Premium
STRUCTURE‐ACTIVITY RELATIONSHIP OF VARIOUS CORTICOSTEROIDS ON THE FEEDBACK CONTROL OF CORTICOTROPHIN SECRETION
Author(s) -
JONES M.T.,
TIPTAFT ELIZABETH M.
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb06974.x
Subject(s) - corticosterone , endocrinology , medicine , steroid , chemistry , ene reaction , corticosteroid , secretion , biology , hormone , stereochemistry
1 Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress‐induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour. 2 Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release. 3 Among the steroids tested only 11β, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (corticosterone) and 11β, 14α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 21‐hydroxyl and a 11β‐hydroxyl group. 4 In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21‐hydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycorticosterone), 17α, 21‐dihydroxypregn‐4‐ene‐3, 20‐dione (11‐deoxycortisol), 11β‐hydroxypregn‐4‐ene‐3, 20‐dione (11β‐hydroxyprogesterone) and 11β, 17α‐dihydroxypregn‐4‐ene‐3, 20‐dione (11β, 17α‐dihydroxyprogesterone). Thus, either the 21‐hydroxyl group (e.g. 11‐deoxycorticosterone) or the 11β‐hydroxyl group (e.g. 11β‐hydroxyprogesterone) is sufficient for delayed feedback activity. The 11α‐hydroxyl group, e.g. 11α, 17α, 21‐trihydroxypregn‐4‐ene‐3, 20‐dione (11‐epicortisol) renders the steroid inactive on both feedback mechanisms. 5 18, 21‐Dihydroxypregn‐4‐ene‐3, 20‐dione (18‐hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress‐induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here.