Hormonal Regulation of Estrogen Receptors

Abstract

BackgroundWe previously showed that estrogen has beneficial effects on cardiovascular function via the novel G‐protein coupled estrogen receptor (GPER). Selectively activating GPER may elicit beneficial cardiovascular effects of estrogen without eliciting deleterious effects. Receptor expression is important in developing targeted pharmacological therapies, but the regulation and expression of estrogen receptors is still not fully understood.ObjectiveOur goal was to study the effects androgens, glucocorticoids, and progesterone on the expression of the classical estrogen receptor ERα and novel estrogen receptor GPER.MethodsMouse aortic smooth muscle cells (MOVAS) were grown in 10% FBS media to 80% confluency and then starved for 24 h in charcoal‐stripped 0.5% FBS. The plates were treated for 24 h with 100 nm of dexamethasone (DEX), dihydrotestosterone (DHT), medroxyprogesterone acetate (MPA), or vehicle. After treatment, RNA was extracted and droplet digital PCR was used to quantify the expression of both GPER and ERα. Results were analyzed using a one‐way ANOVA.ResultsGPER expression was decreased by both DHT (66% of control, p=0.006, n=9) and MPA (70% of control, p=0.012, n=6). The impact of DEX on GPER was not statistically significant (89% of control, p=0.245, n=9). ERα expression was significantly reduced by DEX (65% of control, p=0.0046, n=9), DHT (56% of control, p=0.004, n=9), and MPA (52% of control, p=0.005, n=6) as compared to controls.ConclusionsIn cultured vascular smooth muscle cells, DHT and MPA decreased the expression GPER, while DEX, DHT, and MPA downregulated ERα. These results suggest that androgens, glucocorticoids, and progesterone act at the transcriptional level to decrease the expression of GPER and ERα. This decrease in receptor expression could lessen beneficial effects of GPER and/or ERα on cardiovascular function. Future studies will address the impact of androgens, glucocorticoids, and progesterone on the molecular mechanisms and in vivo cardiovascular responses to estrogen. The regulation of estrogen receptor expression is important for understanding the clinical interactions that may alter the response to hormone therapy.Support or Funding InformationFunding was provided by NIH HL133619 to SHL.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.