Factors Regulating the Timing of Puberty Onset in Female Rhesus Monkeys (Macaca mulatta): Role of Prenatal Androgens, Social Rank, and Adolescent Body Weight1

Abstract

This study investigated whether prenatal androgen exposure, social rank, and body weight are factors regulating pubertal development in outdoor-housed female rhesus monkeys. Subjects' mothers received injections of testosterone enanthate (20 mg/ wk), flutamide (an androgen receptor blocker, 30 mg/kg twice daily), or vehicle during Gestational Days 35/40-70 (early) or Days 105/110-140 (late). Monitoring of pubertal development began around 28 mo of age during the fall breeding season, with frequent assessment of menstruation, circulating steroids, and weight. Menarche occurred 1.5 mo later in females treated late in gestation than in females treated early in gestation. This short menarche delay occurred in females treated with androgen, flutamide, or vehicle. No effect of prenatal manipulations on first ovulation were found. Social rank was related to first ovulation but not menarche, with low-ranked females less likely than high- or middle-ranked females to ovulate at 2.5 yr than at 3.5 yr of age. Females ovulating early, around 2.5 yr, had higher pubertal body weights and body mass indexes (BMI) than did females ovulating later, suggesting that better nutritional reserves or positive energy balance affect pubertal development. Thus, social rank and likely nutritional status influenced pubertal development in this study. Hormonal manipulations had no detectable effect; instead, handling late in gestation, which may have increased maternal adrenal activity, delayed menarche. This finding contrasts with earlier studies that showed that prenatal androgens delay menarche by 4-6 mo on average. This study supports late gestation as a period of increased sensitivity to environmental insult and demonstrates that multiple factors, including prenatal programming, modulate the specific timing of pubertal events.