Neonatal ACTH and corticosterone alter hypothalamic monoamine innervation and reproductive parameters in the female...

Female Sprague-Dawley rat pups were injected SC with either ACTH(1-24) (0.5 mg/kg) or saline vehicle once daily from postnatal day 1 (day of birth) to day 7. Plasma corticosterone (CORT) levels were recorded via radioimmunoassay (RIA) on day 4 to measure adrenal response to these treatments. Hypothalamic 5-HT and DA fiber densities were assessed using high-affinity specific 3H-5-HT and 3H-DA uptake at days 7, 25, and at adulthood (80-90 days). Animals were checked daily for vaginal opening (starting on day 30) as a sign of sexual maturation and later tested for sexual behavior as virgins (60-70 days of age). Plasma estradiol and progesterone levels were measured via RIA. Plasma CORT levels were greatly increased among ACTH-treated animals during the treatment period. The 5-HT uptake was significantly increased in ACTH-treated animals at day 7 (p < 0.01) and at adulthood (p < 0.02) compared to controls. The DA uptake was significantly higher among ACTH-treated animals at day 7 (p < 0.01). The sexual maturation of ACTH-treated animals was delayed when compared to control animals (p < 0.01). The ACTH-treated animals displayed slight deficits in female sexual behavior compared to control animals (p < 0.05). No significant changes in plasma sex steroid levels were found. Based on this study, we suggest that monoamine innervation into the developing female hypothalamus is susceptible to early postnatal manipulation with ACTH and CORT, and that the resulting changes in these monoamine fiber densities may be responsible for the observed deficits in reproductive maturation and behavior.