Glucocorticoid Receptors in Adipose Tissue

Abstract

Although adipose tissue appears to be a target organ for glucocorticoid hormones, previous studies failed to detect glucocorticoid receptors in this tissue. The addition of thioglycerol and Trasylol to the homogenization medium provided an environment in which receptors were successfully demonstrated. [3H]Dexamethasone binding studies were carried out at 0.degree. C in cytosol from various adipose tissues of adrenalectomized rats and bound hormone was separated from free by Sephadex chromatography. Despite the presence of protein protective agents, receptor binding decayed significantly over 24 h but appeared stable from 1 to 5 h. Epididymal fat pad cytosol had an apparent Kd at 0.degree. C for dexamethasone of .apprx. 6 nM and a binding capacity of .apprx. 200 fmol/mg protein. To prove that the receptors were located in fat cells and not in surrounding connective tissue, isolated adipocytes were prepared by collagenase digestion and receptors were demonstrated in the cytosol from these cells as well. The affinity of a series of steroids for the receptor was in the sequence: dexamethasone > corticosterone > progesterone > aldosterone > cortexolone > testosterone > estradiol. Receptors of roughly the same affinity but somewhat fewer binding sites on the basis of cytosol protein were found in other fat depots including peri-renal, peri-scrotal and popliteal. Of interest is the fact that interscapular brown fat and human subcutaneous fat possessed similar receptors. Although [3H]aldosterone also binds to these receptors, the higher competitive capacity of dexamethasone indicated that the binding was to glucocorticoid rather than mineralocorticoid receptors. The data suggest that fat cells contain glucocorticoid receptors which are similar to those seen in other glucocorticoid targets. Presumably these receptors mediate the effects of glucocorticoids on adipose tissue.