Effects of 17β-Estradiol Treatment on Metabolic Function and Aortic Relaxation in Castrated Male Rats

Exogenous estrogen use in male-to-female individuals has been linked to increased cardiovascular disease risk, though the mechanisms remain unclear. This study examines the effects of 17β-estradiol (E₂) on metabolic and aortic function in castrated (CAS) male Sprague Dawley rats. CAS rats received subcutaneous E₂ (CAS + E₂) or placebo (CAS + PL) pellets for ~35 days, with intact males serving as controls. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine and contractile responses to phenylephrine were measured in aorta before and after pharmacological inhibitors. Metabolic parameters and expression of proteins associated with vascular and insulin signaling were also determined in aorta and white adipose tissue (WAT). E₂ treatment reduced body weight, improved HbA1c and enhanced glucose tolerance in CAS rats compared to the CAS + PL group. Improved glucose homeostasis was associated with upregulation of estrogen receptor alpha, phosphorylated Akt/Akt, and glucose transporter-4 expression in WAT. However, E₂ increased plasma triglyceride and impaired EDV, indicating compromised vascular function. Our results suggest that impaired aortic relaxation in the CAS + E₂ group may be partly attributable to increased contractility. Additionally, we observed reduced G protein-coupled estrogen receptor and elevated inducible nitric oxide synthase expression, warranting further investigation into whether these factors contribute to the effects of E₂ on aortic relaxation.