11 beta-Hydroxysteroid dehydrogenase in the rat placenta: developmental changes and the effects of altered glucocorticoid exposure.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the interconversion of corticosterone, the major glucocorticoid of the rat, and the biologically-inactive 11-dehydrocorticosterone. In the placenta, 11 beta-HSD is thought to regulate glucocorticoid transport between maternal and fetal compartments, and may also affect the local action of glucocorticoids. The present study assessed whether 11 beta-dehydrogenase (corticosterone to 11-dehydrocorticosterone) and 11-oxoreductase (11-dehydrocorticosterone to corticosterone) activities are both present in rat placenta, and whether these activities change with advancing pregnancy. Enzyme activity was estimated on days 16, 19 and 22 of pregnancy (term = day 23) in placental fragments incubated for 6 h with either [3H]corticosterone or [3H]11-dehydrocorticosterone. The percentage conversion of these substrates to [3H]11-dehydrocorticosterone and [3H]corticosterone, respectively, were determined at the end of the incubation. Both 11-oxoreductase and 11 beta-dehydrogenase activities were clearly evident in placental tissue fragments, and while 11-oxoreductase activity declined with advancing pregnancy (P < 0.01), 11 beta-dehydrogenase activity increased (P < 0.01). Thus, 11-oxoreductase exceeded (P < 0.05) 11 beta-dehydrogenase at day 16, but thereafter activities were similar. These changes do not appear to be glucocorticoid-induced, since pretreatment of rats with either metyrapone or dexamethasone acetate from day 15 of pregnancy did not affect placental 11 beta-HSD on day 22.(ABSTRACT TRUNCATED AT 250 WORDS)
Burton
P J
PJ
Department of Anatomy and Human Biology, University of Western Australia, Nedlands, Perth.
Waddell
B J
BJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats
D005938:Glucocorticoids; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D003345:Corticosterone; D008797:Metyrapone