Sex hormone regulation (SHBG)

Sex hormone-binding globulin is a steroid-binding protein that is affected by various factors such as age and can serve as an indicator of endocrine disorders or metabolic diseases.

The female sex hormones are estrogen and progesterone, whose main functions are the development and maintenance of female sexual characteristics, as well as participating in the development of the menstrual cycle, fertility, preparation of the reproductive system for the reception of sperm and gestation. The most important estrogen synthesized by the ovary is estradiol, while progesterone is the most important hormone of the gestagens or pregnancy hormones.

Sex hormone binding globulin (SHBG), produced by the liver, is a circulating steroid transport protein. It is produced by hepatocytes and binds to biologically active androgens and estrogens, thereby regulating their plasma levels and bioavailability.

In addition to controlling plasma distribution, intrinsic metabolic clearance (the ability of hepatocytes to eliminate a substance without influence from the bloodstream) and bioavailability, it also controls the metabolic intrinsic clearance (the ability of hepatocytes to eliminate a substance without influence from the bloodstream) and bioavailability.neo) and the bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts further effects on the action of androgens and estrogens.

Since the liver is the central metabolic organ in which it is produced, certain metabolic diseases cause changes in serum SHBG levels. SHBG levels can also vary due to endocrine disorders, thus SHBG stands as one of the mediators between various endocrine tissues and definitely contributes its own pathophysiological role in diseases such as: obesity, metabolic syndrome, polycystic ovary syndrome, osteoporosis, breast and prostate cancer.

It is estimated that approximately 50% of the variation in SHBG concentrations in the bloodstream is inherited from the parents, suggesting that SHBG levels are under significant genetic control.

Changes in sex hormone levels such as SHBG or testosterone are subject to various environmental factors such as age as well as genetic factors. One of the latest GWAS studies to date has used nearly 370,000 participants of European ancestry to identify 553 markers associated with SHBG levels. Some of the most significant markers found to be associated with SHBG levels in the study pertain to genes such as SERPINA1, which produces the protein aldase-1-antitrypsin, and other genes such as OCEL1 and SOX15.

Number of observed variants

13.5 million variants

Number of loci analyzed in the study

553 loci


Ruth K.S., Day F.R., et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nature Medicine, 10 Feb 2020, 26(2):252-258

Hammond G.L. Diverse Roles for Sex Hormone-Binding Globulin in Reproduction. Biol Reprod. 2011 Sep; 85(3): 431–441.

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