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Influence of testosterone on precocious sexual development in immature rainbow trout.

The influence of testosterone on plasma and pituitary levels of gonadotrophin (GTH) as well as on gonadal development was studied in immature rainbow trout. Among the animals receiving a testosterone-cocoa butter implant (200 micrograms) at the age of 5 months, gonadal puberty occurred 8 months later in half of the males (opposite to the controls which remained immature) and the beginning of oocyte maturation was observed in only one female. These animals were characterized by a higher pituitary GTH level. Owing to the multivariate statistical analyses made, it was possible to provide evidence for the presence of two populations with different reactions to the same steroid treatment. They also confirmed the existence of a positive testosterone feedback, in the male, leading to a precocious gonadal development. The pituitary GTH load obtained with 200 micrograms of testosterone seemed to be related to the age of first maturation. The secretion of an appropriate level of GTH resulting in the stimulation of gametogenesis required the availability of a relatively large pituitary GTH level and seemed to be possible because the animals were already in the pubertal period. The fact that the highest pituitary GTH level of the treated lot was found in the only female showing a beginning of sexual maturation suggests that testosterone may also act in females.

Animals↗

Sexual development in the immature male blue fox (Alopex lagopus), investigated by testicular histology, DNA flow cytometry and measurement of plasma FSH, LH, testosterone and soluble testicular Mn2+-dependent adenylate cyclase activity.

Testicular weight in young male blue foxes increased steadily from 12 weeks of age (0.4-0.7 g) to reach peak values at the time of the mating season in March-April (5.2-6.6 g), before declining rapidly during May to low values in August at 63 weeks of age (1.3-1.6 g). Primary spermatocytes were found in the spermatogenic epithelium at 20 weeks of age and by late December (29 weeks of age) elongated spermatids were seen. There was a good correlation between the seasonal variations in the presence of germ cell types assessed by quantitative analysis of testicular histology and the variations in numbers of haploid, diploid and tetraploid cells measured by DNA flow cytometry: no haploid cells were found before the end of November and peak numbers were observed in March. Plasma FSH concentrations were increased from December onwards (with the exception of April). There were no clearcut seasonal variations in plasma LH concentrations although values were consistently lower in April. Testosterone concentrations were low for most of the year but increased from the end of January to the middle of April. There was no detectable seasonal variation in LH release in response to LHRH injection, and no typical pattern in plasma FSH concentrations during the first 100 min after injection. Plasma testosterone concentrations after LHRH injection rose gradually during testicular development. There were large seasonal variations in soluble Mn2+-dependent adenylate cyclase activity in the testis, that paralleled the changes in testicular weight and haploid cell content. Values were low until December and reached a peak at the time of the mating season before falling to basal levels again by June. The results suggest that immature male blue foxes reach full testicular development (indistinguishable from that of older animals) by the first mating season after birth at, an age of about 40 weeks.

Adenylyl Cyclases↗

Involvement of nerve growth factor in female sexual development.

The ovary is innervated by noradrenergic and peptidergic fibers. Treatment of neonatal rats with antibodies to nerve growth factor (NGF Ab) resulted in failure of the sympathetic (noradrenergic and neuropeptide-Y) nerves to develop. Partial loss of sensory innervation, represented by calcitonin gene-related peptide fibers, was also observed. Follicular growth was stunted, and production of androgens and estradiol was reduced. The timing of first ovulation was delayed, estrous cyclicity was disrupted, and fertility was compromised. Plasma LH levels were elevated, and LH pulsatility was enhanced, suggesting primary ovarian failure. A normal appearance of tyrosine hydroxylase-, LHRH-, and neuropeptide-Y-immunoreactive neurons in the hypothalamus, as determined by immunocytochemistry, suggested that neonatal immunosympathectomy did not directly affect hypothalamic reproductive function. In vitro release of LHRH from median eminence nerve terminals in response to prostaglandin E2 was, however, reduced in NGF Ab-treated rats. Normalization of the response by prior in vivo exposure of the animals to physiological estradiol levels, suggested that the diminished LHRH output was due at least in part to estrogen deficiency. Although ovarian dysfunction induced by immunosympathectomy may be related to alterations in vascular tone, the striking loss of perifollicular noradrenergic innervation caused by NGF Ab suggests that the absence of the nonvascular norepinephrine stimulus to follicular steroidogenesis is a primary factor responsible for the alterations observed. The results indicate that development of the sympathetic innervation of the ovary is NGF dependent and that NGF, by supporting the differentiation and survival of the innervating neurons, contributes to the acquisition of mature ovarian function.

Animals↗

Overexpression of a human transforming growth factor-alpha (TGF alpha) transgene reveals a dual antagonistic role of TGF alpha in female sexual development.

The importance of transforming growth factor-alpha (TGF alpha) in female reproductive development was assessed using transgenic mice bearing a human TGF alpha complementary DNA under the control of a mouse metallothionein-1 promoter (MT1-hTGF alpha). Examination of the brain and ovaries 5 h after a single sc injection of zinc chloride, administered to activate the MT1-hTGF alpha transgene, revealed that prominent sites of human TGF alpha messenger RNA expression within these tissues were the hypothalamus and ovarian follicles, respectively. In vitro experiments showed that acute transgene activation increased hypothalamic release of LH-releasing hormone. In contrast, the ovarian steroidal response to gonadotropins, examined in vitro, was markedly attenuated. Chronic activation of transgene expression by daily administration of zinc chloride delayed the time of first estrus (an index of peripubertal estrogen secretion), but shortened the interval between first estrus and the onset of estrous cyclicity (an index of reproductive competence). Accumulation of small antral follicles, accompanied by thecal hypertrophy and enhanced androgen production, preceded the acquisition of ovulatory capacity. These changes were accompanied by reduced serum LH levels, suggesting that the relative inability of small antral follicles to develop further in TGF alpha-overexpressing mice is at least in part due to inappropriate gonadotropin support. Serum LH levels in these animals may be reduced by an augmented androgen negative feedback signal. Nontransgenic mouse ovaries, placed under the control of a transgenic hypothalamus by heterologous grafting, rapidly ovulated and initiated estrous cyclicity. In contrast, acquisition of reproductive capacity was severely delayed in nontransgenic mice bearing transgenic ovarian grafts. The results indicate that TGF alpha regulates female reproductive development through two opposing mechanisms: within the brain, it facilitates the neuroendocrine activation of the process; at the ovarian level, modulates the stimulatory effect of gonadotropin hormones on follicular growth and steroidogenesis.

Animals↗

Effects of experimental Schistocephalus solidus infections on growth, morphology and sexual development of female three-spined sticklebacks, Gasterosteus aculeatus.

The use of naturally infected hosts in studies attempting to identify parasite-induced changes in host biology is problematical because it does not eliminate the possibility that infection may be a consequence, rather than a cause, of host trait variation. In addition, uncontrolled concomitant infections may confound results. In this study we experimentally infected individual laboratory-bred female three-spined sticklebacks Gasterosteus aculeatus L. with the pseudophyllidean cestode Schistocephalus solidus [Müller], and compared the morphology and growth patterns of infected females with sham-exposed controls over a 16-week period. Fish were fed a ration of 8% body weight per day. Non-invasive image analysis techniques allowed the growth of individual plerocercoids to be tracked in vivo throughout the course of infection, and patterns of host and parasite growth were determined. Females that developed infections diverged morphometrically from unexposed control females and exposed-uninfected females at 6 weeks post-infection, with the width of the body at the pectoral fins giving the earliest indication of infection success. When including the plerocercoid, infected females gained weight more quickly than controls, but when plerocercoid weight was removed this trend was reversed. There was no effect of infection on the increase in fish length. Plerocercoids grew at different rates in individual hosts, and exhibited measurable sustained weight increases of up to 10% per day. Final estimates of plerocercoid weight from morphometric analysis prior to autopsy were accurate to within +/- 17% of actual plerocercoid weight. At autopsy, infected female sticklebacks had significantly lower perivisceral fat reserves but had developed significantly larger ovaries than controls. The results are discussed in relation to previous studies examining natural infections, and the value of utilizing experimental infections to examine ecological aspects of host-parasite interactions is discussed.

Animals↗

Gonadotrophin stimulation in children with abnormal sexual development.

Plasma levels of testosterone were measured by radioimmunoassay before and after 3 days' administration of human chorionic gonadotrophin (HCG) 2,000 IU/d in 34 prepubertal boys (6 normal, 3 with anorchia, 5 with micropenis, 8 with cryptorchidism, 6 with hypogonadotrophic hypogonadism and 6 with hypospadias). The increase in plasma testosterone value ranged from 2.4 nmol/l to 10.5 nmol/l in normal boys. There was negligible (P greater than 0.05) response in boys with anorchia compared with normal children. Subjects with micropenis showed subnormal response (P greater than 0.05). Children with cryptorchidism showed a normal increase in testosterone levels (P greater than 0.05), but in those with hypogonadotrophic hypogonadism and hypospadias the increase was variable (1.2 - 8.8 nmol/l) (P greater than 0.05). Although the HCG stimulation test is not diagnostic in the majority of the sexual disorders, it appears to be sensitive for diagnosing anorchia.

Adolescent↗

Zinc status and sexual development in adolescent girls.

Forty-eight black adolescent girls, aged 8 to 16, from the inner city of Baltimore were divided into five groups according to breast and pubic hair development. Blood and hair zinc concentrations as analyzed by atomic absorption spectrophotometry were within ranges reported by other investigators. Hair zinc levels significantly increased (p less than .05) from the second to the last stage of puberty and were significantly correlated (p less than .05) with erythrocyte zinc levels, height, and weight. Mean dietary intakes of calories and protein, as measured from a 24-hour recall, were adequate and increased with stage of breast and pubic hair development. Mean zinc intakes reported in the 24-hour recall averaged 66% of the RDA in the latter half of puberty. It appeared that zinc nutriture was generally adequate in this population, even though the dietary intake of zinc was below the recommended level.

Adolescent↗

Inhibin-B in the male rhesus monkey: impact of neonatal gonadotropin-releasing hormone antagonist treatment and sexual development.

We examined the effect of reversibly suppressing pituitary-testicular function during the neonatal period on developmental changes in inhibin-B and FSH secretion in male rhesus monkeys. Infants were treated with either vehicle, a GnRH antagonist (Ant) or the Ant and androgen (Ant/And) for the first 4 postnatal months, and the effects on serum inhibin-B and FSH were monitored during the neonatal and peripubertal periods. In neonates, Ant or Ant/And treatment lowered both serum FSH and inhibin-B levels. By 12 months of age, inhibin-B concentrations no longer differed across treatment groups. A major increase in inhibin-B occurred between 27-36 months of age (late prepubertal period) in all groups, but levels were lower at 33 and 36 months of age in Ant/And-treated animals than in controls. These differences most likely were related to fewer Ant/And-treated animals achieving sexual maturity during their fourth year of life. Regardless of treatment, inhibin-B levels were higher in those that were destined to become mature (in year 4) than in those that were not. During the late prepubertal period, serum inhibin-B was positively correlated with age and testicular volume, but not with serum LH or testosterone. After this period (39-52 months of age), inhibin-B no longer correlated with these parameters. FSH levels were near or below detection limits in most peripubertal animals, but FSH was detectable in fewer samples from control than treated animals. The data suggest that inhibin-B secretion in the neonate is driven by gonadotropin secretion, but during the juvenile hiatus in gonadotropin secretion, the monkey testis continues to produce substantial amounts of this hormone.

Androgens↗

Effects of cadium on growth, sexual development, and metabolism in female rats.

Female rats were exposed to cadmium by multiple intramuscular injections of 250 mug CaCl2 for 54 days. Activity and haircoat were affected, sores on the sites of injection and persistent diestrus were observed in the treated rats. Morphological examination of organs revealed a smaller weight and size in reproductive organs and pituitary, but enlargement of liver, spleen, and kidney. The ratic enzymatic demethylation activity.

Animals↗

Effects of LHRH antagonist administration to immature male rats on sexual development.

Gonadotropin secretion in immature male rats was inhibited by administration of a potent LHRH antagonist (LHRH-A): from 6 to 15 days of age (early onset/short-term treatment), from 6 to 48 days of age (early onset/long-term treatment) or from 22 to 31 days of age (late onset/short-term treatment). Balano-preputial separation was retarded by 9 or 13 days (short-term treatments) or by about 40 days (long-term treatment). Adult testicular weight was lowered and plasma FSH was increased after early, but not after late onset of LHRH-A treatment. Plasma LH and testosterone levels were not affected by any of the LHRH-A treatments. Fertility was diminished after early onset LHRH-A administration only. Adult precopulatory and copulatory behavior were severely affected after early onset of LHRH-A treatment. Intensity of precopulatory anogenital inspection was increased. The copulatory pattern was incomplete with absence of ejaculatory behavior during sexual behavior tests. Sexual behavior was not affected after late onset of LHRH-A treatment. Thus, administration of LHRH-A to immature male rats delays balano-preputial separation irrespective of the age of onset of LHRH-A treatment. In contrast, effects on adult FSH levels, testicular weight, fertility and sexual behavior depend on age and duration of LHRH-A administration.

Animals↗

Effect of selective removal of the adrenal medulla on female sexual development.

The ovary and adenohypophysis of the rat contain beta-adrenergic receptors and respond to beta-adrenergic stimulation with hormone release. To determine the importance of the adrenal medulla as a source of adrenergic influences regulating prepubertal ovarian and pituitary function, a technique was developed to remove most of the adrenal medulla without compromising adrenocortical function. Medullectomy (MED) of 24-day-old female rats depressed both spontaneous diurnal changes in plasma epinephrine (EPI), and the EPI and norepinephrine (NE) response to decapitation, without affecting corticosterone (B) levels. Vaginal opening and first ovulation were delayed in MED rats. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were normal in MED rats, but those of growth hormone (GH) and prolactin (Prl) were depressed. MED reduced the ovarian weight response to pregnant mare's serum gonadotropin (PMSG) and the ovarian steroidal response to human chorionic gonadotropin (hCG) in vitro, but it did not affect ovarian beta-adrenergic receptors. Cultured granulosa cells, harvested from juvenile ovaries and primed in vitro with FSH, responded to nanomolar concentrations of EPI with progesterone (P) secretion. EPI also augmented hCG- and FSH-induced P secretion. The EPI effect was reproduced by Zinterol, a beta 2-adrenergic agonist and was prevented by propranolol, a beta-adrenergic antagonist. Blockade of alpha-adrenergic receptors with phentolamine was ineffective. It is suggested that EPI of adrenomedullary origin supports female prepubertal development by a) stimulating ovarian P secretion, b) favoring Prl and GH release and c) amplifying the stimulatory effect of low gonadotropin levels on ovarian steroidogenesis. The effects of EPI on ovarian function appear to be mediated by beta-adrenergic receptors of the beta 2 type.

Adrenal Medulla↗

[Hormonal suppression and sexual development in children with central precocious puberty in the first treatment cycle 12 weeks after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg): a pilot study].

OBJECTIVE: To evaluate hormonal suppression and pubertal development in children with central precocious puberty (CPP) after injection of triptoreline 11.25 mg (Diphereline S. R. 11.25 mg; Ipsen) in the first treatment cycle of 12 weeks. DESIGN: Pilot study. SETTING: Paediatric department, University Hospital Motol-Prague. METHODS: Serum levels of FSHmax and LHmax and basal levels of estradiol/testosterone were monitored in GnRH test before, 4, 8 and 12 weeks after triptoreline 11.25 mg injection in 3 girls and 2 boys with CPP (age 3.9-10.6 years) previously treated by triptoreline 3 mg every 4 weeks. Uterine and ovarian volume, hormonal cytology (vaginal smear), breast development and testicular volume were evaluated before and 12 weeks after triptoreline 11.25 mg injection. RESULTS: 8 weeks after triptoreline 11.25 mg, FSHmax in girls increased (2.3 IU/l vs. 1.7 IU/l before injection; median) without any other change in 12th week. In boys after initial decrease LHmax 12 weeks after injection rose to 1.7 IU/l (identical as LHmax before injection). Estradiol and testosterone levels were in prepubertal range. Pubertal development in girls did not progress, and testicular volume decreased in both boys (treated for CPP 0.3 and 0.7 years). CONCLUSIONS: Triptoreline 11.25 mg injection in 12 weeks interval can be considered as effective, useful and safe for therapy of CPP. The long-term follow-up will be necessary.

Child↗

[Sexual development: development of secondary sex characteristics--Tanner stages 25 years later].

In a longitudinal study the british pediatrician J.M. Tanner evaluated the development of breasts (thelarche), of pubic hairs (pubarche) and age of menarche. In Hungary we did a similar evaluation in 680 girls in the years 1980 to 1986. Comparing these data in a cross-sectional study with similar data from Münster we named the results central-european study. The results are similar the Tanner ones exceptionally the duration of breast development, which was shorter than in the hitherto published longitudinal studies. Mean age of menarche in our study was 12.5 years compared with 13.5 years in the former ones. This is not a confirmation to acceleration of puberty, because in other countries age of menarche was stabile. Additionally, to thelarche, pubarche and menarche we collected data about axillarche.

Adolescent↗

Light-related melatonin changes in pituitary response to gonadotropin-releasing hormone during sexual development in the female rabbit.

Melatonin levels in the blood of female rabbits were determined from the time of weaning to adulthood in a longitudinal study. Blood samples were taken at 3 h after light onset and 1 h after dark onset and plasma was analysed for melatonin, LH and FSH by radioimmunoassay procedures. The animals were sacrificed on days 25, 32, 39, 51, 72, 91 and 120 days of life and pituitaries removed for in vitro incubation of slices to determine their response to GnRH. Circulating melatonin levels were significantly higher in the dark compared to the light phase and peaked on days 72 and 91 when gonadotropin levels were at a nadir. Melatonin levels on day 120 were lower than those on any other day examined. Basal secretion of LH and FSH by pituitary slices in vitro increased several-fold from day 25 of age to days 51-91 and then decreased by day 120. The pituitary gonadotropin responsiveness to GnRH in vitro was also different: while LH generally increased, FHS accumulation remained constant after GnRH stimulation. These data suggest that the female rabbit pituitary undergoes changes in sensitivity to GnRH during sexual maturation and that the pineal gland may play a role in this process.

Aging↗

Effects of cefonicid and other cephalosporin antibiotics on male sexual development in rats.

The purpose of this study was to determine whether cefonicid, a cephalosporin antibiotic with a modified N-methylthiotetrazole (MTT) side chain, caused testicular toxicity when subcutaneously administered to Sprague-Dawley male rats from days 6 to 36 postpartum at doses of 50 to 1,000 mg/kg per day. Moxalactam (a cephamycin antibiotic which will be referred to as a cephalosporin for convenience throughout), which contains the MTT side chain, was used as a positive control and was administered at 100 to 1,000 mg/kg per day, and cephalothin, which lacks an MTT side chain, was used as the negative control at 1,000 mg/kg per day. Moxalactam caused a significant reduction in testicular and seminal vesicle weights in 37-day-old animals, and histological examination revealed bilateral multifocal atrophy of the seminiferous tubules at all dose levels. Animals reared to reproductive maturity had significant deficits in fertility, and histological examination revealed multifocal or diffuse atrophy of the seminiferous tubules at all doses with a severity greater than that observed in the 37-day-old animals. The histological findings were confirmed by marked reductions in testicular sperm production rates and cauda epididymal sperm numbers. Cephalothin and cefonicid had no treatment-related adverse effects on the sexual maturation of prepubertal, juvenile, or adult males. The absence (in cephalothin) or modification (in cefonicid) of the MTT side chain was not associated with adverse reproductive effects. The relevance of these findings to humans in prenatal and prepubertal stages of life cannot be determined at this time.

Age Factors↗

Physical, hormonal and behavioural aspects of sexual development in the marmoset monkey, Callithrix jacchus.

Measurements of growth, plasma progesterone and testosterone levels, and copulatory behaviour were obtained from captive marmosets from birth until 600-800 days of age. Body weight and knee-to-heel length were similar for both sexes. Males exhibited a neonatal testosterone surge from 15-100 days and testosterone levels began to rise again, coincident with the growth of the testis, at about 250 days. The males were copulating by 400-500 days of age. Paired females were apparently ovulating and able to conceive from about 400 days. In peer groups, only the dominant female became pregnant, because subordinate females failed to ovulate.

Animals↗

Influence of a low plane of nutrition during sexual development on subsequent reproductive performance of small white breeder toms.

Diamond White and Wrolstad breeder toms were reared to 10 weeks of age on a common nutritional regimen. Both strains were subsequently given high and low planes of nutrition to 30 weeks. Low nutrient feeds were ca. 200 kcal of metabolizable energy (ME)/kg less than high nutrient feeds, which paralleled commercial practice. Energy-protein ratio and essential amino acid profiles between nutrient levels were similar. Both planes were phased down ca. 200 kcal ME/kg between the feeds from 10 to 14 weeks to 14 to 30 weeks. All birds subsequently received the same breeder ration. Diamond Whites were heavier than Wrolstads from 2 through 10 weeks of age. Feeding the low plane of nutrition reduced body weight of both strains at 14 weeks. Growth during the 14- to 30-week-period was such that birds given the low plane feeds recovered earlier losses, and Wrolstads became heavier than Diamond Whites. Although no differences in body weight occurred throughout the breeder period that could be attributed to earlier nutrition, the low plane feeds led to significant improvements in semen and sperm yield during the early and late stages. Wrolstads accrued more fat and benefited more from the low plane of nutrition than did Diamond Whites. Results inferred that reducing fat accretion early in sexual maturity improves subsequent reproductive capacity apart from an alteration in body weight.

Animals↗

[Methods for correcting retardation of sexual development in the irregular puberty syndrome in boys].

A total of 46 boys aged 11 to 13 with the abnormal puberty syndrome were examined. The authors assessed various methods of correction of delayed puberty by the time course of anthropometric and genitometric indices and blood testosterone, LH and FSH levels 1 year after the initiation of treatment, at the age of 14 to 16 and 17 to 19. The ejaculate composition of 12 adolescents over 17 was examined. In 3/4 of the adolescents the indices of physical development and pubescence, blood testosterone and gonadotropic hormone levels achieved physiological values by the age of 14-16, but in 1/4 of the patients delayed puberty with lowered FSH and testosterone levels and raised LH in the blood was noted. The normalization of puberty was noted at the age of 17 to 19 with normal spermatogenesis. The necessity and methods of therapeutic correction of delayed puberty in boys and adolescents with the abnormal puberty syndrome were discussed.

Adolescent↗