Differential regulation of the oxidative 11 beta-hydroxysteroid dehydrogenase activity in testis and liver

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) Type I enzyme is found i n testis and liver. In Leydig cell cultures, 11 beta-HSD activity is report ed to be primarily oxidative while another report concluded that is primari ly reductive. Hepatic 11 beta-HSD preferentially catalyzes reduction and th e reaction direction is unaffected by the external factors. Recent analysis of testicular 11 beta-HSD revealed two kinetically distinct components. In the present study, various steroid hormones or glycyrrhizic acid (GCA), gi ven for 1 week, or thyroxine given for 5 weeks to normal intact rats had di fferent effects on the 11 beta-HSD oxidative activity in testis and liver. Deoxycorticosterone, dexamethasone, progesterone, thyroxine, and clomiphene citrate increased testicular 11 beta-HSD oxidative activity, but decreased hepatic enzyme activity except for deoxycorticosterone (unchanged). Cortic osterone and testosterone decreased 11 beta-HSD oxidative activity in testi s but not that of liver (which was unchanged). Estradiol, GCA and adrenalec tomy lowered oxidative activity of 11 beta-HSD in testis and liver, but the degrees of reduction were different. The in vivo effects of glucocorticoid s too were different, even in the same organ. Dexamethasone, a pure glucoco rticoid, has greater affinity for glucocorticoid receptors (GR) than cortic osterone. The direct effects of dexamethasone via GR in increasing testicul ar 11 beta-HSD oxidative activity may override its indirect effects. Possib ly, the reverse occurs with corticosterone treatment, as it has both glucoc orticoid and mineralocorticoid effects. Because both organs have Type I iso enzyme, the difference in 11 beta-HSD oxidative activities of these two org ans could be attributable to the presence of an additional isozyme in testi s or differences in tissue-specific regulatory mechanisms. (C) 2000 Elsevie r Science Inc, All rights reserved.