Steroid receptors zinc fingers

Zinc is lost through the skin and kidneys (combined loss of -/day) , more zinc being lost when the body sweats more, as in hot climates and during strenuous exercise. Approximately half of all zinc eliminated from the body is lost through the shedding of epithelial cells in the gastro intestinal tract (- 3mg/day) and although a considerable amount is secreted through both biliary and intestinal secretions, most of the secretions are reabsorbed regulating the zinc balance. Starvation and muscle breakdown also increase zinc loss through the urine.

Sex hormone-binding globulin (SHBG) is thought to mainly function as a transporter and reservoir for the estradiol and testosterone sex hormones. However it has also been demonstrated that SHBG can bind to a cell surface receptor (SHBG-R). The SHBG-R has not been completely characterized. A subset of steroids are able to bind to the SHBG/SHBG-R complex resulting in an activation of adenylyl cyclase and synthesis of the cAMP second messenger. [19] Hence the SHBG/SHBG-R complex appears to act as a transmembrane steroid receptor that is capable of transmitting signals to the interior of cells.

Rapid, cell surface-initiated, pregenomic androgen actions have been described in various vertebrate cells, but the receptors mediating these actions remain unidentified. We report here the cloning and expression of a cDNA from Atlantic croaker (Micropogonias undulatus) ovaries encoding a 33-kDa, seven-transmembrane protein with binding and signaling characteristics of a membrane androgen receptor that is unrelated to any previously described steroid receptor. Instead, croaker membrane androgen receptor has 81-93% amino acid sequence identity with zinc transporter ZIP9 (SLC39A9) subfamily members, indicating it is a ZIP9 protein. Croaker ZIP9 is expressed in gonadal tissues and in brain and is up-regulated in the ovary by reproductive hormones. Croaker ZIP9 protein is localized to plasma membranes of croaker granulosa cells and human breast cancer (SKBR-3) cells stably transfected with ZIP9. Recombinant croaker ZIP9 has a high affinity (dissociation constant, Kd, nM), limited capacity (maximal binding capacity nM/mg protein), displaceable, single binding site-specific for androgens, characteristic of steroid receptors. Testosterone activates a stimulatory G protein coupled to ZIP9, resulting in increased cAMP production. Testosterone promotes serum starvation-induced cell death and apoptosis in transfected cells and in croaker ovarian follicle cells that is associated with rapid increases in intracellular free zinc concentrations, suggesting an involvement of zinc in this nonclassical androgen action to promote apoptosis. These responses to testosterone are abrogated by treatment with ZIP9 small interfering RNA. The results provide the first evidence that zinc transporter proteins can function as specific steroid membrane receptors and indicate a previously unrecognized signaling pathway mediated by steroid receptors involving alterations in intracellular zinc.

Steroid receptors zinc fingers

steroid receptors zinc fingers


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