Regulation of Sertoli Cell α2-Macroglobulin and Clusterin (SGP-2) Secretion by Peritubular Myoid Cells1

α2-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 α2-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 α2-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 α2-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 α2-macroglobulin and clusterin by Sertoli cells. Addition of interleukin-6 to Sertoli cell-enriched cultures, in doses known to stimulate α2-macroglobulin secretion by hepatocytes, did not affect the α2-macroglobulin secretion. However, dexamethasone at 10−7–10−5 M stimulated α2-macroglobulin secretion by Sertoli cells dose-dependently while the addition of interleukin-6 had no synergistic effect on dexamethasone-stimulated α2-macroglobulin secretion. These findings suggest that the synthesis and/or secretion of α2-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 α2-macroglobulin or clusterin; however, co-cultures of peritubular cells with Sertoli cells induced a significant increase in α2-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 α2-macroglobulin and clusterin. In summary, FSH and testosterone, at doses known to affect Sertoli cell function, did not affect the secretion of α2-macroglobulin and clusterin; however, peritubular cells modulate the secretion of both α2-macroglobulin and clusterin by Sertoli cells.