Androstadienone odor thresholds in adolescents

A sex-related difference in olfactory sensitivity to androstenone has been reported to occur during adolescence. More males than females exhibited anosmia to androstenone, or an increase in androstenone threshold with age. The current study addressed the question whether similar, sexually dimorphic effects of aging over puberty can also be found for androstadienone. A total of 102 subjects participated (36 females, 66 males). Similar to previous investigations, subjects were divided into a group of 47 individuals with a mean age of 13.3 years, defined as pre/peri-pubertal, and a group of 55 subjects with a mean age of 17.1 years, defined as post-pubertal. All subjects underwent tests for verbal abilities, general olfactory function, and measurements of androstadienone thresholds. The study provided the following major results: (1) Male subjects exhibited higher androstadienone sensitivity in the pre/peri-pubertal group as compared to the post-pubertal group. This difference was not observed in female subjects. Correspondingly, a negative correlation between age and androstadienone sensitivity was found for male subjects, but not for female subjects. (2) In contrast to this sex-specific change of the androstadienone odor threshold, verbal skills and odor identification abilities increased with age in all subjects regardless of their sex. In conclusion, the present observations confirm previous research on sex-differentiated effects of aging during puberty on sensitivity towards odorous steroids. While the underlying causes are unknown, it may be hypothesized that the decreased sensitivity could result from the increased endogenous levels of androstadienone in male subjects. Future studies should include both steroid and non-steroid odorants to further explore these age-related changes.     

Chronic somatostatin treatment affects pituitary gonadotrophs, ovaries and onset of puberty in rats

The effects of chronic somatostatin (SRIH-14) treatment on the pituitary gonadotrophs (FSH and LH cells) and ovaries of female Wistar rats were examined. Females were given 20 microg/100 g b.w. twice per day from the immature (23rd day) till the adult period of life (71st day). The onset of puberty was determined by daily examination for vaginal opening. The peroxidase-antiperoxidase immunocytochemical procedure was used to study the gonadotrophs. Changes in the number per unit area (mm2), cell volume and volume densities of LH- and FSH-immunoreactive cells were evaluated by morphometry and stereology. Ovaries were analysed by simple point counting of follicles and corpora lutea (CL). Follicles were divided by size according to the classification of Gaytán and Osman. The mitotic indexes of granulosa and theca cells in the follicles were estimated at all stages of folliculogenesis. The number, volume and the volume density of FSH- and LH-immunoreactive cells decreased after chronic SRIH-14 treatment, particularly the latter. In the ovary, SRIH-14 treatment decreased the number of healthy follicles at all phases of folliculogenesis, lowered the mitotic indexes of granulosa and theca cells but increased the number of atretic follicles. Healthy CL were fewer in number, while regressive CL were increased. Vaginal opening occurred at a later age in treated females. It can be concluded that chronic SRIH-14 treatment markedly inhibited LH cells and to a lesser extent FSH cells. In the ovary SRIH-14 inhibited folliculogenesis, enhanced atretic processes and lowered proliferative activity of granulosa and theca cells. It also delayed puberty onset.     

Regulation of gonadotropin secretion and puberty onset by neuromedin U

Neuromedin U (NMU), an anorexigenic peptide, was originally isolated from porcine spinal cord in 1985. As NMU is abundant in the anterior pituitary gland, we investigated the effects of NMU on gonadotropin secretion. Both NMU and its receptors, NMUR1 and NMUR2, were expressed in the pituitary gland. NMU suppressed LH and FSH releases from rat anterior pituitary cells. Moreover, NMU-deficient mice exhibit an early onset of vaginal opening. The LHbeta/FSHbeta ratio, which is an index of puberty onset, is high in young NMU-deficient mice. These results indicate that NMU suppresses gonadotropin secretion and regulates the onset of puberty.     

缓释型促性腺激素释放激素与生长激素治疗儿童中枢性性早熟的疗效观察

目的用生长激素与促性腺激素释放激素类似物(Gonadotropin-releasing hormone analogues,GHA)联合治疗中枢性性早熟女性患儿对其最终成人身高的影响.方法生长激素(GH)与促性腺激素释放激素类似物(GHA)联合治疗4例中枢性性早熟女性患儿半年,对比治疗前后患儿的第二性征,骨龄发育,性激素及最终成人身高的变化.结果第二性征的发育停止,骨龄发育被控制,实际生活年龄与骨年龄的比值提高(平均0.79→0.84);血LH对促性腺激素释放激素的反应及血浆雌激素水平平均已降至青春期前,分别为(平均25.79±10.60mlu/ml→1.13±0.21mlu/ml)及(平均64.87±27.51pg/ml→3.03±1.87pg/ml);预测最终成人身高增加(平均149.60±4.31cm→156.75±3.84cm)差异具有显著性(P＜0.05).结论生长激素与GHA联合治疗中枢性性早熟患儿,不仅能抑制第二性征发育,而且能有效改善最终成人身高,无任何毒付作用.     

Lability of fat stores in peripubertal wild house mice

Summary Traditionally, the adaptive value of mammalian white fat stores is considered in relation to longterm needs such as providing protection against the vagaries of winter or signalling the reproductive system when energy reserves are sufficient to risk pregnancy. As shown here, the fat stores of young house mice could not serve such needs. Despite prolonged acclimation and excess nesting material, food deprivation at 10°C significantly lowered the fat stores of peripubertal female house mice in only 12 h, and would exhaust them in 30 h. Even close to thermoneutrality (24°C) the calculated time to exhaustion was only 70 h. The fat stores of a young house mouse are obviously too meager to offer any meaningful protection over a winter of several months duration, or even over a 5–6-week cycle of pregnancy and lactation. Furthermore, in a wild habitat where food availability and ambient temperature can vary rapidly and greatly, such fat stores would be too labile to effectively coordinate puberty with somatic development.     

Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls

Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4). Total breast volume, absolute fibro-glandular volume (FGV), and %FGV were evaluated at B4 using dual X-ray absorptiometry. The impact of AgeAccel (mean: 0; SD: 3.78) across puberty on the time to breast development (thelarche), menarche, and pubertal tempo (thelarche to menarche) was estimated using accelerated failure time models; generalized estimating equations were used to evaluate associations with breast density. A five-year increase in average adolescent AgeAccel was associated with a significant decrease in time to menarche [hazard ratio (HR): 1.37; 95% confidence interval (CI): 1.04, 1.80] adjusting for birth weight, maternal pre-pregnancy body mass index, maternal height, maternal education, B2 height, fat percentage, and cell composition. AgeAccel displayed a stronger inverse association with pubertal tempo (HR: 1.48; 95% CI: 1.10, 1.99). A five-year increase in AgeAccel was associated with 5% greater %FGV, adjusting for B4 percent body fat, and maternal traits (95% CI: 1.01, 1.10). Our study provides unique insight into the influence of AgeAccel on pubertal development in girls, which may have implications for adult health.     

Consequences of in ovo exposure to p,p'-DDE on reproductive development and function in Japanese quail

This study was conduced to assess the effects of a one time embryonic exposure to p,p'-DDE (dichlorodiphenyldichloroethylene; DDE) on the reproductive development and function in Japanese quail (Coturnix japonica). Embryos were exposed at day one of incubation to either 20 or 40 microg DDE or a sesame oil vehicle control (injection volume=20 microl). Onset of puberty, gonadal histopathology, sperm motility, cloacal gland size, and male copulatory behavior were assessed in adults. DDE accelerated onset of puberty in females and reduced male reproductive behaviors. Gonadal morphology and sperm motility appeared to be unaffected. Results from this study provide evidence that the neuroendocrine system may be more sensitive and less resilient to embryonic exposure to contaminants than traditional measures of reproductive success following contaminant exposure in adults. This study further supports the inclusion of behavioral assessments in toxicity tests.     

Gonadectomy negatively impacts social behavior of adolescent male primates

Social behavior changes dramatically during primate adolescence. However, the extent to which testosterone and other gonadal hormones are necessary for adolescent social behavioral development is unknown. In this study, we determined that gonadectomy significantly impairs social dominance in naturalistic settings and changes reactions to social stimuli in experimental settings. Rhesus macaques were castrated (n =  6) or sham operated (n = 6) at age 2.4 years, group-housed for 2 years, and ethograms were collected weekly. During adolescence the gonadally intact monkeys displayed a decrease in subordinate behaviors and an increase in dominant behaviors, which ultimately related to a rise in social status and rank in the dominance hierarchy. We measured monkey's reactions to emotional faces (fear, threat, neutral) of conspecifics of three ages (adult, peer, infant). Intact monkeys were faster to retrieve a treat in front of a threatening or infant face, while castrated monkeys did not show a differential response to different emotional faces or ages. No group difference in reaction to an innate fear-eliciting object (snake) was found. Approach and proximity responses to familiar vs unfamiliar conspecifics were tested, and intact monkeys spent more time proximal to a novel conspecific as compared to castrates who tended to spend more time with a familiar conspecific. No group differences in time spent with novel or familiar objects were found. Thus, gonadectomy resulted in the emergence of significantly different responses to social stimuli, but not non-social stimuli. Our work suggests that intact gonads, which are needed to produce adolescent increases in circulating testosterone, impact social behavior during adolescences in primates.     

Long-term alteration of anxiolytic effects of ovarian hormones in female mice by a peripubertal immune challenge

Recent reports indicate that exposure to some stressors, such as shipping or immune challenge with the bacterial endotoxin, lipopolysaccharide (LPS), during the peripubertal period reduces sexual receptivity in response to ovarian hormones in adulthood. We hypothesized that a peripubertal immune challenge would also disrupt the response of a non-reproductive behavior, anxiety-like behavior, to ovarian hormones in adulthood. Female C57Bl/6 mice were injected with LPS during the peripubertal period and tested for anxiety-like behavior in adulthood, following ovariectomy and ovarian hormone treatment. Treatment with estradiol followed by progesterone reduced anxiety-like behavior in control, but not LPS-treated females. We next determined if the disruptive effect of LPS on adult behavior were limited to the peripubertal period by treating mice with LPS either during this period or in adulthood. LPS treatment during the peripubertal period disrupted the anxiolytic effect of ovarian hormones, whereas treatment in adulthood did not. We further tested if this model of peripubertal immune challenge was applicable to an outbred strain of mice (CD-1). Similar to C57Bl/6 mice, LPS treatment during the peripubertal period, but not later, disrupted the anxiolytic effect of estradiol and progesterone. These data suggest that a peripubertal immune challenge disrupts the regulation of anxiety-like behavior by ovarian hormones in a manner that persists at least for weeks after the termination of the immune challenge.