COORDINATED AND CELL-SPECIFIC REGULATION OF MEMBRANE TYPE MATRIX METALLOPROTEINASE 1 (MT1-MMP) AND ITS SUBSTRATE MATRIX METALLOPROTEINASE 2(MMP-2) BY PHYSIOLOGICAL SIGNALS DURING FOLLICULAR DEVELOPMENT AND OVULATION

In the ovary, extensive tissue remodeling is required during both foll icular development and the break down of the follicular wall at the ti me of ovulation. Extracellular proteases such as serine proteases and matrix metalloproteinases (MMPs) are thought to play pivotal roles in these processes. In this paper, we have used in situ hybridization to study the regulation and distribution of mRNA coding for MMP-2 (gelati nase A) and its cell surface activator membrane-type MMPI (MT1-MMP) du ring gonadotropin induced ovulation in the rat. In ovaries of untreate d immature (23 day old) rats, the levels of MT1-MMP and MMP-2 mRNA wer e low. MMP-2 mRNA was found in theca-interstitial cells while MT1-MMP mRNA was found in both granulosa and theca-interstitial cells and both messages were induced after stimulation with PMSG. After an ovulatory dose of hCG, the expression of MT1-MMP was dramatically down regulate d in the granulosa cell layers of large preovulatory follicles but the expression remained and appeared to be up regulated together with MMP -2 in the theca-interstitial cells surrounding the large preovulatory follicles. The expression kinetics and tissue distribution supports th e notion that MT1-MMP may have dual functions in the ovary. Initially MT1-MMP may act as a matrix degrading protease inside the follicle dur ing follicular development and later, just prior to ovulation, as an a ctivator of proMMP-2 in theca-interstitial cells surrounding preovulat ory follicles.