SERTOLI-CELL SYNTHESIZES AND SECRETES A PROTEASE INHIBITOR, ALPHA-2-MACROGLOBULIN

The mechanism by which the seminiferous epithelium limits the damaging effects of proteases that are released from degenerating late spermatids does not depend upon protease inhibitors in the systemic circulation since these proteins are excluded from the seminiferous tubule by the blood-testis barrier. The purpose of this study was to identify the major protease inhibitor of the testis and determine its cellular origin. Sertoli cells, the major epithelial component of the seminiferous epithelium, release a protease inhibitor, testicular α2-macroglobulin, in vitro. Immunoprecipitation using [35S] methionine and a monospecific polyclonal antibody prepared against purified testicular α2-macroglobulin establishes that this protein is actively synthesized and secreted by Sertoli cells. Measurements of immunoreactive protease inhibitors in tubular and rete testis fluids collected by micropuncture suggest that α2-macroglobulin rather than α1-antitrypsin is the major protease inhibitor in the seminiferous tubules in vivo. The ability of α2-macroglobulin to inactivate proteases and growth factors such as TGF-β by a common mechanism suggests that this protein may have a dual function in the testis. © 1990, American Chemical Society. All rights reserved.