steroidogenic enzyme genes in the adrenal and gonad, it has become clear through genetic ablation experiments in mice that SF-1 is an essential factor in adrenal and gonadal development and for the proper functioning of the hypothalamic-pituitary-gonadal axis. In addition, these studies have revealed that SF-1 is necessary for the formation of the ventromedial nucleus of the hypothalamus. While we have learned much since the initial cloning of SF-1, the mechanisms by which SF-1 regulates these various developmental programs remain elusive. This article focuses on the characterization of SF-1 and its emerging role in endocrine homeostasis. Specific attention is placed on the mechanisms of action of this unique member of the nuclear receptor superfamily.

Animals↗
PubMed1992

Suppression of annual testicular development in Indian Palm squirrel, Funambulus pennanti by 8 hr temporal relationship of serotonin and dopamine precursor drugs.

Daily injections of 5-HTP (5-hydroxytryptophan, serotonin precursor) and L-DOPA (L-Dihydroxyphenylalanine, dopamine precursor) given 8 hour apart inhibited normal testicular growth in seasonally breeding Indian Palm Squirrel, Funambulus pennanti leading to complete gonadal atrophy, which was maintained till the end of the study. HCG administration induced higher degree of gonadal development but, when the two treatments (HCG + 8 hr relationship of 5-HTP and L-DOPA) were given simultaneously no significant difference was observed compared to control. Results indicate that induced suppression of gonadal function in a fashion similar to seasonal regression leading to non-breeding condition is the consequence of specific phase relationship (8 hr) between serotonergic and dopaminergic activities and not due to Serotonin or dopamine alone. This suggestion gets support from the finding that gonadal condition of squirrels receiving only 5-HTP (5-HTP control) or L-DOPA (DOPA control) was not different from control and exhibited normal testicular growth. It also seems that neurotransmitter precursor drugs given 8 hr apart possibly inhibited the activity of neuroendocrine-gonadal axis since this effect was overpowered by stimulatory effect of gonadotrophin. The findings strongly support the hypothesis that specific phase relation of circadian serotonergic and dopaminergic oscillations account for seasonal reproductive conditions.

5-Hydroxytryptophan↗