Androgens differentially modulate glucocorticoid effects on adipose tissue and lean mass

Area of Science:

• Endocrinology
• Metabolism
• Molecular Biology

Background:

• Glucocorticoids and androgens have known interactions in metabolic regulation.
• Androgens can enhance glucocorticoid-induced insulin resistance and fat accumulation in male mice.
• The direct role of the androgen receptor (AR) and tissue-specific effects remain unclear.

Purpose of the Study:

• To investigate the impact of androgens on glucocorticoid signaling.
• To determine the tissue-specific effects of androgen deprivation and supplementation on glucocorticoid action.
• To assess the direct contribution of the androgen receptor (AR) to glucocorticoid-mediated metabolic changes.

Main Methods:

• Utilized orchidectomy and chemical castration models for androgen deprivation in male mice.
• Administered dihydrotestosterone (DHT) and corticosterone (CORT) with and without androgen signaling.
• Employed global AR knock-out mice and compared responses to wild-type (WT) littermates upon CORT exposure.

Main Results:

• DHT alone increased lean mass and did not affect fat mass; CORT increased fat mass and decreased lean mass.
• Co-supplementation with DHT counteracted CORT's effect on lean mass but enhanced its effect on adiposity.
• Glucocorticoid-induced gene expression in adipose tissue was androgen-dependent in some tissues but not others; AR knock-out mice showed similar CORT metabolic responses as WT mice.

Conclusions:

• Functional androgen receptor (AR) signaling is not essential for the metabolic effects of glucocorticoids.
• Androgen signaling influences glucocorticoid responses in a tissue-dependent manner, opposing lean mass loss and promoting fat mass gain.