Sex hormone-binding globulin: anatomy and physiology of a new regulatory system.
Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds a number of circulating steroid hormones (testosterone, dihydrotestosterone and estradiol) with high affinity, thus regulating their free concentration in plasma. In addition to binding steroids, SHBG itself binds to receptor sites on plasma membranes with somewhat unusual kinetics. Both the off and on rates are quite slow. The steroid-binding and membrane-binding functions are intertwined in what is clearly an allosteric relationship. Occupation of SHBG's steroid-binding site by a steroid inhibits its ability to bind to its membrane receptor-binding site. This inhibition is not related to a steroid's biological activity. Metabolites of steroids without biological activity, e.g. 2-methoxyestradiol, actively inhibit SHBG's interaction with its membrane receptor. However, if unliganded SHBG is allowed to bind to its receptor on intact cells, and an appropriate steroid hormone then is introduced, adenylate cyclase is activated and intracellular cAMP increases. This function is specific for steroids with biological activity, 2-methoxyestradiol has no activity in this arena. These observations demonstrate a potentially important role for SHBG as a regulator of cell function. They also demonstrate an additional mode of action of steroid hormones, one that does not require that the steroid interact with a steroid receptor.
Rosner
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W
Department of Medicine, St. Luke's/Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, NY 10019.
Hryb
D J
DJ
Khan
M S
MS
Nakhla
A M
AM
Romas
N A
NA
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D011467:Prostate / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D012738:Sex Hormone-Binding Globulin / Q000502:physiology*; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008024:Ligands; D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; C063572:sex hormone-binding globulin receptor; D000242:Cyclic AMP