Effects of 17ß-Estradiol Treatment on Glucose Homeostasis and Aortic Relaxation in Castrated Male Rats

University of the Pacific

With the rising awareness, the number of individuals identifying themselves as transgender in the US is increasing over the years. Cross-sex hormone therapy (CSHT) can alter numerous cardiometabolic parameters leading to the increased risk of cardiovascular diseases (CVD) in transgender population. Epidemiological studies suggest that transgender females (male to female, MtF) on estrogen therapy develop higher risk of CVD compared to transgender males (female to male, FtM) taking testosterone. Underlying mechanisms of impaired cardiovascular functions in MtF are not well documented. Thus, this study was undertaken to elucidate the effects of 17β (E2) on glucose homeostasis and aortic reactivity in castrated (CAS) rats.

The 8-10-weeks old intact male (IM) and CAS rats were implanted subcutaneously with E2 (CAS+E2) or placebo (CAS+PL) containing pellets (~35 days). The glucose tolerance test was performed before sacrificing animals, and the blood was collected to measure the HbA1C levels. Vascular reactivity studies were conducted in aortas using different pharmacological agents to determine the contribution of nitric oxide (NO) to endothelium-dependent vasorelaxation (EDV). Endothelium-independent vasorelaxation and vascular contractile responses were also assessed.

E2 treatment decreased HbA1C levels and improved glucose tolerance in CAS rats. However, the EDV was significantly impaired in aortas from the CAS+E2 group compared to CAS+PL and IM. The impairment of EDV in CAS+E2 rats was accompanied by a significant decrease in NO contribution to vasorelaxation. The smooth muscle sensitivity to NO was not altered, whereas the maximum contractile response was enhanced in aortas of CAS+E2 group compared to IM. In conclusion, CAS+E2 rats showed improved glucose homeostasis, regardless, this group exhibited a decrease in the relative contribution of NO to vasorelaxation. Additional studies are needed to document the direction and magnitude of potential improvement of glucose homeostasis along with the decreased importance of NO to vascular endothelial function in CAS+E2 rats.