Research Suggests New Pathways For Hyperaldosteronism

Source: Sanford Burnham Prebys Medical Discovery Institute

Summary: Researchers in a new study, identified a mechanism that explains the development of hyperaldosteronism, which is responsible for the majority of secondary hypertension.

Secondary hypertension is a high blood pressure (BP) caused by another medical condition. About 10% of the people with high BP have secondary hypertension. In these cases, when the root cause is treated, BP usually returns to normal or significantly lowered. One of the most common causes of secondary hypertension is hyperaldosteronism, a condition in which the adrenal glands produce too much aldosterone. Researchers from Sanford Burnham Prebys Medical Discovery Institute have identified a mechanism that explains the development of hyperaldosteronism. These study results offer a path for drug discovery to treat the condition. The research findings were published in the journal JCI Insight.

 medical condition wherein too much aldosterone is produced by the adrenal glands

Ze’ev Ronai, Ph.D., chief scientific advisor, Professor, Tumor Initiation and Maintenance Program, SBP. Credit: Sanford Burnham Prebys Medical Discovery Institute

Aldosterone is a hormone, which balances potassium and sodium levels in the blood. In hyperaldosteronism, too much aldosterone is produced which leads to lower levels of potassium and higher levels of sodium. Excess sodium leads to water retention, increasing the blood volume and blood pressure. The researchers found that the adrenal glands of mice lacking the Siah1 Ubiquitin Ligase Gene was markedly different and had increased levels of aldosterone. Upon, further examination they noted elevated levels of PIAS1 (a Siah1 controlled protein) acts as a key regulator of cholesterol biosynthesis, the precursor for aldosterone synthesis. These results are the first to identify the role of this gene in hyperaldosteronism.

Senior author, Ze’ev Ronai said, “Our research, based on a genetic model, identifies an unexpected layer in the regulation of adrenal gland development and in hyperaldosteronism”, “The findings are important because they identify a previously unknown regulatory axis that controls aldosterone levels, thus offering new avenues for drug discovery of secondary hypertension.”

More Information: Marzia Scortegagna et al, “The E3 ubiquitin ligase Siah1 regulates adrenal gland organization and aldosterone secretion”, JCI insight (2017). 10.1172/jci.insight.97128

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