Investigating the Effects of Steroid Hormones on G Protein-Coupled Receptors in Vitro

In this project, we investigated the pharmacological effects of steroid hormones on gonadotropin receptors, FSHR and LHR, transiently expressed in HEK293 cells. For this, we used BRET technology to assess receptor-G protein activation as well as -arrestin recruitment upon treatment of cells with gonadotropins, FSH or hCG, in the absence or presence of increasing doses of 3 different steroid hormones (SH), estradiol, testosterone, and progesterone. We observed that SH to different extent significantly modulate FSH/hCG-promoted BRET signals between receptor/G protein as well as receptor/-arrestin pairs. Tis indicate an allosteric mode of action of SH on FSHR and LHR. Moreover, we observed differential effects of SH on receptor/-arrestin pair when comparing FSHR and LHR by decreasing (for FSHR) or increasing (for LHR) the BRET responses. Interestingly, we also observed significant BRET increase with vasopressin (V2R) and angiotensin II (AT1R) receptors. This suggests a more general feature of SH allosterically targeting GPCRs with potential implications in physiology and pathophysiology.