Prepubertal Increase Research Articles

Human-like adrenal development in wild chimpanzees: A longitudinal study of urinary dehydroepiandrosterone-sulfate and cortisol.

The development of theadrenalcortex varies considerably across primates, being most conspicuous in humans, where a functional zona reticularis-the site of dehydroepiandrosterone-sulfate (DHEA/S) production-does not develop until middle childhood (5-8 years). Prior reports suggest that a human-like adrenarche, associated with a sharp prepubertal increase in DHEA/S, may only occur in the genus Pan. However, the timing and variability in adrenarche in chimpanzees remain poorly described, owing to the lack of longitudinal data, or data from wild populations. Here, we use urine samples from East African chimpanzees (Pan troglodytes schweinfurthii) collected over 20 years at Kanyawara in Kibale National Park, Uganda, to trace the developmental trajectories of DHEAS (n = 1,385 samples, 53 individuals) and cortisol (n = 12,726 samples, 68 individuals). We used generalized additive models (GAM) to investigate the relationship between age, sex, and hormone levels. Adrenarche began earlier in chimpanzees (~2-3 years) compared with what has been reported in humans (6-8 years) and, unlike humans, male and female chimpanzees did not differ significantly in the timing of adrenarche nor in DHEAS concentrations overall. Similar to what has been reported in humans, cortisol production decreased through early life, reaching a nadir around puberty (8-11 years), and a sex difference emerged with males exhibiting higher urinary cortisol levels compared with females by early adulthood (15-16 years). Our study establishes that wild chimpanzees exhibit a human-like pattern of cortisol production during development and corroborates prior reports from captive chimpanzees of a human-like adrenarche, accompanied by significant developmental increases in DHEAS. While the role of these developmental hormone shifts are as yet unclear, they have been implicated in stages of rapid behavioral development once thought unique to humans, especially in regard to explaining the divergence of female and male social behavior before pubertal increases in gonadal hormones.

Maternal exposure to di-n-butyl phthalate induces alterations of c-Myc gene, some apoptotic and growth related genes in pups' testes.

The aim of this study was to investigate the effects of maternal exposure to di-( n-butyl) phthalate (DBP) on testicular development and function in pre-pubertal and post-pubertal male rat offspring. Fourteen pregnant female rats were equally divided into two groups: a control group and a DBP-treated group. During gestation day (GD) 12 to postnatal day (PND) 14, the control group was administered 1 ml/day corn oil, and the DBP-treated group was administered DBP 500 mg/kg/day by oral gavage. On PND 25 (pre-puberty) and PND 60 (post-puberty), blood for serum and the testes were collected from five male offspring of each group. To determine the relationship between the methylation state of the c-Myc promoter and the expression of the c-Myc gene, some apoptotic-related genes, such as p53 and Bax, the anti-apoptotic Bcl-2 gene, and some growth arrest-related genes, such as BRD7 and GAS1, were examined. Compared with the control ( p < 0.05), at pre-puberty, DBP induces c-Myc hyper-methylation with significant downregulation for c-Myc, p53, Bax genes, and significant upregulation for Bcl-2, BRD7, and GAS1, while at post puberty, the methylation state and expression of c-Myc and apoptosis-related genes returned to control levels in the same sequence with the fold change in the expression of BRD7 and GAS1 genes. These findings suggest that DBP induced a transient pre-pubertal increase in c-Myc promoter methylation that may be associated with disruption of both apoptotic and growth mechanisms in the testes.

Developmental effects of androgens in the human brain.

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions.

MITOCHONDRIAL DYSFUNCTION PLAYS A ROLE IN IMPAIRED NEURONAL DIFFERENTIATION IN SCHIZOPHRENIA

Schizophrenia (SZ) is conceptualized as a neurodevelopmental disorder, involving dysfunction of dopaminergic and glutamatergic systems as well as of mitochondria. Among the major obstacles in studying pathological processes in SZ are the inaccessibility of the brain and inability to study brain processes prior to the onset of this disorder. Animal models of the disease can shed light on possible developmental aberration in the disease. An additional attractive experimental tool to study neurodevelopmental impairments together with mitochondrial dysfunction in SZ, is differentiation of induced pluripotent stem cells (iPSC) into neurons.iPSC from SZ patients and healthy controls were reprogrammed from hair follicle keratinocytes and differentiated into dopaminergic and glutamatergic neurons. Mitochondria were assessed by analyzing mitochondrial membrane potential, network dynamics and apoptosis markers. The effect of transferring isolated active normal mitochondria (IAN-MIT) into SZ- iPSCs was studied. Furthermore, mitochondrial complex I subunits expression was followed in brains of neonatal ventral hippocampal (nVH) damage rat model of SZ.SZ-derived dopaminergic cells showed severely impaired ability to differentiate, whereas glutamatergic cells were unable to maturate. Mitochondrial complex I driven respiration was impaired in SZ-derived keratinocytes and iPSC along with perturbations in mitochondrial membrane potential and in mitochondrial network in neurons. However, amending mitochondrial function by IAN-MIT transfer improved differentiation of SZ-iPSC derived glutamatergic neurons. In prefrontal cortex, but not the cingulate cortex, of nVH damage rat model of SZ we observed a significant prepubertal increase and postpubertal decrease in mitochondrial complex I subunits. No such change was observed in neonatal exposure to hypoxia rat model.Our study shows perturbations in neural differentiation and mitochondrial function, which are interconnected and of relevance to early neurodevelopmental processes in SZ.

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain.

BackgroundResponsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.MethodsA multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6–10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH67) given once (GH67x1; n = 30) or divided into two daily injection (GH33x2; n = 36), or to remain on a single 33 μg/kg/day dose (GH33x1; n = 38). The outcome measures were change and obtained mean on-treatment IGF-ISDS, IGFBP3SDS and IGF-I/IGFBP3 ratioSDS during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS.ResultsMean prepubertal increases 1 year after GH start were: 2.1 IGF-ISDS, 0.6 IGFBP3SDS and 1.5 IGF-I/IGFBP3ratioSDS. A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in heightSDS. During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-ISDS was higher in GH67 vs GH33 (p = 0.031). First year pubertal ∆IGF-ISDS was significantly higher in the GH67vs GH33 group (0.5 vs −0.1, respectively, p = 0.007), as well as ∆IGF-ISDS to the pubertal mean level (0.2 vs −0.2, p = 0.028). In multivariate analyses, the prepubertal increase in ‘∆IGF-ISDS from GH start’ and the ‘GH dose-dependent pubertal ∆IGF-ISDS’ were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in heightSDS.Trial registrationTRN 88–177, not applicable 1988.ConclusionThe dose-dependent change in IGFs was related to a dose-dependent pubertal gain in heightSDS. The attempt to mimic normal physiology by giving a higher GH dose during puberty was associated with both an increase in IGF-I and a dose-dependent gain in heightSDS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0080-8) contains supplementary material, which is available to authorized users.

Interactive Effects of Dehydroepiandrosterone and Testosterone on Cortical Thickness during Early Brain Development

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

Sex-specific postnatal development of negative oestrogen feedback in rats.

Experiments were performed in immature and adult male and female rats to study the postnatal development of the negative oestrogen feedback in males and to investigate the mechanisms underlying this development. The following results were obtained: 1. Immature male and neonatally androgenized female rats were less responsive to the LH-inhibiting effect of oestradiol benzoate (OB) than untreated females. In contrast, long-term castrated adult males and females with the androgen-induced persistent oestrus syndrome were distinctively more sensitive than cyclic females to the negative feedback action of oestrogen. 2. The low oestrogen sensitivity in prepubertal males is probably caused by the testicular androgen secretion during the perinatal critical differentiation phase, because after neonatal castration, the LH response to OB injected at 21 days of age did not differ between both sexes. 3. As opposed to the peripubertal desensitization to the negative feedback action of testosterone, the sensitivity to the inhibitory effect of oestrogen on LH secretion did not decrease in males at the time of puberty. 4. Whereas former studies have shown that implantation of OB in the medial preoptic area results in significant reduction of the oestrogen sensitivity in female rats, medial preoptic implants containing oestradiol, testosterone or 5 alpha-dihydrotestosterone did not diminish the LH-suppressing effect of s.c. injected OB in males. The results suggest that 1. a marked sex difference exists in the postnatal development of the negative oestrogen feedback in rats. 2. Higher oestrogen sensitivity in adult male as compared to adult female rats may depend, at least partly, on prepubertal and cyclic desensitization of the negative oestrogen feedback in females and more or less constant sensitivity in males from infancy to adulthood. 3. In males the oestrogen sensitivity seems to be settled for long by the testicular androgen secretion during the perinatal critical differentiation phase. 4. The prepubertal increase of gonadotrophin secretion necessary for the induction of male puberty may mainly be caused by diminution of the gonadotrophin-inhibiting effect of androgens and by the decline of testicular release of inhibin. 5. The oestrogen-induced desensitization of the negative oestrogen feedback mediated by the medial preoptic area is probably a sex-specific mechanism that is only operative in female rats.

Mitochondrial Complex I Subunits are Altered in Rats with Neonatal Ventral Hippocampal Damage but not in Rats Exposed to Oxygen Restriction at Neonatal Age

Several independent lines of evidence suggest mitochondrial dysfunction in schizophrenia in brain and periphery, including mitochondrial hypoplasia, dysfunction of the oxidative phosphorylation system, and altered mitochondrial-related gene expression. In an attempt to decipher whether mitochondrial complex I abnormality in schizophrenia is a core pathophysiological process or is attributable to medication, we studied two animal models of schizophrenia related to the neurodevelopmental hypothesis of this disorder. Protein levels of complex I subunits, 24, 51, and 75 kDa, were assessed in neonatal ventral hippocampal lesion rat model and in rats exposed to hypoxia at a neonatal age. In the prefrontal cortex, a major anatomical substrate of schizophrenia, neonatal ventral hippocampal lesion induced a significant prepubertal increase and postpubertal decrease in all three subunits of complex I as compared to sham-treated rats, while no change was observed in the cingulate cortex. Neonatal exposure to hypoxia did not affect protein levels of any of the three subunits in the prefrontal cortex. An age-dependent increase in the expression of complex I subunits was observed, which was distorted in the prefrontal cortex by the neonatal ventral hippocampal lesion. Complex I alterations in schizophrenia-related neurodevelopmental rat models appear to be brain region and animal model dependent. The results of this study support previous findings suggesting abnormal complex I expression as a pathological characteristic of schizophrenia rather than an effect of medication.

Sex differences in the effect of prepubertal GALP infusion on growth, metabolism and LH secretion

The hypothalamic neuropeptide, galanin-like peptide (GALP), is known to have an effect on energy expenditure and reproduction in adult male rats, but little work has been done on prepubertal rats. We hypothesized that hypothalamic GALP is involved in physiological changes associated with the onset of puberty. To test this hypothesis, we first determined the postnatal ontogeny of GALP gene expression via in situ hybridization of developing male and female rat pups through adulthood. GALP gene expression was not observed in either male or female rat pups until after postnatal day (PND) 10 and did not reach adult-like levels until after weaning (PND25). To determine if exogenous GALP could induce the onset of puberty, PND25 male and female rats were implanted with lateral ventricular cannulas connected to an osmotic minipump that delivered either GALP or vehicle. GALP infusion significantly ( p < 0.05) increased body weight, food intake, and metabolic rate in male but not female rats compared to control infusion. After 2 weeks, GALP infusion had no significant effect on the onset of puberty, percent body fat, nor plasma levels of insulin, FSH or gonadal steroids in either sex; however, GALP did significantly ( p < 0.05) increase plasma levels of LH and leptin in male but not female rats and increased plasma growth hormone (GH) in both sexes. Our observations further demonstrate a sex difference in GALP responsiveness in prepubertal rats. These data suggest that GALP may be involved with the prepubertal increase in circulating leptin, LH, and GH resulting in an increase in metabolic rate and lean growth associated with puberty.

Arachidonic Acid Content in Adipose Tissue Is Associated With Insulin Resistance in Healthy Children

The fatty acid composition of membrane structural lipids, which is partly dependent on dietary intake, is associated with insulin action. To examine the association between fatty acid composition of adipose tissue and skeletal muscle phospholipids with insulin resistance markers in a healthy pediatric population. Using a cross-sectional design, we studied 83 healthy children divided into 3 groups, ages 2 to 5, 6 to 10 and more than 10 years. Fatty acid composition of adipose tissue triacylglycerols and skeletal muscle phospholipids, plasma lipid profile and fasting plasma levels of glucose and insulin were measured. There was a linear increase of insulinemia, glycemia and homeostasis adipose tissue model assessment (HOMA) index throughout the pediatric age range. Linoleic acid proportion in skeletal muscle and arachidonic acid proportion in adipose tissue also increased significantly with age. An age-independent positive correlation between insulinemia or HOMA index and arachidonic acid content in adipose tissue triacylglycerols (r = 0.47, P < 0.001) was found. An age-dependent negative correlation was present between insulinemia or HOMA index and oleic acid content in skeletal muscle phospholipids (r = -0.30, P = 0.03 and r = -0.28, P < 0.04, respectively). Trans fatty acids content did not correlate with any marker of insulin resistance. Healthy children present a prepubertal increase of insulin resistance, which is significantly correlated with arachidonic acid content in adipose tissue.

Gonadal defects and hormonal alterations in transgenic mice expressing a single chain human chorionic gonadotropin–lutropin receptor complex

To study the effects of premature and chronic ligand-mediated luteinizing hormone receptor (LHR) activation on reproductive development, we have generated transgenic mice expressing a genetically engineered, constitutively active yoked hormone-receptor complex (YHR), in which a fusion protein of human chorionic gonadotropin (hCG) is covalently linked to the N-terminus of rat LHR. YHR-expressing mice (YHR(+)) were analyzed at pre- and post-pubertal ages. Relative to wild type (WT) controls, male mice exhibited prepubertal increases in testosterone levels and seminal vesicle weights, and decreases in serum FSH, serum LH, testes weight, and the size of the seminiferous tubules. In adult male YHR(+) mice, testosterone and LH levels are not significantly different from WT controls. However, FSH levels and testes weights remain decreased. Female YHR(+) mice undergo precocious puberty with early vaginal opening, accelerated uterine development, enhanced follicular development, including the presence of corpora lutea, and an increase in serum progesterone. At 12 weeks of age, the ovary exhibits a relative increase in the amount of interstitial tissue, comprised of cells that are hypertrophic and luteinized, as well as follicles that are degenerating. Additionally, hemorrhagic cysts develop in approximately 25% of the transgenic mice. These degenerative changes are consistent with an aging ovary suggesting that CG-induced LHR activation in female mice leads to precocious sexual development and ovarian lesions. Taken together, these data indicate that the single chain YHR is functional in vivo and demonstrate that YHR(+) mice provide a novel system to further understand the reproductive consequences of aberrant LHR activation.

Prepubertal increases in the levels of two salmon gonadotropin-releasing hormone mRNAs in the ventral telencephalon and preoptic area of masu salmon

Ontogenic changes in the expression levels of two salmon gonadotropin-releasing hormone genes (sGnRH-I and -II) were examined in the forebrain region including the ventral telencephalon and preoptic area of masu salmon by competitive reverse transcription-polymerase chain reaction (RT-PCR). Two genes showed similar expression patterns throughout the lifetime in both sexes, although the levels of sGnRH-II mRNA were about 20 times higher than those of sGnRH-I mRNA. In males, the levels of sGnRH mRNAs increased at the beginning of the second year and reached their maximum in the autumn. The levels decreased gradually until the autumn of the third year when fish sexually matured. In females, the levels reached their maximum in the first autumn and fluctuated considerably along with the seasons in the third year. These results suggest that, in the salmon brain, sGnRH genes are activated long before the sexual maturation under sexually different control mechanisms.

Effects of polychlorinated biphenyls on the expression of KAP3 gene involved in the ‘critical period’ of rat brain sexual differentiation

There is a critical developmental period during which brain sexual differentiation proceeds irreversibly under the influence of gonadal hormone. Recently, kinesin superfamily‐associated protein 3 (KAP3) gene expressed during the ‘critical period’ of rat brain differentiation was identified by us (Choi and Lee, 1999). KAP3 functions as a microtubule‐based motor that transports membranous organelles anterogradely in cells, including neurons (Yamazaki et al., 1996). mRNA level of KAP3 gene markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited the prepubertal increase in KAP3 mRNA level (Choi and Lee, 1999). In the present study, we aimed to investigate the effects of polychlorinated biphenyls (PCBs), as endocrine disruptors (EDs) on the expression of KAP3 gene during the’ critical period’ of rat brain development. In our data, PCBs significantly decreased the expression of KAP3 gene in the fetal (day 17) and the neonatal (day 6 after birth in) male and female r...

Central administration of an antisense oligodeoxynucleotide against type I pituitary adenylate cyclase-activating polypeptide receptor suppresses synthetic activities of LHRH-LH axis during the pubertal process

In the present study, we determined the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP receptor type I (PAC 1) genes during juvenile development and the pubertal process. Female rats were assigned — based on uterine weights, the presence and abundance of uterine fluid, and their vaginal patency — to one of the following: anestrus (AE), early proestrus (EP), late proestrus (LP) or first estrus (E). The hypothalami from 22-, 24- and 26-day-old animals and from those in the peripubertal phases of AE, EP, LP and E were collected, and the content of PACAP and PAC 1 mRNA was assessed. These levels were found to decrease in EP and LP. To determine the effect of PACAP on prepubertal luteinizing hormone-releasing hormone (LHRH) and LH synthesis through PAC 1, a PAC 1 antisense oligodeoxynucleotide (ODN) was i.c.v.-administered, and mRNA levels of LHRH, LH β, and LHRH receptor (LHRH-R) were determined. Prepubertal increases in LHRH, LH β, and LHRH-R mRNA levels were markedly suppressed, and the onset of puberty was delayed by the i.c.v. injection of the antisense PAC 1 ODN. These data suggest that PACAP may play a role in the regulation of hypothalamic LHRH neurons, through which it regulates synthetic machinery of pituitary LH, during the pubertal process.

Effects of recombinant bovine somatotropin and dietary energy intake on growth, secretion of luteinizing hormone, follicular development, and onset of puberty in beef heifers.

The effects of dietary energy and recombinant bovine somatotropin (bST) on pattern of LH release, follicular development, and onset of puberty were studied in 40 Angus heifers. At 7 mo of age, heifers were assigned to a 2 x 2 factorial experiment; the main effects were dietary energy (high [HDE]: 14.15 Mcal of ME/d or moderate [MDE]: 10.84 Mcal of ME/d) and somatotropin (bST; 350 mg every 2 wk or vehicle). Beginning at 9 mo of age, heifers were observed twice daily for estrous activity. From 10.5 to 12 mo of age, five heifers from each treatment group were selected for weekly ultrasound examination of ovarian structures and biweekly sequential blood sampling to determine concentrations of LH. Somatotropin treatment altered intermediary metabolism in a manner consistent with enhanced accretion of lean tissue and decreased deposition of fat. The HDE heifers were younger (P < .001) at puberty than the MDE heifers, but BW at puberty was not different among treatment groups. Age and body weight at puberty were not affected by bST. Frequency of LH pulses increased within the 10.5 to 12 mo of age sampling window in HDE-treated heifers but not in MDE heifers (dietary energy x month of age; P < .02). Secretion of LH was unaffected by bST. Ovaries of bST-treated heifers tended (P < .09) to have fewer follicles > 5 mm in diameter than those of vehicle-treated heifers. We conclude that chronic treatment with bST did not alter age at puberty or pattern of LH release in heifers and that even modest differences in energy intake influence the timing of the prepubertal increase in pulsatile LH release.

Sexual maturation and seasonal changes in plasma levels of sex steroids and fecundity of wild Norway rats selected for reduced aggressiveness toward humans

Parameters of sexual maturation and reproductive function were compared in two groups of Norway rats, one selected for reduced aggressiveness towards man and the other for aggressiveness. It was found that selection for reduced aggressiveness produced an acceleration of sexual maturation as judged by earlier vaginal opening in the female and presence of mature spermatozoa in the testes of the male as well by earlier prepubertal increase in plasma testosterone in the male. In domesticated adults, seasonal variations in the parameters of the reproductive function narrowed; they showed neither the winter decrease in sexual activity nor the marked fall in plasma testosterone and estradiol exhibited by their aggressive counterparts.

Prepubertal increases in gonadotropin-releasing hormone mRNA, gonadotropin-releasing hormone precursor, and subsequent maturation of precursor processing in male rats.

Changes in gonadotropins and gonadal steroids during sexual maturation in rats and humans are well documented but little is known about hypothalamic gonadotropin-releasing hormone (GnRH) gene expression in relation to these events. This study measured hypothalamic proGnRH mRNA, GnRH precursor, and fully processed GnRH from postnatal day 8 until day 62 in male rats. GnRH precursor increased on day 22, reached a peak on day 24, declined on day 25 and returned to infantile levels by day 28. A secondary rise in precursor occurred at about day 40 when testosterone levels increased. GnRH mRNA increased on day 22 and remained elevated over the study period to day 26. GnRH increased on day 24 and remained at this level until a secondary rise occurred coincident with the testosterone rise at about day 40. The ratio of GnRH precursor to GnRH was high until day 24 and was low from day 26 onwards, reflecting a maturation of the processing enzyme system between these 2 d. Thus, an abrupt increase in GnRH gene transcription (mRNA) occurs early in juvenile male rats (day 22), well before the onset of puberty. An increase in GnRH precursor accompanies these early changes and this is followed by the maturation of processing as evidenced by the rapid decline of precursor and increase in GnRH from day 24 onward.

Effects of nutrition and season on the onset of puberty in the beef heifer.

Age at puberty is a major determinant of lifetime reproductive efficiency of beef cows. Research conducted during the past 20 yr has documented the major endocrine events leading to first ovulation in heifers. The critical event seems to be a prepubertal increase in pulsatile LH secretion. Environment influences timing of puberty onset in beef heifers. Nutrition and season are two of the better-defined variables that have been studied. Age at puberty is related inversely to plane of nutrition. The effect of nutrition on sexual maturation involves effects on timing of the prepubertal increase in LH secretion and seems to involve the LH pulse generating system located in the hypothalamus. The precise mechanism by which nutrition influences pulsatile LH secretion has not been elucidated, but signals reflecting metabolic status seem to be involved. Seasonal conditions of the early (birth to 6 mo of age) and late (6 to 12 mo of age) postnatal periods also influence timing of puberty onset in the heifer. Autumn-born heifers attain puberty at younger ages than do spring-born heifers, and exposure to spring-summer temperatures and photoperiods during the second 6 mo of life reduces age at puberty regardless of season of birth. Photoperiod may be the major seasonal cue that influences puberty onset in cattle. Limited evidence suggests that melatonin, a pineal hormone, is involved with transducing photic stimuli into neuroendocrine signals that influence LH secretion. If the physiological mechanisms mediating the effects of nutrition and season on timing of puberty onset are determined, then management strategies for reducing age at puberty can be enhanced.

Changes in the behaviour and androgen levels during pubertal development of the buffalo bull

Sexual behaviour and peripheral testosterone concentrations were studied longitudinally in a group of ten buffalo bulls of Nili-Ravi breed raised from birth under similar feeding and management conditions. Changes in sexual behaviour of these animals in response to a teaser bull were observed at weekly intervals from 15 months of age to attainment of puberty (mean age at puberty, 23.6 ± 0.9 months). Sexual behaviour of individual bulls was scored by a procedure based on an assessment of behavioural events and expressed as a percentage of the maximal points. These events ranged from reaction of the bull during approach towards the teaser to intromission and ejaculation in an artificial vagina. Serum testosterone was determined by radioimmunoassay in blood samples obtained at monthly intervals, from each bull. Analysis of behavioural data indicated a significant increase in sexual behaviour score (from 5 ± 2% to 40 ± 7%) 4–5 months prior to the attainment of puberty. Following a transitory decline, the sexual behaviour score reached a maximum (69 ± 5%) during the month in which first ejaculation with motile sperm was achieved. Behavioural profiles of individual bulls indicate that the period of prepubertal increase in sexual activity corresponded to the physiological puberty rather than to the chronological age of the bulls. The prepubertal as well as pubertal increase in sexual behaviour score was invariably preceded by a significant ( P < 0.05) elevation of serum testosterone concentrations. The data suggests that the prepubertal increase in sexual activity in the buffalo bull may serve as a criterion of onset of puberty and may be helpful in the selection of sires at a stage prior to sexual maturation.