Testosterone signals not only through the nuclear AR, but also through mARs, including ZIP9 and GPRC6A. It has been proposed that differential signaling through mARs may be involved in the dissociation of the anabolic and androgenic effects of AAS. Indeed, DHT has less than 1% of the affinity of testosterone for ZIP9, and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly. This indicates that AAS do show differential interactions with the AR and mARs. However, women with complete androgen insensitivity syndrome (CAIS), who have a 46,XY ("male") genotype and testes but a defect in the AR such that it is non-functional, are a challenge to this notion. They are completely insensitive to the AR-mediated effects of androgens like testosterone, and show a perfectly female phenotype despite having testosterone levels in the high end of the normal male range. These women have little or no sebum production, incidence of acne, or body hair growth (including in the pubic and axillary areas). Moreover, CAIS women have lean body mass that is normal for females but is of course greatly reduced relative to males. These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens.Rahwan, R. G. (1988). The Pharmacology of Androgens and Anabolic Steroids. American Journal of Pharmaceutical Education, 52(2), 167–177. The mARs have however been found to be involved in some of the health-related effects of testosterone, like modulation of prostate cancer risk and progression.
