Novel effects of deoxycorticosterone on testicular 11 beta-hydroxysteroid dehydrogenase activity and plasma testosterone levels in normal and adrenalectomized rats.

The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) protects the testis from the inhibitory effects of corticosterone on testosterone (T) productio n. The objectives of the present studies were to determine the effects of d eoxycorticosterone (DOC) and its mechanism of actions on testicular 11 beta -HSD activity and plasma T levels after 7 days of treatment. The results re vealed that at the and of 7 days treatment, DOC significantly increased tes ticular 11 beta-HSD activity and plasma T levels in normal rats. However, t he time course showed that high plasma T levels lowered 11 beta-HSD activit y on day 14 and by 21 days both the levels nomalized. In adenalectomized (A DX) rats, only the enzyme activity increased significantly but not plasma T levels Spironolactone, a competitive inhibitor of mineralocorticoid recept or (MR), did not change testicular 11 beta-HSD activity in both normal and DOC treated rats suggesting that DOC did not act through MR in increasing 1 1 beta HSD activity. On the other hand, spironolactone significantly decrea sed plasma T levels in DOC treated rats. Progesterone (P), a competitive in hibitor of glucocorticoid receptors (GR) or corticosterone significantly su ppressed testicular enzyme activity and plasma T levels in DOC treated norm al rats. Carbenoxolone which is an inhibitor of 11 beta-HSD activity signif icantly depressed testicular 11 beta-HSD activity and plasma T levels in DO C treated normal rats. This paper suggests that DOC increased testicular 11 beta-HSD activity through GR; whilst increase in plasma T levels required functioning adrenal glands. The testicular 11 beta-HSD is one of the regula tors of T levels and vice versa.