REGULATION OF SERTOLI-CELL ALPHA-2-MACROGLOBULIN AND CLUSTERIN (SGP-2) SECRETION BY PERITUBULAR MYOID CELLS

Alpha2-macroglobulin and clusterin are two putative Sertoli cell secretory products; however, the regulator(s) modulating their secretion by Sertoli cells is not known. Recent studies from this laboratory have shown that the testicular alpha2-macroglobulin, unlike its liver homologue, is not an acute-phase reactant and its concentration is not affected by acute inflammation. We sought to determine whether FSH, testosterone, and other biomolecules would affect the secretion of alpha2-macroglobulin and clusterin by Sertoli cells as well as whether peritubular myoid cells would affect the secretion of these proteins by Sertoli cells. It was noted that Sertoli cells cultured in vitro secreted increasing amounts of alpha2-macroglobulin and clusterin as a function of time. FSH (50-1000 ng/ml) and testosterone (10(-11)-10(-5) m) had no apparent effect on the secretion of alpha2-macroglobulin and clusterin by Sertoli cells. Addition of interleukin-6 to Sertoli cell-enriched cultures, in doses known to stimulate alph2-macroglobulin secretion by hepatocytes, did not affect the alpha2-macroglobulin secretion. However, dexamethasone at 10(-7)-10(-5) M stimulated alpha2-macroglobulin secretion by Sertoli cells dose-dependently while the addition of interleukin-6 had no synergistic effect on dexamethasone-stimulated alpha2-macroglobulin secretion. These findings suggest that the synthesis and/or secretion of alpha2-macroglobulin by Sertoli cells is regulated by a mechanism distinct from that of the liver. Peritubular cells cultured alone did not produce any measurable amounts of either alpha2-macroglobulin or clusterin; however, co-cultures of pcritubular cells with Sertoli cells induced a significant increase in alpha2-macroglobulin and clusterin secretion by Sertoli cells. Addition of testosterone to the Sertoli cell-peritubular cell co-culture system did not affect the levels of alpha2-macroglobulin and clusterin. In summary, FSH and testosterone, at doses known to affect Sertoli cell function, did not affect the secretion of alpha2-macroglobulin and clusterin; however, peritubular cells modulate the secretion of both alpha2-macroglobulin and clusterin by Sertoli cells.