Localization and role of transcortin-like molecules in the anterior pituitary

Abstract

The uptake and binding of [ 3H]dexamethasone and [ 3H] corticosterone in the anterior pituitary has been studied with special reference to the transcortin-like protein and compared with the uptake and binding in the hippocampal region of the rat brain, which lacks this protein. Isolated pituitary cells of adrenalectomized rats contained both glucocorticoid receptors and transcortin-like molecules. A collagenase treatment was used for isolation of the intact pituitary cells. Exposure of cytosol from broken cells of the anterior pituitary to this enzyme destroyed nearly all binding activity for the corticosteroids. The results indicate an intracellular localization of the transcortin-like molecules in the anterior pituitary, although the possibility that plasma transcortin adheres to the cell surface cannot be excluded. Estradiol treatment increased the level of transcortin in the plasma and of transcortin-like molecules in the anterior pituitary. The concentration of the glucocorticoid receptors in the anterior pituitary and the hippocampus remained unaffected. Subcutaneous injection of doses up to 50 μg corticosterone per 100 g body weight did not compete for the binding in vitro of [ 3H]dexamethasone to glucocorticoid receptors in anterior pituitary cytosol. The same doses of corticosterone reduced binding of the synthetic steroid in cytosol of the hippocampus by 40%. Endogenous corticosterone competed poorly for the uptake of [ 3H]dexamethasone in cell nuclei of the anterior pituitary. In cytosol 71% of the receptor sites were still available for [ 3H] dexamethasone binding in vitro. It is proposed that transcortin-like molecules in the anterior pituitary, whether intra- or extracellularly, modulate the effect of corticosterone on pituitary-adrenal activity by mediating the extent of interaction of the steroid with the glucocorticoid receptor.