Macrophage migration inhibitory factor (MIF) as a paracrine mediator in the interaction of testicular somatic cells

Originally the macrophage migration inhibitory factor (MIF) was described a s a classical T-cell cytokine. Recently, a much broader tissue distribution for MIF has been revealed. We demonstrated that MIF protein and mRNA are p resent in the Leydig cells of the normal adult rat testis. Addition of reco mbinant MIF to cultures of rat seminiferous tubules resulted in decreased s ecretion of inhibin, whereas follistatin and activin levels remained unchan ged, suggesting a paracrine role for MIF in Sertoli cell regulation. Furthe rmore, MIF showed unique compensatory production in the rat testis. Depleti on of.,the original MIF source, the Leydig cells, by,the specific toxin EDS prompted MIF expression by the previously negative Sertoli cells; Leydig c ell re-population of the interstitial tissue by precursor cells resulted in a switch back to production by Leydig cells. Therefore, testicular MIF app ears to be under very tight paracrine control. MIF has thus been identified as a new mediator in the cross-talk between Leydig cells and the somatic c ells of the seminiferous tubules of the rat testis.