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

Abril Carbajal-García,Luis M Montaño,Jorge Reyes-García,Paola Llanos

doi:10.1155/2020/8849641

Abril Carbajal-García, Luis M Montaño + Show 2 more

Open Access

https://doi.org/10.1155/2020/8849641

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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.

Highlights

Androgen signaling comprises nongenomic and genomic pathways
Cholesterol is the precursor of T, and the steroidogenesis is carried out through cytochrome P450 enzymes [5]. e conversion of cholesterol to pregnenolone is the first step in producing T and is accomplished by the P450 side-chain cleavage enzyme (P450cc/CYP11A1) [4, 5]
We found in the airway smooth muscle (ASM) that T augmented the expression of β2-androgen receptor (AR), favoring an increase in the relaxing response to salbutamol [51]

Summary

Introduction

It is well known that adrenoceptors play a key role in maintaining vascular, airway, and cardiac muscular function In this regard, the modulation by T of the adrenergic receptor signaling pathway has been investigated, and the observed effects appear to be dependent on the studied tissue and the predominance of the adrenergic receptor subtypes either favoring muscle relaxation or contraction [51, 79, 163, 164]. Vasodilator agonists that stimulate GPCRs coupled to the sα subunit (GPCR-sα) such as β1- and β2-ARs, histamine H2, prostaglandin E2, and adenosine A2 receptors, among others [184], induce the synthesis of cAMP and 3′, 5′-cyclic guanosine monophosphate (cGMP); they activate PKA and protein kinase G (PKG), respectively [185], leading to a decrease in the vascular tone [183]. Androgens might play an important role as potential physiological modulators of the ASM tone, facilitating relaxation via β2-AR, and could be a therapeutic alternative for asthma treatment, further research is needed (Figure 3)

Findings

Cardiac Muscle