MT1-MMP in rat testicular development and the control of Sertoli cell proMMP-2 activation

Metalloproteases (MMPs) are likely to be involved in the restructuring even ts occurring in the testis throughout development. We here demonstrate that membrane-type 1 (MT1)-MMP, a physiological activator of proMMP-2 under TIM P-2 control, is present within the testis together with MMP-2 and TIMP-2. I n the prepubertal testis MT1-MMP immunoreactivity was uniformly distributed , whereas in the adult it was confined to the apical compartment of the tub ules, where meiosis and spermiogenesis occur. We further showed that the tw o cell lineages (somatic and germinal) expressed MT1-MMP and TIMP-2, wherea s MMP-2 was of somatic origin. To get a better picture into proMMP-2 activa tion, use was made of a model of cultured Sertoli cells treated with FSH or co-cultured with germ cells to mimic an immature or a mature developmental period, respectively. We found that follicle-stimulating hormone enhanced the expression of MMP-2 and TIMP-2 but not of MT1-MMP, and promoted the act ivation of proMMP-2. In co-cultures, a tremendous elevation and activation of MMP-2 was observed, which might relate to the processed MT1-MMP form sol ely detected in germ cells. That MMP-2 synthesis and activation are under l ocal (germ cells) and hormonal (follicle-stimulating hormone) regulation em phasizes the importance of MMPs in testicular physiology.