1. Sex steroids have been shown to regulate the biosynthesis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11 beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar rats was determined following a daily IM injection of sex steroids for 7 days. 4. The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T in normal and ADX rats. The enzyme activity in normal rats given both T and E2 was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The presence of corticosteroids influenced the effects of E2, but not of T and P4, on 11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4 increased it. E2 did not act through lowering T level.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) protects the testis from the inhibitory effects of corticosterone on testosterone (T) production. The objectives of the present studies were to determine the effects of deoxycorticosterone (DOC) and its mechanism of actions on testicular 11beta-HSD activity and plasma T levels after 7 days of treatment. The results revealed that at the end of 7 days treatment, DOC significantly increased testicular 11beta-HSD activity and plasma T levels in normal rats. However, the time course showed that high plasma T levels lowered 11beta-HSD activity on day 14 and by 21 days both the levels normalized. In adrenalectomized (ADX) rats, only the enzyme activity increased significantly but not plasma T levels. Spironolactone, a competitive inhibitor of mineralocorticoid receptor (MR), did not change testicular 11beta-HSD activity in both normal and DOC treated rats suggesting that DOC did not act through MR in increasing 11beta-HSD activity. On the other hand, spironolactone significantly decreased plasma T levels in DOC treated rats. Progesterone (P), a competitive inhibitor of glucocorticoid receptors (GR) or corticosterone significantly suppressed testicular enzyme activity and plasma T levels in DOC treated normal rats. Carbenoxolone which is an inhibitor of 11beta-HSD activity significantly depressed testicular 11beta-HSD activity and plasma T levels in DOC treated normal rats. This paper suggests that DOC increased testicular 11beta-HSD activity through GR; whilst increase in plasma T levels required functioning adrenal glands. The testicular 11beta-HSD is one of the regulators of T levels and vice versa.
The effects of stress and corticosterone on testicular 11beta-hydroxysteroid dehydrogenase (11beta-HSD) oxidative activity have been controversial, whilst that of adrenocorticotrophic hormone (ACTH) have not been investigated before. Hence, the aim of the present study was to determine the in vivo effects of stress due to injection and sham operation, ACTH and corticosterone on testicular and hepatic 11beta-HSD oxidative activity and plasma testosterone levels in normal and adrenalectomized (ADX) rats and their possible mechanism of actions. Adrenalectomy reduced both testicular 11beta-HSD oxidative activity and plasma testosterone levels. The effects of injection and sham operation significantly increased plasma corticosterone levels with decreased testicular 11beta-HSD oxidative activity and plasma testosterone levels in normal but not in ADX rats. Likewise. ACTH or corticosterone treatment for 7 days decreased both testicular 11beta-HSD oxidative activity in a dose dependent manner and plasma testosterone levels in normal rats; but the values in ADX rats remained unchanged. However, none of the above values were significantly lower than that of the ADX levels. Corticosterone seems to maintain testicular 11beta-HSD oxidative activity within the range between normal and ADX rats. These changes are not attributable to diurnal rhythms, as the time of sacrifice has been fixed between 8:30 and 10:30 am. In the liver, no significant change in 11beta-HSD oxidative activity was observed with sham operation, ACTH or corticosterone treatment; but adrenalectomy significantly decreased it. In conclusion, in the intact normal rats, stress, ACTH or corticosterone modulates testicular (but not hepatic) 11beta-HSD oxidative activity indirectly through the adrenal glands and the physiological level of corticosterone is ideal for normal reproductive functions.
11Beta-hydroxysteroid dehydrogenase (11beta-HSD) Type I enzyme is found in testis and liver. In Leydig cell cultures, 11beta-HSD activity is reported to be primarily oxidative while another report concluded that is primarily reductive. Hepatic 11beta-HSD preferentially catalyzes reduction and the reaction direction is unaffected by the external factors. Recent analysis of testicular 11beta-HSD revealed two kinetically distinct components. In the present study, various steroid hormones or glycyrrhizic acid (GCA), given for 1 week, or thyroxine given for 5 weeks to normal intact rats had different effects on the 11beta-HSD oxidative activity in testis and liver. Deoxycorticosterone, dexamethasone, progesterone, thyroxine, and clomiphene citrate increased testicular 11beta-HSD oxidative activity, but decreased hepatic enzyme activity except for deoxycorticosterone (unchanged). Corticosterone and testosterone decreased 11beta-HSD oxidative activity in testis but not that of liver (which was unchanged). Estradiol, GCA and adrenalectomy lowered oxidative activity of 11beta-HSD in testis and liver, but the degrees of reduction were different. The in vivo effects of glucocorticoids too were different, even in the same organ. Dexamethasone, a pure glucocorticoid, has greater affinity for glucocorticoid receptors (GR) than corticosterone. The direct effects of dexamethasone via GR in increasing testicular 11beta-HSD oxidative activity may override its indirect effects. Possibly, the reverse occurs with corticosterone treatment, as it has both glucocorticoid and mineralocorticoid effects. Because both organs have Type I isoenzyme, the difference in 11beta-HSD oxidative activities of these two organs could be attributable to the presence of an additional isozyme in testis or differences in tissue-specific regulatory mechanisms.