Mechanism of Estrogen Action on the Heart

 In Naturopathic News

Node Smith, ND

G Protein-coupled Estrogen Receptor + Heart Physiology

A lot is known about the function of the alpha and beta estrogen receptors. However, less is known about how the G protein-coupled estrogen receptor (GPER) functions. A recent study looked at the mechanism of action of the GPER on heart physiology.1

Estrogens are Very Strong Hormones

Estrogens are very strong hormones that play a role in multiple functions in the body, including the nervous, reproductive, and cardiovascular system.  Because of estrogens’ wide spread action in the body, the awareness of various environmental xenoestrogens – derived from industrial pollutants and natural compounds – has become an increasing concern, as their impact as toxins is becoming increasingly apparent.

Freshwater zebrafish & the effects of estrogens and xenoestrogens

To study the effects of estrogens, and also xenoestrogens, the freshwater zebrafish is often employed. The zebrafish is an established model for the development and function of the human cardiovascular system as well. It is known that endocrine disruptors (xenoestrogens) that mimic estrogens can impact gonad function, but this research suggests these toxins can also impact cardiac function.

Study created 4 Mutant Receptors in Zebrafish in Response to Estrogen

This specific study created 4 mutant receptors in zebrafish that respond to estrogen. The most significant is the GPER which was found to have the most impact on heart rate when dysfunctional. The GPER seems to act autonomously, without the assistance of the other 2 estrogen receptors (alpha or beta) to regulate heart rate. However, the action of the receptor is not on cardiac cells specifically, in fact there are no GPER in the heart, they are primarily located in the brain. This points to a centrally acting effect. It was found that GPER when activated, caused the pituitary to produce more thyroid hormone (T3), which then had the downstream effect of increasing heart rate. GPER mutant fish had a significantly lower basal heart rate.

This connection between thyroid hormone signaling and estrogen paints a complex picture of the effects of environmental estrogens that may have an effect on thyroid and cardiac function, as well as gonadal effects.


  1. Romano SN, Edwards HE, Souder JP, Ryan KJ, Cui X, Gorelick DA. G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish. PLoS Genet. 2017;13(10):e1007069.
Image Copyright: <a href=’’>bigemrg / 123RF Stock Photo</a>

Node Smith, ND, is a naturopathic physician in Portland, OR and associate editor for NDNR. He has been instrumental in maintaining a firm connection to the philosophy and heritage of naturopathic medicine among the next generation of docs. He helped found the first multi-generational experiential retreat, which brings elders, alumni, and students together for a weekend camp-out where naturopathic medicine and medical philosophy are experienced in nature. Four years ago he helped found the non-profit, Association for Naturopathic ReVitalization (ANR), for which he serves as the board chairman. ANR has a mission to inspire health practitioners to embody the naturopathic principles through experiential education. Node also has a firm belief that the next era of naturopathic medicine will see a resurgence of in-patient facilities which use fasting, earthing, hydrotherapy and homeopathy to bring people back from chronic diseases of modern living; he is involved in numerous conversations and projects to bring about this vision.

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