NEONATAL SEX-HORMONES HAVE ORGANIZATIONAL EFFECTS ON THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF MALE RATS

Sex hormones have activational effects on the hypothalamic-pituitary-a drenal (HPA) axis in adulthood: For example, corticosterone release is influenced by gonadal status. These experiments investigated whether sex hormones have organizational effects on the HPA axis of male rats: Do sex hormones have relatively permanent effects on its development? In adults, both neonatal (neoGDX) and adult gonadectomy (adult GDX) r esulted in elevated corticosterone (CORT) levels in response to stress compared to intact rats. Five days of testosterone propionate (TP) re placement was not as effective at attenuating CORT levels in neoGDX ra ts as in adult GDX rats. Neonatal GDX elevated corticosterone binding globulin (CBG) levels, whereas adult GDX was without effect. Ln Experi ment 2 the effects of neonatal gonadectomy and neonatal treatment with either TP, estradiol benzoate (EB), or oil vehicle was examined. Desp ite 14 days of hormone replacement, neoGDX showed elevated CORT levels in response to stress compared to all other groups. A single neonatal dose of TP or EB in neoGDX rats eliminated the increased responsivene ss. Neonatal TP and EB were without effect in sham-operated rats. Plas ma CBG levels were elevated in neoGDX groups regardless of neonatal ho rmone treatment. Corticosteroid receptor binding levels were examined in various brain areas and the pituitary in two groups most different in their androgen experience: NeoGDX and shams that did not receive tr eatments as adults. NeoGDX had lower levels of glucocorticoid receptor , and higher levels of mineralocorticoid receptor binding in the pitui tary. No other receptor differences were found. These experiments sugg est that neonatal sex hormones influence the sensitivity of the HPA ax is to sex hormones in adulthood and, thus, that they have organization al effects in addition to activational effects on HPA function. (C) 19 98 Elsevier Science B.V.