Chronic administration of corticosterone impairs LH signal transduction and steroidogenesis in rat Leydig cells

The mechanism involved in the inhibitory actions of chronic corticosterone treatment on Leydig cell steroidogenesis was studied in adult Wistar rats. Rats were treated with corticosterone-21-acetate (2 mg/100 g body weight, i .m., twice daily) for 15 days and another set of rats was treated with cort icosterone plus ovine luteinizing hormone (oLH) (100 mu g/kg body weight, s .c., daily) for 15 days. Chronic treatment with corticosterone increased se rum corticosterone but decreased serum LH, testosterone, estradiol and test icular interstitial fluid (TIF) tcstosterone and estradiol concentrations. Administration of LH with corticosterone partially prevented the decrease i n serum and TIF testosterone and estradiol. Leydig cell LH receptor number, basal and LH-stimulated cAMP production were diminished by corticosterone treatment which remained at control level in the corticostcrone plus LH tre ated rats. Activities of steroidogenic enzymes, 3 beta- and 17 beta-hydroxy steroid dehydrogenase (3 beta-HSD and 17 beta-HSD) were significantly decre ased in corticosterone treated rats. LH plus corticosterone treatment did n ot affect 3 beta-HSD activity but decreased 17 beta-HSD activity, indicatin g a direct inhibitory effect of excess corticosterone on Leydig cell testos terone synthesis. The indirect effect of corticosterone, thus, assume to be mediated through lower LH which regulates the activity of 3 beta-HSD. Basa l, LH and cAMP-stimulated testosterone production by Leydig cells of cortic osterone and corticosterone plus LH treated rats were decreased compared to control suggesting the deleterious effect of excess corticosterone on LH s ignal transduction and thus steroidogenesis. (C) 2000 Elsevier Science Ltd. All rights reserved.