Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy - PubMed (original) (raw)
Comment
Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy
D S Geller et al. Science. 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.
Comment on
- Hypertension. Mutation points to salt recycling pathway.
Wickelgren I. Wickelgren I. Science. 2000 Jul 7;289(5476):23-6. doi: 10.1126/science.289.5476.23b. Science. 2000. PMID: 10928921 No abstract available.
Similar articles
- Hypertension. Mutation points to salt recycling pathway.
Wickelgren I. Wickelgren I. Science. 2000 Jul 7;289(5476):23-6. doi: 10.1126/science.289.5476.23b. Science. 2000. PMID: 10928921 No abstract available. - The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related.
Rafestin-Oblin ME, Souque A, Bocchi B, Pinon G, Fagart J, Vandewalle A. Rafestin-Oblin ME, et al. Endocrinology. 2003 Feb;144(2):528-33. doi: 10.1210/en.2002-220708. Endocrinology. 2003. PMID: 12538613 - Identification of steroid ligands able to inactivate the mineralocorticoid receptor harboring the S810L mutation responsible for a severe form of hypertension.
Pinon GM, Fagart J, Souque A, Auzou G, Vandewalle A, Rafestin-Oblin ME. Pinon GM, et al. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):181-8. doi: 10.1016/j.mce.2003.10.053. Mol Cell Endocrinol. 2004. PMID: 15134816 - Evolution of hormone selectivity in glucocorticoid and mineralocorticoid receptors.
Baker ME, Funder JW, Kattoula SR. Baker ME, et al. J Steroid Biochem Mol Biol. 2013 Sep;137:57-70. doi: 10.1016/j.jsbmb.2013.07.009. Epub 2013 Jul 29. J Steroid Biochem Mol Biol. 2013. PMID: 23907018 Review. - [Genetic disorders caused by gain or loss of function of the mineralocorticoid receptor].
Arai K, Shibasaki T. Arai K, et al. Nihon Rinsho. 2002 Feb;60(2):361-6. Nihon Rinsho. 2002. PMID: 11857927 Review. Japanese.
Cited by
- Genetic background of neonatal hypokalemia.
Fang C, Zhou W. Fang C, et al. Pediatr Nephrol. 2024 Sep 16. doi: 10.1007/s00467-024-06492-5. Online ahead of print. Pediatr Nephrol. 2024. PMID: 39283520 Review. - Monogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System.
Özdede M. Özdede M. Anatol J Cardiol. 2024 Jun 14;28(9):417-28. doi: 10.14744/AnatolJCardiol.2024.4480. Online ahead of print. Anatol J Cardiol. 2024. PMID: 38872497 Free PMC article. - Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease.
Reppe S, Gundersen S, Sandve GK, Wang Y, Andreassen OA, Medina-Gomez C, Rivadeneira F, Utheim TP, Hovig E, Gautvik KM. Reppe S, et al. Int J Mol Sci. 2024 May 20;25(10):5554. doi: 10.3390/ijms25105554. Int J Mol Sci. 2024. PMID: 38791593 Free PMC article. - Genetics of Hypertension: From Monogenic Analysis to GETomics.
Zappa M, Golino M, Verdecchia P, Angeli F. Zappa M, et al. J Cardiovasc Dev Dis. 2024 May 18;11(5):154. doi: 10.3390/jcdd11050154. J Cardiovasc Dev Dis. 2024. PMID: 38786976 Free PMC article. Review. - Update in genetic and epigenetic causes of hypertension.
Mani A. Mani A. Cell Mol Life Sci. 2024 Apr 30;81(1):201. doi: 10.1007/s00018-024-05220-4. Cell Mol Life Sci. 2024. PMID: 38691164 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases