Binding of glucocorticoid antagonists to androgen and glucocorticoid hormone receptors in rat skeletal muscle.
The binding of ten steroids possessing antiglucocorticoid activity has been studied in rat skeletal muscle cytosol. The affinity of these steroids for both the androgen and the glucocorticoid receptors was determined by competition with radioactive R1881 (methyltrienolone, metribolone) and dexamethasone, respectively. The antiglucocorticoid activity of these compounds was assessed in rat hepatoma (HTC) cells by measuring their inhibitory effect on the glucocorticoid-induced tyrosine aminotransferase activity. This led to identification of five novel in vitro glucocorticoid antagonists. All the steroids tested bound to both the glucocorticoid and the androgen receptors in muscle. Four steroids had an affinity for the glucocorticoid receptor higher than for the androgen receptor. The assumption is made that the steroids tested also behave as antagonists when binding to the glucocorticoid receptor in muscle and behave as agonists when binding to the androgen receptor. On this basis, the data allow one to compute a potential anticatabolic (PAG) and a potential anabolic (PAA) index for each compound. These indices might be of predictive value to determine whether these steroids exert their anabolic action in muscle through the glucocorticoid receptor or through the androgen receptor. The data also make it unlikely that satellite cells are a preferential target for anabolic steroids in muscle.
D000728:Androgens / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D004963:Estrenes / Q000378:metabolism; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental; D008297:Male; D015741:Metribolone; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D000728:Androgens; D004963:Estrenes; D005938:Glucocorticoids; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D015741:Metribolone