Differential regulation of the oxidative 11beta-hydroxysteroid dehydrogenase activity in testis and liver.
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.
Nwe
K H
KH
Department of Physiology, Faculty of Medicine, National University of Malaysia, Kuala Lumpur. khahhnwe@medic.ukm.my
Hamid
A
A
Morat
P B
PB
Khalid
B A
BA
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000494:pharmacology
D013739:Testosterone; D004958:Estradiol; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone