11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action.
In normal physiology 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the mineralocorticoid receptor (MR) from glucocorticoid excess. In the rat, however, 11 beta-OHSD mRNA and activity is widespread, suggesting that it may also play a role in regulating ligand access to the glucocorticoid receptor (GR). We have studied the role of the 11 beta-OHSD in modulating corticosteroid hormone action in rat pituitary GH3 cells (glucocorticoids inhibit prolactin gene transcription) and renal epithelial NRK-52E cells (mineralocorticoids increase Na-K ATPase subunit gene expression) in culture. Both cell lines express high levels of 11 beta-OHSD activity, and Northern/Western blot analyses using a rat cDNA probe and antisera raised against rat liver 11 beta-OHSD reveal a single 1.4 Kb mRNA encoding an enzyme of molecular size 34 kDa. In GH3 cells, prolactin gene transcription was unaffected by corticosterone (B) in doses of 10(-8) to 10(-6) M. When 11 beta-OHSD activity was inhibited with the licorice derivative, glycyrrhetinic acid (GE); however, 10(-6) M B inhibited prolactin (PRL) mRNA levels to the same degree as an equimolar concentration of the GR agonist RU 28362. This effect was blocked by co-incubation with the GR antagonist RU 38486. In NRK-52E cells, co-incubation with B and GE resulted in a marked increase in alpha 1/beta 1 Na-K ATPase subunit mRNA levels when compared with GE and/or B alone and this effect could be blocked by administration of the MR antagonist RU 26752.(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
P M
PM
University of Birmingham, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, United Kingdom.
Whorwood
C B
CB
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney; D010902:Pituitary Gland / Q000378:metabolism; D011388:Prolactin / Q000235:genetics; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
D000305:Adrenal Cortex Hormones; D011388:Prolactin; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000254:Sodium-Potassium-Exchanging ATPase; D003345:Corticosterone