The Site of Inhibitory Action of a Natural (Corticosterone) and Synthetic Steroid (Dexamethasone) in the Hypothalamus-Pituitary-Adrenal Axis

Abstract

Only a few reports have appeared which have attempted to determine whether the naturally occurring steroid, corticosterone, has the same site of action in the hypothalamus-pituitary-adrenal axis as the synthetic steroid, dexamethasone. The present studies help to define the site of inhibition of both corticosterone and dexamethasone on the hypothalamus-pituitary-adrenal axis. Infusion of 20 or 202 µg corticosterone over 6 h significantly reduced hypothalamic CRF (corticotropin-releasing factor) content, whereas it did not reduce plasma ACTH levels in normal rats. This finding indicates the possibility that the infusion of corticosterone may decrease the hypothalamic CRF content by reducing CRF production or enhancing intracel-lular and/or extracellular CRF degradation. On the other hand, infusion of 20 µg dexamethasone for 6 h to normal rats significantly decreased plasma ACTH levels, but did not alter the hypothalamic CRF content. This finding indicates that dexamethasone may inhibit the release or/and production of ACTH in the anterior pituitary. In addition, relatively large doses of corticosterone (504 µg/rat) and dexamethasone (202 µg/rat) may suppress CRF content and ACTH release at the level of both the hypothalamus and anterior pituitary.