Sex hormone-binding globulin: biomarker and hepatokine?

Trends Endocrinol Metab. 2021 Aug;32(8):544-553. doi: 10.1016/j.tem.2021.05.002. Epub 2021 May 26.


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.

Keywords: de novo lipogenesis; hepatokine; metabolic disease; sex hormone–binding globulin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers
  • Diabetes Mellitus, Type 2* / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Polycystic Ovary Syndrome* / genetics
  • Sex Hormone-Binding Globulin* / genetics


  • Biomarkers
  • Sex Hormone-Binding Globulin