Follistatins and alpha 2-macroglobulin are soluble binding proteins for inhibin and activin.
Inhibin is a 32-kD dimeric glycoprotein consisting of an alpha subunit and one of two beta subunits (beta A or beta B), which was isolated and cloned on the basis of its ability to inhibit FSH release from the pituitary. Activin results from the combination of two inhibins. Activins can cause stimulation of FSH release from pituitary cells both in vitro and in vivo, and in addition are involved in embryogenesis, erythropoiesis, and reproductive function. The inhibin-related peptides, and their receptors, are present in the testis and ovary from early gestation through adulthood. An additional level of control of the activity of growth factors is afforded by specific binding which may regulate protein turnover, localization and bioactivity. To date, two distinct binding proteins for inhibin and activin have been identified, both of which are expressed in the testes and other tissues and are present in the circulation. In serum, inhibin is primarily found associated with alpha 2-macroglobulin (alpha 2M), a high-capacity, low-affinity binding protein which binds many cytokines and growth factors. Binding to alpha 2M does not appear to alter immuno- or bioactivity of inhibin or activin. The second binding protein, follistatin, is produced in many of the same tissues which produce the activin and inhibin. This molecule may function primarily as a regulator of activin bioavailability and bioactivity. The affinity of follistatin for activin (< 0.1 nM) is similar to that of the high-affinity activin receptors. Thus, dynamic changes in the relative levels of the amount of any of these components could act to modulate activin and inhibin bioavailability in both a developmentally and tissue-restricted pattern in the testes and ovary.
Mather
J P
JP
Genentech, Inc., South San Francisco, CA 94080 USA.
D028341:Activins; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D038681:Follistatin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism*; D012995:Solubility; D000511:alpha-Macroglobulins / Q000378:metabolism*
D002352:Carrier Proteins; D038681:Follistatin; D006023:Glycoproteins; D000511:alpha-Macroglobulins; D028341:Activins; D007265:Inhibins