A cellular doorkeeper’s role in hypertension

From their perch atop the kidneys, the adrenal glands help to control blood pressure by secreting the hormone aldosterone. In aldosteronism, often caused by adrenal tumors called adenomas, excessive levels of this hormone cause severe hypertension, but the mechanisms of tumor-induced aldosteronism have been poorly understood.

In the February 11 issue of Science, a team led by Richard P. Lifton, M.D., Ph.D., chair and Sterling Professor of Genetics, reports that many adenomas carry mutations in the gene KCNJ5, which encodes channels that selectively allow potassium ions through cell membranes. The mutated channels are less selective, allowing sodium to enter and unleashing a signaling cascade that causes adenoma cells to secrete aldosterone and to overproliferate. A KCNJ5mutation was also found in a family with aldosteronism not caused by adenomas, suggesting that these mutations can also cause noncancerous adrenal cells to overproliferate and secrete too much aldosterone.

“This gene was not on anybody’s list to sequence in an investigation of this disease,” Lifton says. “We really hit the jackpot.”