March 2, 2023

Sex-specific regulation of kidney signals

Links between estrogen signaling and sodium excretion by the kidney could help explain a reduced risk of hypertension in females versus males.

Before menopause, women have decreased risk of developing cardiovascular diseases, such as hypertension, compared to men. This sex-specific protection has been largely attributed to estrogens, although the mechanisms remain a topic of investigation. 

The kidney maintains blood pressure in part by controlling urine sodium excretion via the renal endothelin-1 (ET-1) signaling system, and an estrogen receptor called GPER1 is suggested to be involved in this process. 

To investigate this potential pathway, Eman Gohar, PhD, and colleagues studied mice with and without GPER1 expression. In mice with GPER1, females excreted more ET-1 than males; however, this sex difference was lost in mice without GPER1. Immunostaining of the kidneys revealed increased ET-1 storage in the renal cortex tubular cells of female mice without GPER1, limiting the release of ET-1 into the urine.  

The article, published in Frontiers in Physiology, suggests that GPER1 is a sex-specific regulator of the renal ET-1 excretion system, potentially explaining the decreased hypertension risk of females versus males.

Co-authors include Ginger Guthrie, Rawan Almutlaq, Maryam Butt, and David Pollock, PhD, at the University of Alabama at Birmingham, and Sho Sugahara, MD, PhD, and Craig Brooks, PhD, in the Division of Nephrology and Hypertension at VUMC. 

This research was supported by the National Institutes of Health (grant DK119413) and the University of Alabama at Birmingham Science and Technology Honors Program Scholarship.