Secretion and gene expression of metalloproteinases and gene expression oftheir inhibitors in porcine corpora lutea at different stages of the luteal phase

We hypothesize that spontaneous regression of corpora lutea (CL) involves s hort-lasting restructure of luteal tissue with an activation of matrix meta lloproteinases (MMPs) and their respective inhibitors (tissue inhibitors of metalloproteinase, TIMPs). This was tested by determining the gene express ion of MMP-1, MMP-2, and MMP-9 and respective TIMP-1 and TIMP-2 in luteal t issue from sows at the early, midluteal, and late luteal phase (Days 6-8, D ays 9-11, and Days 13-15 of estrous cycle). Gene expression of the three MM Ps was low in early, slightly higher in midluteal, and significantly elevat ed (P < 0.05) in regressing CL. An inverse pattern was found for gene expre ssion of TIMP-1 and TIMP-2. Under culture conditions, the release of MMPs w as determined from steroidogenic large luteal cells (LLC). LLC harvested fr om regressing CL released significantly (P < 0.05) more active MMPs than ce lls obtained from CL at the early luteal phase. As luteolysis can be induce d by prostaglandin F-2 alpha (PGF(2 alpha)) and tumor necrosis factor alpha (TNF), we studied their effects on LLC under culture conditions. Treatment of cells with PGF(2 alpha) or TNF (10(-7) M or 3 x 10(-9) M, respectively) induced a significantly higher release of MMPs, and gene expression was al so significantly stimulated in comparison to that in untreated LLC. The gen e expression of TIMPs remained unaffected by either treatment. It is conclu ded that at the beginning of luteolysis, MMPs are expressed and released in high amounts and that this is essential for the structural regression of t he CL.