title: 11 beta-Hydroxysteroid dehydrogenase and its inhibitors in hypertensive pregnancy.
abstract: Preeclampsia is accompanied by amplification of the sodium retention that is a feature of normal pregnancy. Recent evidence suggests that mineralocorticoid receptor activation is increased in preeclampsia, but classic mineralocorticoids (aldosterone, 11-deoxycorticosterone) are not present in excess. Cortisol can act as a mineralocorticoid receptor agonist only when its renal inactivation to cortisone by 11 beta-hydroxy-steroid dehydrogenase is impaired, for example, in congenital enzyme deficiency and after administration of exogenous inhibitors (eg, licorice). Endogenous inhibitors of this enzyme have been detected in human urine and are increased in pregnancy. To establish whether cortisol causes mineralocorticoid excess in hypertensive pregnancy and whether endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase are responsible, we studied 25 hypertensive pregnant patients (13 with preeclampsia and 12 with gestational hypertension), 16 normotensive pregnant subjects, and 13 nonpregnant control subjects. Concentrations of plasma renin and aldosterone were increased in pregnancy, but less so in hypertensive pregnancy. Plasma potassium and urinary electrolytes were not different between the groups. Plasma cortisol was increased in pregnancy but not different in hypertensive pregnancy, and urinary cortisol, plasma and urinary cortisone, and urinary tetrahydrocortisol and tetrahydrocortisone were not different between the groups. Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase were more active in urine from pregnant women but were not increased further in hypertensive pregnancy. There were no differences in these parameters between patients with preeclampsia and gestational hypertension. We conclude that deficient inactivation of cortisol to cortisone does not contribute to the sodium retention of normotensive or hypertensive pregnancy and that endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase have no evident pathophysiological significance in pregnancy.
authors.affiliation: Department of Medicine, University of Edinburgh, Western General Hospital, Scotland, UK.
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: P M
authors.initials: PM
authors.lastname: Williamson
authors.forename: M A
authors.initials: MA
authors.lastname: Brown
authors.forename: J W
authors.initials: JW
authors.lastname: Honour
authors.forename: C R
authors.initials: CR
authors.lastname: Edwards
authors.forename: J A
authors.initials: JA
authors.lastname: Whitworth
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000097:blood* / Q000172:deficiency; D006973:Hypertension / Q000097:blood / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000201:enzymology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism
chemical_list: D000450:Aldosterone; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin; D006854:Hydrocortisone