Sex hormone–binding globulin: biomarker and hepatokine?

A recent genome-wide association study has identified a cluster of de novo lipogenesis genes that affect serum sex hormone–binding globulin (SHBG) levels. A recent Mendelian randomization study has shown that SHBG functions as a true hepatokine, at least in women, by reducing the risk of type 2 diabetes. SHBG-raising therapies, such as inhibitors of de novo lipogenesis or thyroid hormone receptor beta agonists, may provide promising future directions for the treatment and prevention of type 2 diabetes and polycystic ovary syndrome. Over the past decade, there have been important breakthroughs in our understanding of the regulation and function of sex hormone–binding globulin (SHBG). A recent genome-wide association and Mendelian randomization study has provided new insights at the population level. Thorough study of genetic variants affecting serum SHBG has identified de novo lipogenesis as one of the mechanistic links between the metabolic syndrome and reduced serum SHBG levels in humans. Furthermore, careful deduction of the Mendelian randomization results suggests a direct, causal role for SHBG in the pathogenesis of type 2 diabetes, as a hepatokine, in women. These findings prompt the development of SHBG-raising therapies as a means to prevent or treat disorders such as type 2 diabetes and polycystic ovary syndrome. Over the past decade, there have been important breakthroughs in our understanding of the regulation and function of sex hormone–binding globulin (SHBG). A recent genome-wide association and Mendelian randomization study has provided new insights at the population level. Thorough study of genetic variants affecting serum SHBG has identified de novo lipogenesis as one of the mechanistic links between the metabolic syndrome and reduced serum SHBG levels in humans. Furthermore, careful deduction of the Mendelian randomization results suggests a direct, causal role for SHBG in the pathogenesis of type 2 diabetes, as a hepatokine, in women. These findings prompt the development of SHBG-raising therapies as a means to prevent or treat disorders such as type 2 diabetes and polycystic ovary syndrome. the formation of fatty acids from non-lipid precursors, such as glucose. this hypothesis states that the biological effect of a hormone, such as testosterone, is the result of the unbound or free fraction rather than the total concentration of the hormone. a liver-derived, signaling protein that affects systemic metabolism. a statistical method that uses genetic variants as instruments to study the causal association between an exposure and outcome.