title: Inhibin, activin and follistatin bind preferentially to the transformed species of alpha 2-macroglobulin.
abstract: alpha 2-Macroglobulin (alpha 2-M), a major serum glycoprotein, has been implicated as a low-affinity binding protein for inhibin and activin. In serum, alpha 2-M exists as two major species, a native form that is abundant and stable, and a transformed ('fast') species that is rapidly cleared from the circulation via alpha 2-M receptors. In this study inhibin, activin and their major binding protein follistatin were investigated for their ability to bind to the native or transformed species of purified human alpha 2-M. Using native PAGE and size exclusion chromatography, radiolabelled inhibin, activin and follistatin bound to the transformed alpha 2-M. Inhibin and follistatin did not bind significantly to native alpha 2-M, whereas activin was able to bind to the native species but with a lower capacity compared with that to transformed alpha 2-M. Under reducing conditions, binding of these hormones to alpha 2-M was abolished. These findings implicate alpha 2-M as a mechanism whereby inhibin, activin and follistatin may be removed from the circulation through alpha 2-M receptors, but also whereby activin can be maintained in the circulation through its ability to bind to native alpha 2-M.
authors.affiliation: Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Phillips
authors.forename: J R
authors.initials: JR
authors.lastname: McFarlane
authors.forename: M T
authors.initials: MT
authors.lastname: Hearn
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
mesh_terms: D028341:Activins; D001667:Binding, Competitive; D002845:Chromatography; D004591:Electrophoresis, Polyacrylamide Gel; D038681:Follistatin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D038681:Follistatin; D006023:Glycoproteins; D000511:alpha-Macroglobulins; D028341:Activins; D007265:Inhibins