Effects of Cross-Sex Hormone Therapy on Metabolic Parameters and Aortic Relaxation in Castrated Male Rats

Lead Author Affiliation

Pharmacology and Toxicology

Lead Author Status

Doctoral Student

Second Author Affiliation

Pharmacology and Toxicology

Second Author Status

Doctoral Student

Third Author Affiliation

Pharmacology and Toxicology

Third Author Status

Doctoral Student

Fourth Author Affiliation

Veterinary Physiology and Pharmacology

Fourth Author Status

Faculty

Fifth Author Affiliation

Pharmaceutical Sciences and Medicinal Chemistry

Fifth Author Status

Faculty

Sixth Author Affiliation

Physiology and Pharmacology

Sixth Author Status

Faculty

Research or Creativity Area

Pharmacy

Abstract

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) may alter numerous cardiometabolic parameters leading to increased risk of cardiovascular diseases (CVD) in transgender population. However, the effects of CSHT in cardiovascular physiology of males or females are less understood.

Purpose

The current study was undertaken to investigate the effects of 17β-estradiol (E2) treatment on the key 1) cardiometabolic parameters and glucose homeostasis, 2) expression of enzymes and transporters involved in insulin signaling pathway in subcutaneous white adipose tissue (ScWAT), and 3) aortic endothelial and smooth muscle functions in castrated rats (CAS+E2) compared to those in the placebo-treated (CAS+PL) and intact male (IM) rats.

Results

Here we report decreased body weight, visceral white adipose tissue (vWAT) and HbA1C in CAS+E2 group compared to CAS+PL and IM rats. Moreover, E2 treatment improved glucose tolerance, and expressions of p-Akt/Akt and Glut-4 in subcutaneous white adipose tissue (ScWAT) of CAS+E2 rats compared to CAS+PL group. However, CAS+E2 rats exhibited elevated plasma TG level. The endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh) was significantly impaired in the CAS+E2 group possibly due to decreased contribution of nitric oxide (NO)-mediated vasorelaxation and/or increased contractile response to phenylephrine (PE). Nonetheless, the basal NO levels and the smooth muscle sensitivity to NO were not altered.

Significance

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. However, the underlying mechanisms associated with impaired cardiovascular functions in MtF are not well documented. This study, therefore, was undertaken to examine the effects of 17β-estradiol (E2) on certain cardiometabolic parameters and aortic reactivity in castrated (CAS) male rats.

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Effects of Cross-Sex Hormone Therapy on Metabolic Parameters and Aortic Relaxation in Castrated Male Rats

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) may alter numerous cardiometabolic parameters leading to increased risk of cardiovascular diseases (CVD) in transgender population. However, the effects of CSHT in cardiovascular physiology of males or females are less understood.