Effect of corticosterone and dexamethasone on glucocorticoid receptor in lactating rat mammary gland.

Abstract

The effects of either a single dose or long-term administration of corticosterone or dexamethasone 21-acetate (Dex Ac) on glucocorticoid receptor concentration in mammary gland cytosol of lactating adrenalectomized rats were investigated. Adrenalectomy on lactation day 7 failed to affect the glucocorticoid receptors significantly. Both the natural and synthetic steroid caused a rapid decrease of receptor binding in the cytosol but the time course of glucocorticoid receptor depletion was different. Complete depletion of cytosol receptor was observed after both a single s.c. Dex Ac dose (20 micrograms/100 g) and after long-term oral treatment (10 micrograms/ml saline as drinking solution for 6 days) immediately after the last steroid dose. In the first case the depletion was still observable at 24 h after the injection without any change in Kd. In contrast, prolonged administration of Dex Ac maintained the receptor binding low even for 48 h after steroid withdrawal and resulted in an increased Kd. Even after an additional day the binding did not exceed the level of 50% of controls. By that time, however, Kd has returned to normal values. On the other hand, a single dose of corticosterone (100 micrograms/100 g) as well as long-term corticosterone treatment (100 micrograms/ml saline as drinking solution for 6 days) reduced the glucocorticoid receptor concentration only to 60% and 25%, respectively. Twenty four hours after the hormone administration the receptor binding returned to control level, no change in Kd being observed. It was concluded that Dex Ac, but not corticosterone, down-regulates the glucocorticoid receptors in mammary gland cytosol of lactating rats.