Androgens, Androgen Receptors, and the Skin: From the Laboratory to the Clinic With Emphasis on Clinical and Therapeutic Implications

March 2020 | Volume 19 | Issue 3 | Supplement Individual Articles | 30 | Copyright © March 2020

Published online February 25, 2020

James Q. Del Rosso DO,a Leon H. Kircik MD,b Linda Stein Gold MD,c Diane Thiboutot MDd

aJDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; Touro University Nevada, Henderson, NV bIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University Medical Center, Indianapolis, IN; Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC, Louisville, KY; Skin Sciences, PLLC, Louisville, KY cHenry Ford Health System, Detroit, MI dPenn State University College of Medicine, Hershey, PA

Abstract
The effects of androgens on human skin include growth and differentiation of sebaceous glands, terminal hair growth, epidermal barrier function, wound healing, and modification of the cutaneous microbiome. Androgens exert their activities via ligand formation with intracytoplasmic androgen receptors which can then translocate to the nucleus and interact with genetic androgen response elements to influence signaling cascades. Differences in tissue distribution and activities of enzymes that modify androgen synthesis and catabolism, variations related to gender and ethnicity/race, and genetic polymorphisms that affect androgen receptor functionality directly impact androgen physiology and the pathophysiology associated with a variety of disease states. This manuscript reviews the fundamentals of androgen physiology, androgen synthesis and catabolism in local skin tissue, androgen receptor activity, as well as the impact of genetic polymorphisms and gender. Emphasis is placed on the roles of androgenic activity in sebaceous gland development, sebum production, and the pathophysiology of acne vulgaris.

J Drugs Dermatol. 2020;19(3 Suppl 1):s30-35.

INTRODUCTION

The major steroid sex hormones, androgens and estrogens, play vital roles in maintaining gender characteristics, normal activities of reproductive organs, and other physiologic functions in different organ systems, including skin. Both androgens and estrogens are primarily synthesized in the adrenal glands, ovaries, and testis, and induce their effects via specific intracellular receptor interactions.1 Physiological activities of androgens on human skin include growth and differentiation of sebaceous glands, terminal hair growth, epidermal barrier function, wound healing, and modification of the cutaneous microbiome secondary to presence of sebum.1-4 Interestingly, many skin cells independently exhibit complete enzymatic capability to synthesize androgens de novo from endogenous cholesterol or via conversion of circulating adrenal precursors. Specifically, sebocytes and dermal papilla cells can convert adrenal precursor compounds such as dehydroepiandrosterone sulfate [DHEA-S] and androstenedione into more potent androgens (ie, testosterone [T], dihydrotestosterone [DHT]) via skin-specific isoforms of 5α-reductase enzymes.1,2 Importantly, DHT exhibits the greatest androgenic potency with higher androgen receptor (AR) affinity compared to other androgens and is purely androgenic as it cannot be metabolically aromatized to estrogen.1 In males, DHT is mainly derived from T, while in females, the main precursor of T is androstenedione.3 Homeostatic control of androgen concentrations is via specific enzymes involved in either the synthesis or catabolism of androgens.1

The correlation between sexual maturation and gender with development of androgenetic alopecia (AGA) was recognized by Aristotle as far back as the 4th century BC.2 In the field of dermatology, the role of androgens is widely recognized in association with disorders such as acne vulgaris (AV), AGA, and hirsutism.1-5 Over time, additional research information has become available on androgen tissue metabolism, the roles and locations of specific enzymes involved in androgen physiology, specific tissue activities of androgen hormones, androgen receptor physiology and function, the influences of genetic variability (ie polymorphism) and other factors such as ethnicity and age, impact of anatomic location, and the role of androgens in cutaneous pathophysiology associated with different skin disorders.1-7 Despite extensive research completed over several decades related to androgens and the skin, there is much more to be learned through additional studies about the molecular activities of androgens, their participation in specific skin diseases, androgen receptors, and therapeutic interventions based on identified tissue targets.1-7