Lifespan Effects of Muscle-specific Androgen Receptor Overexpression on Body Composition of Male and Female Rats

Abstract

Androgenic actions of gonadal testosterone are thought to be a major mechanism promoting sex differences in body composition across the lifespan. However, this inference is based largely on studies of androgen receptor (AR) function in late adolescent or emerging adult rodents. Here we assess body composition and quantify AR expression in skeletal muscle of rats at defined ages, comparing wild-type (WT) to transgenic HSAAR rats which overexpress AR in skeletal muscle. Male and female HSAAR and WT Sprague Dawley rats (N=288) underwent DEXA scanning and tissue collection at post-natal day (PND) 1, 10, 21, 42, 70, 183, 243, and 365. As expected, sex differences in body composition and muscle mass largely onset with puberty (PND-21), with no associated changes to skeletal muscle AR protein. In adulthood, HSAAR increased tibialis anterior (TA) and EDL mass in males, and reduced the expected gain in gonadal fat mass in both sexes. In WT rats, AR protein was reduced in soleus, but not TA, throughout life. Nonetheless, soleus AR protein expression was greater in males than females at all ages of sexual development, yet only at PND-70 in TA. Overall, despite muscle AR overexpression effects, results are inconsistent with major sex differences in body composition during sexual development being driven by changes in muscle AR, but rather suggest that changes in ligand promote sexual differentiation of body composition during pubertal timing. Nonetheless, increased skeletal muscle AR in adulthood can be suffcient to increase muscle mass in males, and reduce adipose in both sexes. This work was supported by an NSERC Grant awarded to D.A.M. (RGPIN 312458). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.