Specific inhibition by glucocorticoids of the alpha 2-adrenergic stimulation of adrenocorticotropin release in rat anterior pituitary cells.
Previous studies have shown that a specific alpha 1-adrenergic receptor leads to a 7- to 12-fold stimulation of ACTH release in rat adenohypophyseal cells in culture. The ACTH response to epinephrine is inhibited by 65% after a 3-h incubation with the glucocorticoid agonist dexamethasone, whereas a complete suppression of the response is observed when the steroid is added 4 h earlier. Upon placing the inhibited cells in steroid-free medium, a 50% reversal of the inhibition of the ACTH response is observed after 10 h, whereas normal responsiveness is obtained after 36 h. Glucocorticoid agonists lead to a complete inhibition of epinephrine-induced ACTH secretion with the following order of potencies (ED50 values): triamcinolone acetonide (0.2 nM) much greater than dexamethasone (1.5 nM) much greater than cortisol (11 nM) greater than corticosterone (22 nM). Preincubation with dexamethasone for 4 h leads to an 85% decrease in the maximal ACTH response to epinephrine, whereas the ED50 value of catecholamine action is only slightly increased. Although the activity of the pituitary-adrenocortical axis is highly sex dependent in the rat, 17 beta-estradiol, 5 alpha-dihydrotestosterone, and the pure progestin R5020 have no detectable effect on either basal or epinephrine-induced ACTH release, thus suggesting that sex steroids exert their action in the intact animal at sites other than in corticotrophs. The finding of a specific inhibitory effect of glucocorticoids on epinephrine-induced ACTH secretion lends further support to the suggestion of a physiological role for the pituitary alpha 1-adrenergic receptor in the control of ACTH secretion (at least in the rat). The complete lack of effect of sex steroids indicates the high degree of specificity of the feedback mechanisms controlling ACTH secretion.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D014222:Triamcinolone Acetonide; D003345:Corticosterone; D006854:Hydrocortisone; D004837:Epinephrine