Sex hormone-binding globulin

1LHW, 1D2S, 1F5F, 1KDK, 1KDM, 1LHN, 1LHO, 1LHU, 1LHV646220415ENSG00000129214ENSMUSG00000005202P04278P97497NM_001289114NM_001289115NM_001289116NM_011367NP_001276043NP_001276044NP_001276045NP_035497Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin. SHBG is found in all vertebrates apart from birds.1d2s: CRYSTAL STRUCTURE OF THE N-TERMINAL LAMININ G-LIKE DOMAIN OF SHBG IN COMPLEX WITH DIHYDROTESTOSTERONE1f5f: CRYSTAL STRUCTURE OF THE N-TERMINAL G-DOMAIN OF SHBG IN COMPLEX WITH ZINC1kdk: THE STRUCTURE OF THE N-TERMINAL LG DOMAIN OF SHBG IN CRYSTALS SOAKED WITH EDTA1kdm: THE CRYSTAL STRUCTURE OF THE HUMAN SEX HORMONE-BINDING GLOBULIN (TETRAGONAL CRYSTAL FORM)1lhn: CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 5ALPHA-ANDROSTANE-3BETA,17ALPHA-DIOL1lho: CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 5ALPHA-ANDROSTANE-3BETA,17BETA-DIOL1lhu: CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH ESTRADIOL1lhv: CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH NORGESTREL1lhw: CRYSTAL STRUCTURE OF THE N-TERMINAL LG-DOMAIN OF SHBG IN COMPLEX WITH 2-METHOXYESTRADIOL Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound by transcortin. SHBG is found in all vertebrates apart from birds. Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 2% is unbound, or 'free,' and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT) > testosterone > androstenediol > estradiol > estrone. DHT binds to SHBG with about 5 times the affinity of testosterone and about 20 times the affinity of estradiol. Dehydroepiandrosterone (DHEA) is weakly bound to SHBG, but dehydroepiandrosterone sulfate is not bound to SHBG. Androstenedione is not bound to SHBG either, and is instead bound solely to albumin. Estrone sulfate and estriol are also poorly bound by SHBG. Less than 1% of progesterone is bound to SHBG. 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 5- to 10-fold. The high SHBG levels during pregnancy may serve to protect the mother from exposure to fetal androgens that escape metabolism by the placenta. A case report of severe hyperandrogenism in a pregnant woman due to a rare instance of genetic SHBG deficiency illustrates this. SHBG is produced mostly by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. The gene for SHBG is called Shbg located on chromosome 17 on the short arm between the bands 17p12→p13. Overlapping on the complementary DNA strand is the gene for spermidine/spermine N1-acetyltransferase family member 2 (SAT2). Nearby are the genes for p53 and ATP1B2, and fragile X mental retardation, autosomal homolog 2 (FXR2) on the complementary strand. There are eight exons, of which exon 1 has three variations called 1L, 1T and 1N which are triggered by three promoters: PL, PT and PN respectively. SHBG comes with the 1L, 2, 3, 4, 5, 6, 7, and 8 exons connected together. A variation includes SHBG-T which is missing exon 7 but with exon 1T promoted by promoter PT on the opposite strand, which shared with that for SAT2.