Adrenocorticoid-dependent alpha-lactalbumin synthesis in rat mammary gland explants: antagonist studies

Though adrenal steroids are required for the production of alpha-lactalbumin by mammary gland explants, the physiological class of steroid activity (mineralocorticoid, glucocorticoid) remains to be established. alpha-Lactalbumin production by mammary gland explants from mid-pregnant rats has been shown in previous studies to be increased by high doses of aldosterone, but not by deoxycorticosterone; in six of 11 experiments corticosterone, the physiological glucocorticoid in the rat, elevated alpha-lactalbumin; in five other studies corticosterone had no effect. In the present studies the mineralocorticoid antagonist, spirolactone, at very high doses (3-10 mumol/l) blocked the stimulatory effect on alpha-lactalbumin levels of both 30 nmol/l corticosterone and 3 nmol/l RU 26988, a pure synthetic glucocorticoid (Type II) receptor agonist. Receptor studies, however, indicated that this antagonism is consistent with Type II, glucocorticoid receptor occupancy by spirolactone. Since deoxycorticosterone is without agonist effect, and only very high doses of spirolactone affect alpha-lactalbumin synthesis, we conclude that the effect of adrenal steroids on alpha-lactalbumin production is a manifestation of glucocorticoid and not mineralocorticoid activity.