Feedback Regulation of Adrenocorticotropin Secretion in “Basal” and “Stress” Conditions: Acute and Chronic Effects of Intrahypothalamic Corticoid Implantation

Abstract

To study hypothalamic involvement in the negative feedback regulation of ACTH secretion, the effects of intrahypothalamic implantation of various corticosteroids and ACTH on plasma corticosterone and adrenal weight were investigated in male rats. Plasma corticosterone responses to ether stress were blocked 5, 10 and 15 days following implantation of crystalline dexamethasone or cortisol acetate in the median eminence; pituitary and adrenal weights were also decreased. Corticosterone acetate implantation produced little or no inhibitory effect. Basal (resting) am levels of plasma corticosterone were reduced significantly by cortisol acetate implantation in 2 of 3 experiments. ACTH implants had no effect on the stress response. Seven days following hypothalamic implantation of cortisol acetate, adrenal sensitivity (response to exogenous ACTH) was reduced, but not sufficiently to account for the inhibition of the stress response. Furthermore, the response to electric shock was significantly inhibited 4 hr after cortisol acetate implantation, presumably before adrenal sensitivity could be reduced. Measurements of the responses to shock were performed 4, 12 and 24 hr following implantation of 30, 60, 120 or 240 μg cortisol acetate. Responses decreased as post-implantation period or dose increased. It appears that suppression of stress responses by corticoid implantation in the basal hypothalamus cannot be explained by decreased adrenal sensitivity. It occurs soon after intrahypothalamic administration of corticosteroid in doses well below those effective systemically. (Endocrinology82: 655, 1968)