When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).

Because SHBG binds to testosterone (T) and dihydrotestosterone (DHT), these hormones are made less lipophilic and become concentrated within the luminal fluid of the seminiferous tubules.

The higher levels of these hormones enable spermatogenesis in the seminiferous tubules and sperm maturation in the epididymis.

SHBG’s production is regulated under the influence of FSH[6] 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.

[9] Low SHBG levels in women have been associated with hyperandrogenism and endometrial cancer due to heightened exposure to androgens and estrogens, respectively.

[9] The high SHBG levels during pregnancy may serve to protect the mother from exposure to fetal androgens that escape metabolism by the placenta.

[9] A case report of severe hyperandrogenism in a pregnant woman due to a rare instance of genetic SHBG deficiency illustrates this.

[19] (TAAAA)(n) is five base pairs that repeats a variable number of times on the opposite DNA strand.

[20] The mechanism of activating the promoter for SHBG in the liver involves hepatocyte nuclear factor 4 alpha (HNF4A) binding to a DR1-like cis-element which then stimulates production.

[7] Sex hormone-binding globulin is homodimeric, meaning it has two identical peptide chains making up its structure.

The amino acid sequence is the same as for androgen-binding protein produced in testes, but with different oligosaccharides attached.

The common downstream mechanism for all of these, including the effect of thyroid hormones,[22] was downregulation of hepatocyte nuclear factor 4 (HNF4).

[33] SHBG levels increase with estrogenic states (oral contraceptives), pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs.

[35] In utero, the human fetus has a low level of SHBG, allowing increased activity of sex hormones.

[37] SHBG is a useful correlate and indirect marker of estrogen-induced procoagulation and by extension thrombosis, for instance with birth control pills.

[38][39][40] Oral contraceptives containing ethinylestradiol can increase SHBG levels 2- to 4-fold and decrease free testosterone concentrations by 40 to 80% in women.

[41][9] Some oral contraceptives, namely those containing high doses of ethinylestradiol (which have been discontinued and are no longer marketed), can increase SHBG levels as much as 5- to 10-fold.