Classic and Novel Sex Hormone Binding Globulin Effects on the Cardiovascular System in Men

Figure 1

Signaling pathways activated by SHBG. The figure illustrates the action mechanism of SHBG as a hormone carrier and SHBG direct actions. (1) Free circulating androgens and estrogens that correspond to the bioavailable portion of sex hormones can cross the plasma membrane and bind intracellular sex hormone receptors, thus activating the “classic,” genomic sex hormone intracellular pathways. (2) As described in the literature, free circulating sex hormones can also bind to putative membrane receptors activating “fast, nongenomic intracellular signaling pathways.” (3) Another putative membrane receptor, for SHBG, can also activate intracellular signaling pathways, leading to fast, nongenomic effects. (4) The megalin receptor, which induce the internalization of SHBG and a retrograde pathway that affects nuclear and mitochondrial function, can also account for some SHBG-induced intracellular effects.