Characteristics of corticosteroid inhibition of adrenocorticotrophin release from the anterior pituitary gland of the rat.
The occurrence and nature of corticosteroid inhibition of ACTH secretion at the rat anterior pituitary gland was investigated using three experimental models: animals bearing lesions of the basal hypothalamus, and two preparations of the gland incubated in vitro; these were tissue segments and collagenase-dispersed cells. Release of ACTH in the experiments was provoked using one of three distinct stimuli: acid extracts of whole hypothalami, corticotrophin releasing activity released by serotonin from hypothalami incubated in vitro and synthetic ovine corticotrophin releasing factor. Irrespective of whether ACTH was measured directly by radioimmunoassay (in the experiments in vitro) or indirectly in terms of corticosterone production (in the lesioned animals), its stimulated release from the anterior pituitary gland was inhibited by corticosterone. Two phases of inhibition were observed; these had some of the characteristics inferred previously from experiments with intact animals and designated fast feedback and delayed feedback. However, the fast feedback demonstrable in lesioned animals did not show the rate-sensitivity shown previously in intact animals. 11-Deoxycortisol (or 11-deoxycorticosterone) and prednisolone proved to be agonists of corticosterone in provoking fast feedback in lesioned animals, whereas they had been shown respectively to act as an antagonist or to have no effect in intact rats. Several steroids were able to cause delayed feedback in lesioned rats, but beclomethasone dipropionate (shown to be an agonist of corticosterone in intact rats) proved to have no inhibitory effect at the anterior pituitary gland of lesioned animals. It is concluded that the dynamics of corticosteroid feedback mechanisms at the anterior pituitary gland, as indicated by experiments in lesioned animals, differ from those operative in the intact animals. Other work suggests that a more important site for such inhibitory mechanisms in vivo is the hypothalamus.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001507:Beclomethasone / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003864:Depression, Chemical; D003900:Desoxycorticosterone / Q000494:pharmacology; D005246:Feedback; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013312:Stress, Physiological; D014020:Tissue Extracts / Q000494:pharmacology
D014020:Tissue Extracts; D012701:Serotonin; D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011239:Prednisolone; D001507:Beclomethasone; D003345:Corticosterone