Androgen-sensitive changes in regulation of restraint-induced adrenocorticotropin secretion between early and late puberty in male rats.

Regulation of ACTH secretion changes between early (40 d) and late (60 d) puberty in male rats. We tested whether this occurs because of activating effects of testosterone on the brain. We measured testosterone and ACTH responses to repeated restraint in adrenalectomized, corticosterone-replaced rats entering and leaving puberty with or without treatment with flutamide, a nonsteroidal androgen-receptor antagonist. Flutamide increased testosterone. ACTH responses were high and suppressed by flutamide at 40 d. At 60 d, ACTH responses were low and increased by flutamide. On d 4, basal arginine vasopressin (AVP) mRNA was increased by restraint, but not age, in the medial parvicellular paraventricular nucleus (mpPVN) and medial amygdala and increased with age in the bed nucleus of the stria terminalis. We counted numbers of AVP-immunoreactive (AVP-ir) and corticotropin-releasing factor (CRF)-ir neurons. In medial amygdala, there was no change in AVP+ cells. With restraint, CRF+ cells in the central nucleus decreased at 40 d and increased at 60 d. Flutamide did not affect the response at 40 d but blocked restraint-induced increases at 60 d. After restraint, the bed nucleus of the stria terminalis AVP-ir correlated negatively with mpPVN CRF-ir at 40 d and with mpPVN AVP-ir at 60 d. In PVN, there were no effects on CRF+ cells. However, AVP+ cells increased only with restraint plus flutamide at 40 d and tended to increase with restraint and decrease with restraint plus flutamide at 60 d. We conclude that during puberty testosterone induces marked changes in regulation of neuropeptides in pathways known to determine autonomic, neuroendocrine, and behavioral responses to chronic stress.