The site of inhibitory action of a natural (corticosterone) and synthetic steroid (dexamethasone) in the hypothalamic-pituitary-adrenal axis.
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 microgram corticosterone over 6 h significantly reduced hypothalamic CRF (corticotropin-releasing factor) content, whereas it did not reduce plasma ACTH levels in normal rats. The finding indicates the possibility that the infusion of corticosterone may decrease the hypothalamic CRF content by reducing CRF production or enhancing intracellular and/or extracellular CRF degradation. On the other hand, infusion of 20 microgram 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 and/or production of ACTH in the anterior pituitary. In addition, relatively large doses of corticosterone (504 microgram/rat) and dexamethasone (202 microgram/rat) may suppress CRF content and ACTH release at the level of both the hypothalamus and anterior pituitary.
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001665:Binding Sites; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone