Regulation of 11 beta-hydroxysteroid dehydrogenase by sex steroids in vivo: further evidence for the existence of a second dehydrogenase in rat kidney.
11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyses the reversible conversion of corticosterone to inactive 11-dehydrocorticosterone, thus regulating glucocorticoid access to mineralocorticoid and perhaps glucocorticoid receptors in vivo. 11 beta-OHSD has been purified from rat liver and an encoding cDNA isolated from a liver library. However, several lines of indirect evidence suggest the existence of at least two isoforms of 11 beta-OHSD, one found predominantly in glucocorticoid receptor-rich tissues and the other restricted to aldosterone-selective mineralocorticoid target tissues and placenta. Here we have examined the effects of chronic (10 day) manipulations of sex-steroid levels on 11 beta-OHSD enzyme activity and mRNA expression in liver, kidney and hippocampus and present further evidence for the existence of a second 11 beta-OHSD isoform in kidney. Gonadectomized male and female rats were given testosterone, oestradiol or blank silicone elastomer capsules, controls were sham-operated. In male liver, gonadectomy+oestradiol treatment led to a dramatic decrease in both 11 beta-OHSD activity (69 +/- 8% decrease) and mRNA expression (97 +/- 1% decrease). Gonadectomy and testosterone replacement had no effect on male liver 11 beta-OHSD. However, in female liver, where 11 beta-OHSD activity is approximately 50% of that in male liver, gonadectomy resulted in a marked increase in 11 beta-OHSD activity (120 +/- 37% rise), which was reversed by oestradiol replacement but not testosterone treatment. In male kidney, gonadectomy+oestradiol treatment resulted in a marked increase in 11 beta-OHSD activity (103 +/- 4% rise). By contrast, 11 beta-OHSD mRNA expression was almost completely repressed (99 +/- 0.1% decrease) by oestradiol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Low
S C
SC
Department of Medicine, University of Edinburgh, Western General Hospital, U.K.
Assaad
S N
SN
Rajan
V
V
Chapman
K E
KE
Edwards
C R
CR
Seckl
J R
JR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006624:Hippocampus / Q000201:enzymology; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases