PLASMINOGEN-ACTIVATOR INHIBITOR-1 IS EXPRESSED IN CULTURED RAT SERTOLI CELLS

Sertoli cells secrete plasminogen activators (PAs) on both sides of th e blood-testis barrier, i.e., in the basal and apical compartments of the seminiferous tubules, whereas peritubular cells secrete plasminoge n activator inhibitor-1 (PAI-1), a fast-acting and specific PA inhibit or. While it is likely that PAI-1 produced by peritubular cells counte racts the basal secretion of PA, the nature of the PA inhibitor acting in the apical compartment remains to be demonstrated. In the present study, we showed that Sertoli cells recovered from 20-day-old rats and cultured contained a transcript of 3-3.2 kilobases, which hybridized specifically to a PAI-1 cDNA probe (Northern blot). We verified that t he observed PAI-1 transcript could not result solely from the peritubu lar cells (weakly contaminating the Sertoli cell cultures), by compari ng PAI-1 mRNA levels of Sertoli and peritubular cells recovered from 2 0-day-old rats and cultured. We also demonstrated that cultured Sertol i cells secreted a protein that complexed with tissue-type PA (zymogra phy), indicating that it was biologically active. This protein comigra ted with purified PAI-1 as a doublet of 46 and 49 kDa (Western blot). The trophic hormone FSH decreased PAI-1 messenger RNA as well as immun oreactive PAI-1 protein (probably via the cAMP protein kinase A pathwa y), whereas transforming growth factor beta 1 and basic fibroblast gro wth factor (in a nanomolar concentration) increased both of these. The se observations support the hypothesis that PAI-1 is expressed by Sert oli cells and is under a complex hormonal (FSH) and paracrine and/or a utocrine control exerted at least by basic fibroblast growth factor an d transforming growth factor beta 1.