Androgen Effects on the Adrenergic System of the Vascular, Airway, and Cardiac Myocytes and Their Relevance in Pathological Processes

Abstract

Introduction. Androgen signaling comprises nongenomic and genomic pathways. Nongenomic actions are not related to the binding of the androgen receptor (AR) and occur rapidly. The genomic effects implicate the binding to a cytosolic AR, leading to protein synthesis. Both events are independent of each other. Genomic effects have been associated with different pathologies such as vascular ischemia, hypertension, asthma, and cardiovascular diseases. Catecholamines play a crucial role in regulating vascular smooth muscle (VSM), airway smooth muscle (ASM), and cardiac muscle (CM) function and tone. Objective. The aim of this review is an updated analysis of the role of androgens in the adrenergic system of vascular, airway, and cardiac myocytes. Body. Testosterone (T) favors vasoconstriction, and its concentration fluctuation during life stages can affect the vascular tone and might contribute to the development of hypertension. In the VSM, T increases α1-adrenergic receptors (α1-ARs) and decreases adenylyl cyclase expression, favoring high blood pressure and hypertension. Androgens have also been associated with asthma. During puberty, girls are more susceptible to present asthma symptoms than boys because of the increment in the plasmatic concentrations of T in young men. In the ASM, β2-ARs are responsible for the bronchodilator effect, and T augments the expression of β2-ARs evoking an increase in the relaxing response to salbutamol. The levels of T are also associated with an increment in atherosclerosis and cardiovascular risk. In the CM, activation of α1A-ARs and β2-ARs increases the ionotropic activity, leading to the development of contraction, and T upregulates the expression of both receptors and improves the myocardial performance. Conclusions. Androgens play an essential role in the adrenergic system of vascular, airway, and cardiac myocytes, favoring either a state of health or disease. While the use of androgens as a therapeutic tool for treating asthma symptoms or heart disease is proposed, the vascular system is warmly affected.

mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

“…Androgens, especially testosterone, play a key role in cell growth ( Hanson et al 2020 , Stone & Stachenfeld 2020 ). The characteristics of testosterone synthesis and metabolism involve increased protein synthesis, which is essential for normal and hypertrophic growth of cardiomyocytes ( Carbajal-García et al 2020 , Troncoso et al 2021 ). In the present study, ovariectomized SHR decreased blood pressure (mean decrease of 4 mmHg) and improved myocardial hypertrophy after estrogen supplementation.…”

Additive effects of orchiectomy and intermittent hypoxia on lung mechanics and inflammation in C57BL/6J male mice

“…Other effects independent from the airway epithelium have also been described, showing that testosterone increases the synthesis of prostaglandin E 2 , a major airway relaxing mediator (Perusquia et al., 2015). Some data show that testosterone potentiates the relaxation of the airways induced by β‐adrenoreceptor agonists, possibly through inhibition of extra neuronal noradrenaline uptake or of cathecol‐ O ‐methyl transferase, one of the metabolizing enzymes of noradrenaline (see for review; Carbajal‐Garcia et al., 2020b). Finally, chronic testosterone treatment in guinea pigs increases the expression level of the β2‐adrenoreceptor, and this effect is mediated by a genomic mechanism involving the classic form of the nuclear androgen receptor (Carbajal‐Garcia et al., 2020a).…”

Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study

“…Testosterone has also been shown experimentally to have both vasodilatatory and vasoconstrictive properties 33 and both atheroprotective and proatherogenic effects. 34 The hormone's direct effects on vascular tone in the aorta and coronary arteries could influence myocardial performance through alterations in afterload or ischemia, 31 but the extent to which such mechanisms explain the relationship between low cfT and HF documented here is unclear.…”