Sex difference in glucocorticoid binding in rat pituitary is estrogen dependent

Sex-dependent differences in corticosteroid binding were assessed in individual pituitaries from adult male and female rats that had been adrenalectomized 12 h before sacrifice. Soluble binding was assayed in duplicate on LH-20 columns. Gonadally intact females showed significantly less 3H-dexamethasone binding than did intact males (p less than 0.01). This difference was confirmed in a second study (p less than .001). However, when ovariectomized females were compared with gondadectomized males, there was no difference in receptor concentration. Estrogen was able to reverse the effect of ovariectomy: ovariectomized females receiving estrogen (10 micrograms/rat/day) had significantly fewer receptors than intact males; p less than 0.01). Progesterone (500 micrograms/rat/day) did not antagonize the effect of estrogen in the pituitary. A sex difference was also found in the Type I (mineralocorticoid) receptor subpopulation which comprised approximately 10% of the total receptors, with females having fewer receptors than males. These results demonstrate that in the pituitary, the level of functional corticosteroid receptors is subject to a 20% down-regulation by circulating levels of estrogen. This raises the possibility that the lower number of receptors in females may act to reduce their sensitivity to the negative feedback effects of glucocorticoids at the level of the pituitary.