Chronic Corticosterone Treatment Impairs Leydig Cell 11β-Hydroxysteroid Dehydrogenase Activity and LH-Stimulated Testosteorne Production

The effects of excess corticosterone on luteinizing hormone (LH)-stimulated Leydig cell testosteorne production and activity of 11β-HSD was studied. Adult male rats (200-250 g body weight) were treated with corticosterone-21-acetate (2 mg/100 g body weight, i.m., twice daily) for 15 days. Another set of rats was treated with corticosterone (dose as above) plus LH (ovine LH 100 µg/kg body weight, s.c., daily) for 15 days. Corticosterone administration significantly increased serum and testicular interstitial fluid (TIF) corticosterone but decreased testosteorne levels. Administration of LH with corticosterone partially prevented the decrease in serum and TIF testosteorne. The oxidative activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) was significantly decreased in Leydig cells of rats treated with corticosterone alone and in combination with LH. The direct effect of corticosterone on Leydig cell steroidogenic potency was also studied in vitro. Addition of corticosterone to Leydig cell culture showed a dose dependent effect on LH-stimulated testosteorne production. Corticosterone at 50 and 100 ng/ml did not alter LH-stimulated testosteorne production, but at high doses (200-400 ng/ml), decreased basal and LH-stimulated testosteorne production. Basal and LH-stimulated cAMP production was not altered by corticosterone in vitro. It is concluded from the present study that elevated levels of corticosterone decreased the oxidative activity of 11β-HSD and thus resulting in impaired Leydig cell steroidogenesis and the inhibitory effects of corticosterone on testosteorne production appear to be mediated through inhibition of LH signal transduction at post-cAMP level.

Key words

Leydig Cell - Corticosterone - Testosteorne - 11β-HSD - cAMP