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Gonadal sex steroid hormones are well-studied modulators of reproductive physiology and behavior. Recent behavioral endocrinology research has focused on how the brain dynamically responds to - and may even produce - sex steroids, but the gonadal tissues that primarily release these hormones receive much less attention as a potential mediator of behavioral variation. This Commentary revisits mechanisms by which the reproductive hypothalamic-pituitary-gonadal (HPG) axis can be modulated specifically at the gonadal level. These mechanisms include those that may allow the gonad to be regulated independently of the HPG axis, such as receptors for non-HPG hormones, neural inputs and local production of conventional 'neuropeptides'. Here, I highlight studies that examine variation in these gonadal mechanisms in diverse taxa, with an emphasis on recent transcriptomic work. I then outline how future work can establish functional roles of gonadal mechanisms in reproductive behavior and evaluate gonad responsiveness to environmental cues. When integrated with neural mechanisms, further investigation of gonadal hormone regulation can yield new insight into the control and evolution of steroid-mediated traits, including behavior., Competing Interests: Competing interests The author declares no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Context: Testosterone (T) or estradiol (E2) are administered to suppress gonadal function in female-to-male (FTM) and male-to-female (MTF) transgender patients. How often sex steroids cause adequate suppression without GnRH agonist (GnRHa) or progestin therapy has not been reported., Objectives: (1) To determine how often T and E2 therapy alone can effectively suppress gonadal function in MTF and FTM transgender patients, and (2) to determine the frequency and range of serum E2 levels above the normal male range in FTM patients receiving T therapy., Design: Retrospective cohort study., Setting: Outpatient reproductive endocrinology clinic at an academic medical center., Patients: A total of 65 FTM and 33 MTF patients were included who were > 18 years of age and not receiving progestin or GnRHa therapy., Intervention: Female-to-male patients were receiving T through injections or gel. Male-to-female patients were receiving oral or subcutaneous E2., Main Outcome Measurements: In FTM patients the indicator of ovary suppression was amenorrhea. In MTF patients, the indicator of testes suppression was T levels <50 ng/dL., Results: Median serum total T level for FTM patients was 712 ng/dL (range, 370-1164 ng/dL). On T therapy alone, 90.8% of patients achieved amenorrhea and 49.2% of patients had serum E2 levels above the normal range for women. For MTF patients, the median serum E2 level was 129.2 pg/mL (range, 75-197 pg/mL). On E2 therapy alone, 84.8% of MTF patients had adequate suppression of testicular function., Conclusions: Testosterone and E2 therapy are usually effective without progestin or GnRHa therapy to suppress gonadal function in transgender patients. Progestin and/or GnRHa therapy should only be initiated in those patients who do not have adequate gonadal suppression on optimized doses of T or E2 alone., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cadmium (Cd) has been generally recognized as an endocrine-disrupting chemical for its toxic effects on the hypothalamus-pituitary-gonadal (HPG) axis accompanied by dysfunction in sex hormone secretion. Particularly, exposure to Cd during puberty versus post-puberty exhibits differing age-dependent effects that require further examination. This study sought to determine if cyanidin-3-O-glucoside (C3G), a typical anthocyanin with neuroprotective bioactivity, could protect against Cd-induced sex hormone-disorder in Pubertal male mice. C3G treatment reversed the disruption of hormone levels and increased Gnrh1 gene expression in the hypothalamus. In addition, the levels of gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), were reversed by C3G. Interestingly, C3G improved the expression of LH and FSH receptor in the testis in mice exposed to Cd. Furthermore, C3G activated the signaling pathway related to the synthesis of testosterone processing. In conclusion, C3G protected against Cd-induced dysfunction of sex hormone secretion through the regulation of the HPG axis in male mice during puberty. The results of this study suggest that consumption of anthocyanins can be protective against metal-induced male reproductive dysfunction., (Copyright © 2019. Published by Elsevier Ltd.)

In vertebrates, sexual differentiation of the reproductive system and brain is tightly orchestrated by organizational and activational effects of endogenous hormones. In mammals and birds, the organizational period is typified by a surge of sex hormones during differentiation of specific neural circuits; whereas activational effects are dependent upon later increases in these same hormones at sexual maturation. Depending on the reproductive organ or brain region, initial programming events may be modulated by androgens or require conversion of androgens to estrogens. The prevailing notion based upon findings in mammalian models is that male brain is sculpted to undergo masculinization and defeminization. In absence of these responses, the female brain develops. While timing of organizational and activational events vary across taxa, there are shared features. Further, exposure of different animal models to environmental chemicals such as xenoestrogens such as bisphenol A-BPA and ethinylestradiol-EE2, gestagens, and thyroid hormone disruptors, broadly classified as neuroendocrine disrupting chemicals (NED), during these critical periods may result in similar alterations in brain structure, function, and consequently, behaviors. Organizational effects of neuroendocrine systems in mammals and birds appear to be permanent, whereas teleost fish neuroendocrine systems exhibit plasticity. While there are fewer NED studies in amphibians and reptiles, data suggest that NED disrupt normal organizational-activational effects of endogenous hormones, although it remains to be determined if these disturbances are reversible. The aim of this review is to examine how various environmental chemicals may interrupt normal organizational and activational events in poikilothermic vertebrates. By altering such processes, these chemicals may affect reproductive health of an animal and result in compromised populations and ecosystem-level effects.

Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute of polybrominated diphenyl ethers (PBDEs). It has been frequently measured at concentrations of micrograms per liter (μg/L) in surface waters and waste water. However, limited information is available about the reproduction toxicology of TBOEP. In this study, adult zebrafish pairs were exposed to TBOEP at concentrations of 0, 5, 50, and 500μg/L for 21days. The effects on reproduction, hormone concentration, transcription of genes along the hypothalamic-pituitary-gonadal (HPG) axis, and gonadal development were investigated. After exposure to TBOEP, plasma concentrations of 17β-estradiol were significantly increased in both sexes of fish, while increase of testosterone was observed only in male fish. Transcription of genes along the HPG axis was significantly influenced by exposure to TBOEP in both male and female fish. Moreover, TBOEP decreases the average number of eggs production, as well as hatching success and survival rates in offspring. Histological examination shows inhibition of oocyte maturation in females and retardation spermiation in males, respectively. The results demonstrate that TBOEP could disturb the sex hormone balance by altering regulatory circuits of the HPG axis, affect gonadal development, eventually leading to disruption of reproductive performance and the development of progeny., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Plasma sex steroid hormonal profile and gonad histology were correlated to study the annual reproductive cycle of Hemibagrus nemurus. Hormones were measured by Enzyme Linked Immunosorbent Assay. Gonad tissues were observed by using light microscopy. The highest testosterone (T) value for male was observed in November and that of female was in October. 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels were highest in June and November, respectively. Hormonal profiles of T, 11-KT and E2 showed several peaks which indicated a non-seasonal pattern. There were significant differences (p < 0.05) in the monthly levels of T, 11-KT and E2. Gonadosomatic index of H. nemurus ranged from 1.14 ± 0.02 % to 7.06 ± 1.40 %, and high gonadosomatic indices were recorded in May, August and November. Gonad histology revealed that spermatozoa were always present in the testes which implied continuous spermatogenesis and asynchronous ovarian development pattern was observed in the ovaries. The annual reproductive cycle of H. nemurus did not show a seasonal pattern and this indicate that H. nemurus is a non-seasonal breeder with several spawning cycles and can be referred to as indeterminate batch spawner. The major significances of this study are annual sex steroid hormonal profile and asynchronous ovarian development of H. nemurus. This information will contribute to our knowledge of reproductive biology of H. nemurus.

Hermaphrodites have both sexes during their life, including an initial primary sex determination and in later stage maintenance one of the sexual fates (secondary sex determination). Sex change (secondary sex determination) occurs in animals, but it is lost in amphibians through, mammals in vertebrates. Teleosts have various strategies and mechanisms of sex determination including genetic and environmental cues. However, the mechanisms by which the cues guide sex change are complicated in fish. This manuscript reviews our understanding of these processes in protandrous black porgy at the gonadal and neuroendocrine levels. Our studies addressed the process of sex change through brain-pituitary-gonad axis, and then secondary sex determination was switched by the fate of testis.

The sex steroid hormones testosterone and estrogen are essential determinants not only of reproductive functions but also for bone growth and the maintenance of skeletal integrity. The importance of this latter form of regulation is best exemplified by the fact that gonadal failure triggers bone loss in both genders and causes osteoporosis in postmenauposal women. Traditionally, bone physiology is studied with the view that the skeleton is simply a recipient of hormonal inputs. However, a richer picture of bone physiology has recently emerged, and it is now clear that the skeleton is an endocrine organ itself. This is particularly relevant to the interplay between bone and gonads because genetics and biochemical evidence have established that bone, via the osteoblast-derived hormone osteocalcin, promotes testosterone biosynthesis. This review will present the mechanism of action of osteocalcin and will discuss the implications of this novel regulation., (© 2012 New York Academy of Sciences.)

It has long been known that sex steroid hormones regulate bone mass accrual. This observation raises the testable hypothesis that bone may in turn regulate the synthesis and secretion of sex steroid hormones in one or both genders. This hypothesis is comprised within a more general hypothesis that bone mass, energy metabolism, and reproduction are regulated coordinately. The identification of osteocalcin as an osteoblast-specific secreted molecule allows us to address this question in molecular terms. This review details how the regulation of male fertility by osteocalcin was unraveled, and how osteocalcin signaling in Leydig cells of the testis occurs. It also discusses the implication of this novel mode of regulation of testosterone synthesis observed in males but not in females.

Plasma levels of testosterone (T), 17-β-estradiol (E2), progesterone (P4), dehydroepiandrosterone (DHEA), corticosterone (B), thyroxine (T4) and triiodothyronine (T3) were monitored during postnuptial and the prenuptial molt in domestic goose (Anser anser domesticus) in both sexes. 1. At the beginning of postnuptial molt (when the old, worn dawny-, and cover feathers' loss starts) in ganders, the levels of T, E2, P4 decrease while DHEA and B significantly increase. The elevated levels of T4 and low T3 concentrations characteristic of the last phase of the reproduction, remain unchanged. In layers, similar changes were observed, however, B decreases. 2. In the early phase of outgrowth of wing and cover feathers, plasma levels of T, E2 and P4 are low. Elevated B, DHEA and T4 concentrations decrease in ganders, while in layers DHEA increases and B and T4 levels remain unchanged. T3 increases in both sexes. 3. The subsequent intensive outgrowth period of wing- and cover feathers both in ganders and in layers is characterized by very low levels of T, E2, DHEA and T4, but P4 increased, and T3 concentration remain high. 4. At the end of postnuptial molt - when the outgrowth of dawny, cover-, and wing feathers stops - very low T, E2, P4, DHEA and T4 levels and and high T3 plasma levels were found in both sexes. Fast increase of plasma B was detected in ganders, while in geese, B concentration remain high. 5. During prenuptial molting (outgrowth of contour and tail feathers) low E2, P4 and T4, increasing T and DHEA, but very high T3 and B plasma concentration were measured in ganders. In layers, very low T, E2, P4, DHEA and T4 levels, and very high B and T3 levels were found. 6. At the beginning of the fall-winter sexual repose (postmolting stage) T, E2, P4, DHEA and T4 levels increase, T3 and B declines in both sexes. 7. In the subsequent phase of fall-winter period (preparatory stage) there is a further increase in T, P4 and T4, a fast increase of B and a decrease of E2, DHEA and T3 in ganders. In layers, T, P4 and DHEA decrease, B increases and the T4 and T3 do not change. 8. At the beginning of reproduction high T level, unchanged DHEA, slightly declined P4, and decreased E2, T4, T3 and a strong decline of B concentrations occur in ganders. In layers, T is further increased, E2 and P4 shows high levels, and, at the same time DHEA and T3 remain unchanged, while B and T4 decrease.

Neurogenesis in the adult songbird brain occurs along the ventricular zone (VZ), a specialized cell layer surrounding the lateral ventricles. To examine the acute effects of sex steroids on VZ cell proliferation, male and female adult zebra finch brain slices containing the VZ were exposed to 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) in vitro. Slices from one hemisphere served as the control, while contralateral slices were treated with steroids, steroidogenic enzyme inhibitors or gonadal tissue itself. There were no significant effects on VZ cell proliferation in either sexes by acute exposure to 17beta-estradiol (E2), dihydrotestosterone (DHT), a cocktail of four sex steroids, and inhibitors of sex steroid synthesis (aminoglutethimide, ketoconazole, and fadrozole), or by activation of a mitochondrial cholesterol transporter. By contrast, dehydroepiandrosterone (DHEA) suppressed VZ cell proliferation in males, but not females, replicating previous observations involving treatments with corticosterone and RU-486. This suggests that DHEA suppresses proliferation in males via a glucocorticoid receptor-related mechanism. These results suggest that neurosteroidogenesis per se has little effect on acute VZ cell proliferation. Co-incubation with an ovary of female, but not male, slices significantly increased VZ cell proliferation; testicular tissue had no impact on proliferation in males or females. This suggests a role for a non-steroidal ovarian factor on adult female VZ cell proliferation. We also have evidence that previously reported sex-differences in BrdU-labeling along the adult VZ (males>females) result from a more rapid loss of cells in females. Sex differences in steroid action and cell death along the VZ may contribute to the maintenance of the sexually dimorphic song system., (2010 Elsevier B.V. All rights reserved.)

In many vertebrate species, sex is determined at fertilization of zygotes by sex chromosome composition, knows as genotypic sex determination (GSD). But in some species-fish, amphibians and reptiles-sex is determined by environmental factors; in particular by temperature-dependent sex determination (TSD). However, little is known about the mechanisms involved in TSD and GSD. How does TSD differ from GSD? As is well known, genes that activated downstream of sex-determining genes are conserved throughout all classes of vertebrates. What is the main factor that determines sex, then? Sex steroids can reverse sex of several species of vertebrate; estrogens induce the male-to-female sex-reversal, whereas androgens do the female-to-male sex-reversal. For such sex-reversal, a functioning sex-determining gene is not required. However, in R. rugosa CYP19 (P450 aromatase) is expressed at high levels in indifferent gonads before phenotypic sex determination, and the gene is also active in the bipotential gonad of females before sex determination. Thus, we may predict that an unknown factor, a common transcription factor locates on the X and/or W chromosome, intervenes directly or indirectly in the transcriptional up-regulation of the CYP19 gene for feminization in species of vertebrates with both TSD and GSD. Similarly, an unknown factor on the Z and/or Y chromosome probably intervenes directly or indirectly in the regulation of androgen biosynthesis for masculinization. In both cases, a sex-determining gene is not always necessary for sex determination. Taken together, sex steroids may be the key-factor for sex determination in some species of vertebrates., ((c) 2010 Wiley-Liss, Inc.)

A normal rate for the linear growth of a child or adolescent is a strong statement for the good general health of that child. Normal growth during childhood is primarily dependent on adequate nutrition, an adequate psychosocial environment, the absence of disease and adequate amounts thyroid hormone and growth hormone (and its downstream product, IGF-1). At adolescence there is the reawakening of the hypothalamic-pituitary-gonadal axis and its interaction with the GH/IGF-1 axis to subserve the pubertal growth spurt. The fat tissue-derived hormone, leptin and its receptor are likely involved in at least two aspects of pubertal development - sexual development itself and the alterations in body composition including the regional distribution of fat and bone mineralization. During the prepubertal years the male female differences in body composition are quite modest, but change remarkably during pubertal development with boys showing a relative decrement in fat percentage and girls a marked increase in concert with rising levels of circulating leptin. The boys show a much greater increase in lean body tissue and the relative proportions of water, muscle and bone. These may be observed as the differential growth of the shoulders and hips. The net effect of these pubertal changes is that the young adult woman has approximately 25% body fat in the 'gynoid' distribution while the male has much more muscle, especially in the shoulders and upper body but only approximately 13% body fat., (Copyright 2010 S. Karger AG, Basel.)

The present study determines how populations of Great Tits (Parus major) breeding in southern, mid and northern European latitudes have adjusted their reproductive endocrinology to differences in the ambient temperature during the gonadal cycle. A study based on long-term breeding data, using the Colwell predictability model, showed that the start of the breeding season has a high predictability ( approximately 0.8-0.9) at all latitudes, and that the environmental information factor (I(e)) progressively decreased from mid Italy (I(e)>4) to northern Finland (I(e)<1). The results indicate that integration of supplementary information, such as ambient temperature, with photoperiodic initial predictive information (day length), becomes progressively more important in maintaining the predictability of the breeding season with decreasing latitude. This hypothesis was verified by exposing photosensitive Great Tits from northern Norway, southern Sweden and northern Italy to sub-maximal photo-stimulatory day lengths (13L:11D) under two different ambient temperature regimes (+4 degrees C and +20 degrees C). Changes in testicular size, plasma levels of LH and testosterone were measured. The main results were: (1) Initial testicular growth rate, as well as LH secretion, was affected by temperature in the Italian, but not in birds from the two Scandinavian populations. (2) Maximum testicular size, maximum LH and testosterone levels were maintained for a progressively shorter period of time with increasing latitude, regardless of whether the birds were kept on a low or a high ambient temperature. (3) In birds from all latitudes, the development of photorefractoriness, as indicated by testicular regression and a decrease in plasma levels of LH and testosterone, started much earlier (with the exception for LH Great Tits from northern Scandinavia) when kept on +20 degrees C than when kept on +4 degrees C. The prolonging effects of a low temperature was more pronounced in Mediterranean birds, than in birds from Scandinavia, and more pronounced in Great Tits from southern Scandinavia than in Great Tits from northern Scandinavia. Ecological implications of the results are discussed, as well as possible impact of global warming on the breeding success of European Great Tits from different breeding latitudes.

Hormonal control systems are complex in design and well integrated. Concern has been raised that these systems might act as evolutionary constraints when animals are subject to anthropogenic environmental change. Three systems are examined in vertebrates, especially birds, that are important for assessing this possibility: (i) the hypothalamic-pituitary-gonadal (HPG) axis, (ii) the activational effects of sex steroids on mating effort behaviour, and (iii) sexual differentiation. Consideration of how these systems actually work that takes adequate account of the brain's role and mechanisms suggests that the first two are unlikely to be impediments to evolution. The neural and molecular networks that regulate the HPG provide both phenotypic and evolutionary flexibility, and rapid evolutionary responses to selection have been documented in several species. The neuroendocrine and molecular cascades for behaviour provide many avenues for evolutionary change without requiring a change in peripheral hormone levels. Sexual differentiation has some potential to be a source of evolutionary inertia in birds and could contribute to the lack of diversity in certain reproductive (including life history) traits. It is unclear, however, whether that lack of diversity would impede adaptation to rapid environmental change given the role of behavioural flexibility in avian reproduction.

Variation in the production of the plasma steroid hormones E(2), 17alpha-OHP and T in females and T and 11-KT in males, was investigated in the mudskipper Boleophthalmus pectinirostris during the spawning season. Females with oocytes at the vitellogenic stage (GSI 5.97-6.86%) and mature males with GSI of 0.255-0.288% were collected at intervals of 3-4 days within the two complete semilunar cycles from May 31 to June 30, 2006. The results showed that variations in the levels of plasma steroid hormones were synchronized obviously with semilunar periodicity in both females and males. Each steroid hormone level exhibited two cycles, each cycle with a peak. In females, the first peaks in plasma E(2), 17alpha-OHP and T levels were observed 3 days after the first lunar quarter, and the second ones, 4 days after the last lunar quarter. In males, the first peaks of plasma T and 11-KT levels occurred 3 days after the first lunar quarter, and the second ones, at the last lunar quarter. The fact that, in the present study, changes in the levels of plasma steroid hormones were synchronized with semilunar periodicity, although the fish were at the same stages of gonadal development, suggests that variation of plasma steroid hormones is basically regulated by biological rhythms (Zeitgebers), and that tidal movement (with its semilunar periodicity) is the major environmental factor stimulating steroid hormone production in B. pectinirostris.

Maturation of the reproductive system during puberty results in elevated levels of gonadal steroid hormones. These hormones sculpt neural circuits during adolescence, a time of dramatic rewiring of the nervous system. Here, we review the evidence that steroid-dependent organization of the adolescent brain programs a variety of adult behaviors in animals and humans. Converging lines of evidence indicate that adolescence may be a sensitive period for steroid-dependent brain organization and that variation in the timing of interactions between the hormones of puberty and the adolescent brain leads to individual differences in adult behavior and risk of sex-biased psychopathologies.

The impact of sirolimus on hormone levels involved in the hypothalamus-pituitary-gonad axis in male heart transplant recipients was investigated. A pair-matched analysis with 132 male heart transplant recipients on either sirolimus based- or calcineurin inhibitor-based immunosuppression was performed. Matching criteria were age, years after transplantation and creatinine levels. Measured parameters were testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sexual hormone-binding globulin (SHBG) and free androgen index (FAI). Mean testosterone was 3.86 +/- 1.41 ng/mL in the sirolimus group and 4.55 +/- 1.94 ng/mL in the controls (p = 0.025). Serum LH was 12.82 +/- 11.19 mlU/mL in the sirolimus patients and 6.2 +/- 5.25 mlU/mL in the controls (p = 0.015). Follicle stimulating hormone levels were 13.31 +/- 18.4 mlU/mL vs. 7.32 +/- 5.53 mlU/mL, respectively (p = 0.015). The analysis revealed a significant decrease in testosterone and a significant increase in FSH and LH in the sirolimus group. The duration of sirolimus treatment correlated positively with SHBG (p < 0.01), LH (p < 0.05) and FSH (p < 0.05) and negative with the FAI (p < 0.05). Sirolimus trough levels correlated with LH and FSH levels (p < 0.01). Heart transplant recipients treated with sirolimus revealed significantly lower testosterone levels and a significant increase in gonadotropic hormones. These effects were trough-level dependent. All candidates awaiting organ transplantation should be informed about these adverse effects.

Objective and Design: The effects of sex, sex hormones and gonads were studied in dogs because men secrete more acid than woman and duodenal ulcer is commoner in men and remits in pregnancy and after stilboestrol., Material: Four male and 4 female greyhounds with chronic gastric fistulas were tested., Methods: Histamine was infused i.v. 1-16 micrograms/min and plateau acid output measured in the last 30 min of each 60 min infusion., Treatment: The gonads were then removed and secretion retested. The orchidectomised dogs were then given stilboestrol 2 mg daily (+/-progesterone 25 mg i.m. three times a week) and the oophorectomised bitches given testosterone propionate 25 mg twice weekly i.m. and secretion again retested., Results: Submaximal and maximal acid outputs (and serum pepsinogen) of dogs and bitches were similar and correlated with body weight. Gonadectomy did not alter these functions nor did hormones of the opposite sex given for 1-12 months., Conclusions: In the dog, as in the rat, and probably in man, histamine-stimulated gastric acid output is a function of body size and not of sex.

Profiles of testosterone, 11-ketotestosterone, androstenedione, and estradiol were determined by RIA, and immunocytochemical techniques were employed to identify gonadotropin (GTH) I and II and gonadotropin releasing hormone (GnRH) in monosex and mixed sex populations of rainbow trout from 1 to 126 days postfertilization (dpf). Steroid levels were relatively high at 1 dpf and declined until 25 dpf. At 30 and 48 dpf (hatching) steroid levels increased slightly before they fell by 78 dpf and remained relatively constant thereafter. Trends toward differences in steroid content between males and females became evident around the time gonadal differentiation was histologically discernible (78 and 90 dpf). GTH I was present in the proximal pars distalis at all dates (48-126 dpf), whereas GTH II was not detectable. GnRH was found at all dates (48-126 dpf) and was distributed in several areas of the brain including the nucleus preopticus periventricularis, nucleus lateralis tuberis, and the pituitary in the region where GTH I was found. No differences were seen between males and females in the timing of appearance, localization, or intensity of staining of these peptide hormones. Given that the brain-pituitary-gonadal axis seems to be intact during the process of sexual differentiation and the fluctuations of steroid levels during this process, sex steroids may play the driving role for sexual differentiation of rainbow trout.

The growing body of evidence, both experimental and clinical supports the concept of multiplicity of endocrine-immunological interactions. Such interrelationship should be viewed as bidirectional: the immune system like other homeostatic mechanisms is subject to regulation by endocrine factors, while vice versa the immune system by itself affects the function of the neuroendocrine system. The gonadal steroids influence immunity acting at two levels: at the level of primary lymphoid tissues or mature immunocompetent cells, and at the level of the hypothalamo-pituitary axis, influencing the release of hormones which by itself also have immunoregulatory properties. Studies indicate that antiestrogens also affect immune response in both agonistic and antagonistic mode of action, especially analyzed in patients with endocrine-responsive tumors related by hormone therapy.

Lipid metabolism takes place in the Golgi apparatus, but at a higher rate in female than in male rats. I therefore examined the Golgi apparatus by morphometric means for differences between the sexes at the light- and electron-microscopic level. The Golgi apparatus was stained in situ by a zinc-iodide-osmium method. The counts of the Golgi apparatus in cross-sections in female hepatocytes by light microscopy were approximately twice that in male hepatocytes. Upon ovariectomy, these counts were greatly reduced but were reestablished after estrogen supplement. To clarify this phenomenon, three-dimensional reconstructions of the Golgi apparatus were produced from electron-microscopic images of serially cut 160-nm sections. The Golgi apparatus of both male and ovariectomized females had the shape of a small ring, whereas it took the form of a large elongated cylinder in normal females and in castrated males after treatment with estrogen. The numerical difference in Golgi apparatus counts by light microscopy of in males and females is, therefore, apparently attributable to the size and shape of the Golgi apparatus, and is controlled by the estrogen level.

Exposure of juvenile minks to artificial light conditions imitating early autumn (additional illumination from 20 June to 20 July followed by 8 h daylight from 21 July to 10 October--photoperiod I; 8 h daylight from 21 July to 10 October--photoperiod II) induced the prolonged modification of sex steroid concentrations. The increase in plasma testosterone concentrations during the prepubertal period was followed by a decrease before and during the mating period in experimental males. The concentration of oestradiol in plasma increased just before the start of the mating period (January and February) in females under photoperiod I, and these hormonal changes were accompanied by an increase in fertility. The conditions of photoperiod II (involving fewer hours of daylight) had less effect on the sex steroid concentration in the blood of females, and fertility was not changed. The response of gonads to hCG injection at the beginning of puberty (November) was higher in males exposed to photoperiod I conditions and in females exposed to both photoperiods than in control animals.

During puberty, the growth spurt and stage of pubertal maturation are two processes intimately related both being dependent on the combined action of growth hormone (GH) and sex steroids. While it is well established that both GH and sex steroids are required for a pubertal growth spurt, the precise role played by GH on the timing of onset and rate of progression through different stages of pubertal maturation is not entirely clear. A better understanding of the involved physiologic mechanisms will help clinicians in the management of adolescents with growth and/or pubertal disorders.

1. Sternopygus macrurus were collected in Venezuela during the period of gonadal recrudescence in early or late dry season. Electric organ discharge (EOD) frequencies were recorded, blood samples were taken for analysis of steroid titers, and gonads were taken for determination of reproductive condition. 2. Mean EOD frequencies were significantly lower in males than in females in all samples. EOD frequency was inversely correlated with body length in males in late, but not early, dry season, and these parameters were never correlated in females. 3. Plasma levels of testosterone (T) and 11-ketotestosterone (11-KT), but not estradiol-17 beta (E2), were inversely correlated with EOD frequency in males. No 11-KT was observed in plasma of females, and plasma levels of T and E2 in females were comparable to those of males. Neither T nor E2 were correlated with EOD frequency in females. 4. Testes collected in late dry season were more mature than those from early dry season; androgen levels and EOD frequency were correlated with testicular maturity. Ovaries collected in early dry season were immature, while those from late dry season were more mature. There was no relationship between EOD frequency and stage of ovarian development. 5. These results suggest that plasma androgens modulate EOD frequency in males during the reproductive season and that plasma E2 has little relationship to EOD frequency in either sex.

The endocrine events that we recognize as adolescent puberty actually begin early in fetal life. The natural history of these developments and the "switches" that turn them on and off are reviewed in terms of both normal and abnormal maturation of sexual function and are related to potential therapeutic approaches. A major focus is on the observation that adrenarche and gonadarche are totally independent events.

Mature male and female mice 50 days of age were challenged with i.v. sodium arachidonate at doses of 12.5, 25, 50 and 100 mg/kg. A dose-dependent response in terms of mortality was observed. Males were significantly more susceptible to arachidonate-induced mortality than females at the 25 and 50 mg/kg doses (P less than .05). The 100 mg/kg dose produced 100% mortality in both sexes. When mice aged 23, 29, 35 and 50 days were challenged with 50 mg/kg of arachidonate, no gender difference was observed until mice were 35 days of age, at which time the male mortality was 80%, compared to 57% for female mice (P less than .05). Mice gonadectomized at 23 days and intact mice 23 days of age were treated with s.c. estradiol, testosterone or vehicle for 7 days before arachidonate challenge. Among these groups, the gonadectomized females and intact males were significantly protected by estradiol when compared to the appropriate controls (P less than .05). In contrast, testosterone pretreatment had no significant effect on mortality. These results demonstrate that the development of the gender difference in arachidonate-induced mortality in mice is dependent upon the presence of gonadal hormones in the immature stages.

Gonadal homogenates of rainbow trout from D(ay) 60, D100 and D200 after fertilization have been incubated in vitro in the presence of dehydroepiandrosterone-3H to demonstrate 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and delta 5,4-isomerase activity, of pregnenolone-3H to assess the synthesis of "progestins" and of androstenedione-3H to determine oestrogen synthesis in the ovaries and the formation of androgens in the testes. Histologically indifferent gonads from D50 contained 3 beta-HSD, delta 5,4-isomerase and 17 alpha-hydroxylase, indicating a capacity to synthesize progestins. Ovaries from D100 possessed the same enzymes as D50 gonads; those from D200 had, in addition, 17 beta-HSD and aromatase, indicative of oestrogen synthesis. Unlike the D50 gonads, the D100 testes also contained 17 alpha, 20-desmolase and 11 beta-hydroxylase, showing a capacity to synthesize androgens. 17 beta-HSD was only demonstrated in D200 testes. The possible role of androgens and progestins in the regulation of gonadal sex differentiation in rainbow trout has been discussed. Ultrastructural and enzymecytochemical investigations have demonstrated stroma (Leydig) cells as sources of steroidogenesis in rainbow trout testis from D100 onwards. The appearance of big mitochondria with many tubular cristae in those cells synchronized with the appearance of 11 beta-hydroxylase activity. Obvious steroidogenic sites could not be demonstrated in younger gonads and developing ovaries.

When autumn-spawning bitterling, Acheilognathus rhombea (known as the kanehira bitterling in Japan) were held under a constant short photoperiod (10 hr light-14 hr dark) at 25 degrees during their natural breeding season, the females spawned regularly at intervals of about 5 days. During each 5-day period, the oocytes passed through three distinct physiological stages: vitellogenesis (3 days), maturation (1 day), and spawning (1 day). During the maturational stage, germinal vesicle breakdown (GVBD) was first observed at 18 hr and was complete by 21 hr. Ovulation occurred at 24 hr. Steroid measurements made on plasmas collected from fish throughout their reproductive cycle showed that estradiol-17 beta levels were about 12 ng/ml at the beginning of the vitellogenic stage and about 5 ng/ml during the other stages. Testosterone levels were about 2 ng/ml during the vitellogenic stage, but fell to about 0.5 ng/ml during maturation and spawning. Progesterone levels were very low throughout the cycle and showed little variation. Both 17 alpha-hydroxyprogesterone and 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one levels were both very low (0.5 ng/ml) up until 12 hr on Day 4 (maturation), at which time they increased rapidly. The levels reached peaks of 4 and 7 ng/ml, respectively, at 18 hr and reached basal levels again at 8 hr the following day. GtH-like glycoprotein levels also began to increase at 12 hr on Day 4, but peaked later, at the time of ovulation (24 hr).

These studies were designed to investigate a possible effect of the monokine interleukin-1 alpha (Il-1 alpha) on gonadotropins and/or sex steroid secretion. Three putative sites of action were considered: the central nervous system, the pituitary, and the gonads. A central nervous system-mediated mechanism was tested by injecting Il-1 alpha into the lateral ventricle of the brain of castrated rats; this treatment caused a dose-related inhibition of LH secretion, with a minimum effective dose below 0.1 microgram (6.6 pmol) and a maximum effect at 1 microgram (66 pmol). The plateau response was observed 120 min after injection. The possibility that Il-1 alpha might alter pituitary sensitivity was studied by administering 200 ng GnRH, iv, into gonadectomized control rats or rats pretreated with 1 micrograms Il-1 alpha intracerebroventricularly. GnRH induced a comparable increase in the plasma LH levels of both groups of animals. Finally, hypophysectomized immature (24-day-old) female rats were used to determine if we could confirm in vivo that interleukin-1 alpha can act directly at the level of the ovary to interfere with steroidogenesis. In these animals, the sc injection of 20 IU PMSG produced a marked (P less than 0.01) increase in plasma estradiol levels, while the sequential injection of 20 IU PMSG and 1 microgram hCG significantly (P less than 0.01) stimulated progesterone release. The ip administration of 1 microgram Il-1 alpha every 12 h to gonadotropin-treated rats resulted in a significant inhibition of both estradiol and progesterone secretion. The results support possible roles for Il-1 alpha at the levels of the brain and the gonads, but not the pituitary, to inhibit reproductive functions.

The androgen-insensitivity syndrome (AIS) and Rokitansky syndrome (RS) are clinically similar except for H-Y antigen, chromosomal sex, gonadal sex, and the cyclicity of sex hormonal functioning. Nine AIS women and nine RS women could not be distinguished systematically on any of the following variables: romantic and genitoerotic imagery/ideation; sensory channels of erotic arousal; gender orientation; satisfaction with feminine status; self-rating of sexual frequency and interest; masturbation experience; orgasm experience; attitude toward marriage; and attitude toward infant and child care. These findings indicate that neither H-Y antigen status, chromosomal sex, nor hormonal cyclicity directly determines the differentiation of gender-identity/role (G-I/R) as male, female, or ambiguous. By implication, these findings are relevant to heterosexual/homosexual theory.