title: Chronic administration of corticosterone impairs LH signal transduction and steroidogenesis in rat Leydig cells.
abstract: 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 corticosterone plus ovine luteinizing hormone (oLH) (100 microg/kg body weight, s.c., daily) for 15 days. Chronic treatment with corticosterone increased serum corticosterone but decreased serum LH, testosterone, estradiol and testicular interstitial fluid (TIF) testosterone and estradiol concentrations. Administration of LH with corticosterone partially prevented the decrease in 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 corticosterone plus LH treated rats. Activities of steroidogenic enzymes, 3beta- and 17beta-hydroxysteroid dehydrogenase (3beta-HSD and 17beta-HSD) were significantly decreased in corticosterone treated rats. LH plus corticosterone treatment did not affect 3beta-HSD activity but decreased 17beta-HSD activity, indicating a direct inhibitory effect of excess corticosterone on Leydig cell testosterone synthesis. The indirect effect of corticosterone, thus, assume to be mediated through lower LH which regulates the activity of 3beta-HSD. Basal, LH and cAMP-stimulated testosterone production by Leydig cells of corticosterone and corticosterone plus LH treated rats were decreased compared to control suggesting the deleterious effect of excess corticosterone on LH signal transduction and thus steroidogenesis.
authors.affiliation: Department of Endocrinology, Dr. ALM. PG. Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
authors.forename: B R
authors.initials: BR
authors.lastname: Sankar
authors.forename: R R
authors.initials: RR
authors.lastname: Maran
authors.forename: R
authors.initials: R
authors.lastname: Sivakumar
authors.forename: P
authors.initials: P
authors.lastname: Govindarajulu
authors.forename: K
authors.initials: K
authors.lastname: Balasubramanian
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000096:biosynthesis* / Q000097:blood; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
chemical_list: D011974:Receptors, LH; D013256:Steroids; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D000242:Cyclic AMP; C029939:corticosterone acetate; D003345:Corticosterone