Sex hormone-binding globulin (SHBG) is a glycoprotein that binds to androgens and estrogens. SHBG is found in all vertebrates apart from birds. SHBG inhibits the function of these hormones. Thus, the local bioavailability of sex hormones is influenced by the level of SHBG. SHBG’s production is regulated under the influence of FSH on Sertoli cells, enhanced by insulin, retinol, and testosterone. The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone. SHBG levels are usually about twice as high in women than in men. In women, SHBG serves to limit exposure to both androgens and estrogens. Low SHBG levels in women have been associated with hyperandrogenism and endometrial cancer due to heightened exposure to androgens and estrogens, respectively. During pregnancy, due to activation of SHBG production in the liver by high estrogen levels, SHBG levels increase by five-fold to ten-fold.
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