Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass

A recent study sheds light on how testosterone and cortisol – the body’s primary stress hormone – interact to influence fat accumulation and muscle mass.

The research, conducted in male mice, found that testosterone alone, in the form of dihydrotestosterone (DHT), increases lean mass but does not affect fat mass. In contrast, corticosterone (the mouse equivalent of cortisol) increases fat and decreases lean mass. Interestingly, when DHT and corticosterone are administered together, testosterone helps preserve muscle mass but also amplifies fat gain induced by corticosterone.

This interaction is tissue-specific. In white adipose tissue, the activation of stress-related genes by corticosterone depends on the presence of testosterone. In brown adipose tissue, however, these genes respond to corticosterone independently of testosterone.

Further experiments using mice lacking the androgen receptor (AR) – which mediates testosterone’s effects – showed that corticosterone still increased fat and decreased muscle, even in the absence of AR. This indicates that while testosterone is not essential for the metabolic effects of stress hormones, it does modify the body’s response in a tissue-dependent manner.

These findings highlight the complex interplay between testosterone and stress hormones in regulating metabolism, offering insights into why stress may lead to fat accumulation while sparing muscle, particularly in males. Understanding these mechanisms may inform future strategies to combat stress-related obesity and muscle loss.

Sommers V. et al "Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass" Journal of Endocrinology, 264(3):e240061. doi: 10.1530/JOE-24-0061