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Activating Mineralocorticoid Receptor Mutation in Hypertension Exacerbated by Pregnancy
- Source :
- Science. July 7, 2000, Vol. 289 Issue 5476, 119
- Publication Year :
- 2000
-
Abstract
- Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.<br />Although blood pressure is normally reduced throughout gestation, about 6% of pregnancies are complicated by the development of hypertension, raising the risk of pre-eclampsia, a hypertensive disorder of pregnancy that [...]
Details
- Language :
- English
- ISSN :
- 00368075
- Volume :
- 289
- Issue :
- 5476
- Database :
- Gale General OneFile
- Journal :
- Science
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.63604564