Androgen receptors and muscle: a key mechanism underlying life history trade-offs

Abstract

Sexual dimorphism in skeletal muscle is prominent in mammals, with males typically having larger and stronger muscles than females. Furthermore, neuromuscular systems with sexual functions are remarkably sexually dimorphic in a wide variety of vertebrates. Endocrine mechanisms are of central importance for sexual differentiation of these traits, and anabolic actions of gonadal testosterone have been intensively studied. Here we review the relationship between androgen receptor (AR) and sexual differentiation of neuromuscular systems. We focus our review on the hypotheses that sexual dimorphism and androgen responsiveness of neuromuscular systems is a function of the amount of AR expressed by muscle and that AR in muscle is a key mechanism on which evolution acts to shape individual and species differences in reproductive behavior.

The body region specificity in murine models of muscle regeneration and atrophy

“…Muscle weight and CSA of all limb muscles were remarkably lower in 27-month-old mice compared to 4-month-old mice, whereas head muscles remained unchanged ( Figure 4A-C). Region-specific muscle atrophy was also observed in castrated mouse models, where androgen levels were reduced; the levator ani (LA), bulbospongiosus (BUL) and US muscles were significantly reduced, as reported in previous studies [25][26][27] , whereas the head and limb muscle masses remained unaltered after 2 weeks of castration ( Figure 5A-E). These findings indicate that perineal muscles are more sensitive to an androgen reduction compared to the sensitivity in the head and limb muscles.…”

Evaluating Muscle Mass in Survivors of Acute Respiratory Distress Syndrome: A 1-Year Multicenter Longitudinal Study*

“…Younger age, male sex and lower BMI at enrollment were associated with higher percent lean mass at follow-up. Males have inherently higher circulating androgens, which maintain muscle mass or promote muscle hypertrophy, compared to females[39], and regardless of sex, there is a steady decline in muscle mass with age, with or without fat gains[40]. The association of higher proportion lean mass with lower BMI may be due to greater engagement in weight-bearing activity.…”

Masculinity and the mechanisms of human self-domestication

“…reductions in domesticated masculinity and sexual dimorphism, despite occasionally increased testosterone, may support Cieri et al's (2014) alternative proposition of altered androgen receptor functioning. Although typically ignored in testosterone-focussed studies, varied expression and placement of androgen receptors are crucial moderators of androgen hormone effects(Matsumoto et al, 2013;Monks & Holmes, 2017). These cellular receptors act as both transcription factors-to enable genomic pathways of androgen influence-as well as promoters of rapid transcription-independent androgen response(Matsumoto et al, 2013;Palvimo, 2012).…”

“…These cellular receptors act as both transcription factors-to enable genomic pathways of androgen influence-as well as promoters of rapid transcription-independent androgen response(Matsumoto et al, 2013;Palvimo, 2012). They moderate growth and development of cells and tissues via hyperplasia or hypertrophy (increased number and size of cells, respectively)(Emerson, 2000;Palvimo, 2012), and are distributed as appropriate to taxonomically specific modes of masculine signalling and sexual behaviour; with somatic constraints enforcing a level of optimisation and trade-offs(Monks & Holmes, 2017). As such, whilst fluctuations in circulating testosterone may induce seasonal or lifecycle shifts in masculine traits (including seasonal behaviours), varied distributions of androgen receptors necessarily target these effects to species-relevant features; emphasising the expression of specific sexual morphologies, vocalisations, colourations, and behaviours.Widespread androgenic influence upon NCC-derived masculine features might suggest a synthesis of the androgen receptor(Cieri et al, 2014) and NCC(Wilkins et al, 2014) hypotheses, whereby domestication would dampen the functioning of androgen receptors specifically within NCC-derived tissues.…”