Binding and action of glucocorticoids and mineralocorticoids in rabbit mammary gland. Exclusive participation of glucocorticoid type II receptors for stimulation of casein synthesis.
In order to ascertain whether the effect of corticoids upon casein synthesis in pregnant rabbit mammary gland culture is due to interactions with classical glucocorticoid or type I (mineralocorticoid) receptors we have demonstrated the existence of both types of receptors in the tissue and have studied the effects of aldosterone and the specific glucocorticoid agonist RU 28362 upon casein synthesis in tissue culture. Both compounds significantly stimulated prolactin-induced casein synthesis. On dose-response studies RU 28362 proved to be as active as dexamethasone, cortisol was active at intermediate concentrations and aldosterone was the least active. The three glucocorticoids were able to stimulate DNA synthesis in the tissue, but aldosterone had no effect. Finally, RU 486, a potent glucocorticoid antagonist, blocked the action of aldosterone and the other corticoids upon casein synthesis, whereas spironolactone, a mineralocorticoid antagonist, was unable to do so. These results demonstrate that the stimulatory effect of corticoids upon casein synthesis in pregnant rabbit mammary tissue culture is mediated through classical (type II) glucocorticoid receptors. Transferrin accumulation in the tissue was not modified by any treatment, indicating that the action of the steroids was specific for casein, and not a general stimulation of protein synthesis.
D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D002364:Caseins / Q000096:biosynthesis*; D046508:Culture Techniques; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics* / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D008901:Mineralocorticoids / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
D000732:Androstanols; D002364:Caseins; D005938:Glucocorticoids; D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D013148:Spironolactone; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one