Fascinating points in the study:
Although SHBG has a crucial influence on circulating bioavailable TES, few studies have considered it as a primary contributor to health status
Sex hormone-binding globulin explained 18.8% of the variation in BMI, which was the largest standardized regression coefficient. This association may indicate that SHBG, although its primary role is its function as a binding protein for TES and other sex steroids in circulation, could also have a more direct function in affecting body composition. While it has been shown that with an increase in FM and insulin serum levels, SHBG concentration is decreased (
Kaufman and Vermeulen, 2005), the biological mechanisms by which this occurs are yet to be determined. Although SHBG is regarded as a binding protein rending SHBG-bound-TES in circulation inactive, even SHBG-bound-TES can have downstream effects via a second messenger by activation of cyclic AMP (
Rosner et al., 1999). There are two binding sites on SHBG, one for steroids, and the other that binds a membrane receptor. When SHBG first interacts with its membrane receptor (e.g., androgen receptor) and then a steroid (e.g., TES, dihydrotestosterone, estradiol) binds to its other receptor (
Rosner et al., 1999), it allows the steroid to exert its effect on the cell without having to enter the cell itself.
Rosner et al. (1999) demonstrated this effect in human prostate explants by initiating a downstream secretion of prostate specific antigen when SHBG was first bound to its membrane androgen receptor and then estradiol was introduced into the tissue. Perhaps when SHBG concentrations are reduced, this type of sequence of events does not occur sufficiently, thereby reducing the downstream effects and resulting in increased FM and circulating insulin, ultimately affecting body composition.