title: Hypertension due to loss of clock: novel insight from the molecular analysis of Cry1/Cry2-deleted mice.
abstract: In our consumer-oriented society, in which productivity requires around-the-clock activity and demanding shift work, the biologic system that regulates our internal rhythms is being compromised. Poor sleep patterns and hectic lifestyle are detrimental to harmonious physiological and metabolic body systems, with severe impact on public health. Over a trillion peripheral cellular clocks throughout the body, supervised by the master clock located in the hypothalamic suprachiasmatic nucleus, govern most aspects of physiology and behavior. To exemplify the importance of the biologic clock for health, we have recently demonstrated that mice that are arrhythmic because of the deletion of Cry1 and Cry2 clock genes suffer from salt-sensitive hypertension. In these mice, a novel 3β-hydroxyl-steroid dehydrogenase (3β-Hsd) gene under clock control is severely overexpressed specifically in aldosterone-producing cells in the adrenal cortex, leading to hyperaldosteronism and ultimately to salt-sensitive hypertension. The human homologue of this aldosterone-producing, cell-specific enzyme was also characterized and represents a new possibility in the pathogenesis of hypertension.
authors.affiliation: Department of Systems Biology, School of Pharmaceutical Science, Kyoto University, Kyoto, 606, Japan. okamurah@pharm.kyoto-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Fustin
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks; D056926:CLOCK Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D056931:Cryptochromes / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006973:Hypertension / Q000235:genetics*; D051379:Mice
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; D000450:Aldosterone; D015096:3-Hydroxysteroid Dehydrogenases; D056926:CLOCK Proteins