Persistent Effects of Prenatal, Neonatal, or Adult Treatment with Flutamide on the Hypothalamic–Pituitary–Adrenal Stress Response of Adult Male Rats

Abstract

To explore the role of androgens in early development on adult hypothalamic–pituitary–adrenal (HPA) function in males, we administered flutamide or vehicle injections: (1) to pregnant dams on embryonic days 15–20; (2) to neonatal pups on days 0–5; or (3) to adults on days 55–60. At approximately 70 days of age, trunk blood was collected to determine corticosterone levels (1) upon removal from the home cage, (2) immediately after 30 min of restraint stress, or (3) 60 min after return to home cage following the stressor. Flutamide treatment resulted in higher basal levels of testosterone and stress levels of corticosterone compared to vehicle treatment, and there was no interaction of treatment with age at time of treatment. This suggests that testosterone is less effective at inhibiting HPA function in flutamide-treated males. In addition, prenatally treated males had higher stress levels of corticosterone than neonatally and adult-treated males, regardless of the type of treatment. There were no differences in CBG levels among the groups. The results suggest that, in males, flutamide treatment has a long-lasting effect on HPA function. These results are consistent with our previous research on neonatally gonadectomized males and the hypothesis of organizational effects of sex hormones on HPA function.