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Endocrine Abstracts (2012) 29 PL8

ICEECE2012 Plenary Lectures Novel molecular link between the circadian clock and hypertension (1 abstracts)

Novel molecular link between the circadian clock and hypertension

H. Okamura


Kyoto University, Kyoto, Japan.


Rhythmic change of the internal milieu is a fundamental principle in all living organisms. A variety of physiological events show daily rhythms, such as blood pressure, hormonal secretion, cell cycle, and migration of stem cells from the bone marrow to the systemic circulation. This timing is determined by the endogenous oscillatory system called the circadian clock. Within the last ten years, the molecular dissection of circadian clock has progressed dramatically, and it is now known that circadian time is generated by clock genes interlocked in an autoregulatory transcription-(post)translational feedback loop operating in most cells of the body. However, the fundamental timing system evolved in a rhythmic environment is now threatened by recent life-style changes: steady day-night (light-dark) cycles are disrupted by shift-works and long working hours, which increases in the risk of life-style related diseases such as hypertension, metabolic syndrome and cancer, caused by such lifestyles. To clearly demonstrate the importance of the biologic clock for health, we used completely arrhythmic mice with deleted Cry1 and Cry2 clock genes (Cry-null mice). Phenotype survey of these animals revealed Cry-null mice rapidly develop salt-sensitive hypertension. By adrenal transcriptome, we identified a new type of 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase (3-β-HSD) that was dramatically over-expressed in Cry-null mice. This enzyme, Hsd3b6, expressed in the zona glomerulosa (ZG), is regulated by the circadian clock. The lack of a functional circadian clock in Cry-null mice leads to Hsd3b6 over-expression, hyperaldosteronism and, ultimately, salt-sensitive hypertension. We further identified HSD3B1 as the human homologue of mouse HSD3B6, and prevalence of this enzyme in a group of human primary aldosteronism, which represents new possibilities in the treatment of hypertension that are being investigated.

Declaration of interest: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however details are not available.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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