INHIBIN, ACTIVIN AND FOLLISTATIN BIND PREFERENTIALLY TO THE TRANSFORMED SPECIES OF ALPHA(2)-MACROGLOBULIN

alpha(2)-Macroglobulin (alpha(2)-M), a major serum glycoprotein, has b een implicated as a low-affinity binding protein for inhibin and activ in. In serum, alpha(2)-M exists as two major species, a native form th at 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 we re investigated for their ability to bind to the native or transformed species of purified human alpha(2)-M. Using native PAGE and size excl usion chromatography, radiolabelled inhibin, activin and follistatin b ound to the transformed alpha(2)-M. inhibin and follistatin did not bi nd significantly to native alpha(2)-M, whereas activin was able to bin d to the native species but with a lower capacity compared with that t o transformed alpha(2)-M. Under reducing conditions, binding of these hormones to alpha(2)-M was abolished. These findings implicate g-M as a mechanism whereby inhibin, activin and follistatin may be removed fr om the circulation through alpha(2)-M receptors, but also whereby acti vin can be maintained in the circulation through its ability to bind t o native alpha(2)-M.