SHBG

Sex hormone-binding globulin (SHBG) is a liver-derived glycoprotein that circulates in blood as a high-affinity binder of sex steroids. It functions as a transport protein, forming dimers that bind testosterone, dihydrotestosterone (DHT), and estradiol, with testosterone and DHT binding in particular. The majority of circulating hormones are bound to SHBG or albumin, while only a small free fraction is biologically active at tissue receptors. SHBG thus modulates the bioavailability and tissue exposure to these hormones and can act as a reservoir that releases hormone when needed.

Production and binding characteristics vary by sex and physiology. SHBG is synthesized mainly by hepatocytes, and serum levels are influenced by hormonal and metabolic state. Estrogens raise SHBG production, whereas androgens tend to lower it. Thyroid hormone increases SHBG, while insulin resistance and obesity tend to decrease it. Pregnancy and certain hormone therapies can markedly raise SHBG. Age and liver function also affect SHBG levels, with notable changes across the lifespan.

Clinical relevance and use in medicine. SHBG measurements are commonly interpreted alongside total testosterone to estimate free testosterone, often using calculation methods. Low SHBG is associated with obesity, insulin resistance, and polycystic ovary syndrome, while high SHBG occurs with estrogen exposure and certain thyroid states. Genetic variation in the SHBG gene can influence circulating levels and hormone binding. SHBG levels help clinicians assess androgen status and interpret hormonal profiles in both men and women.

Genetics. The SHBG gene is located on chromosome 17p13 and encodes the SHBG protein; multiple polymorphisms affect circulating levels and binding affinity, contributing to individual differences in hormone bioavailability.