Expression of matrix metalloproteinases and their tissue inhibitor messenger ribonucleic acids in macaque periovulatory granulosa cells: time course and steroid regulation.

Progesterone appears essential for ovulation and luteinization of the primate follicle, but specific gene targets of progesterone action remain elusive. Limited evidence supports a role for progesterone in the induction of collagenolytic activity in the periovulatory follicle of primate and nonprimate species. This study was designed to elucidate the pattern of expression and progesterone regulation of mRNAs for the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in macaque granulosa cells during controlled ovarian stimulation cycles before (0 h) and after (up to 36 h) administration of an ovulatory hCG bolus. Levels of mRNAs for interstitial collagenase, gelatinase A, matrilysin, TIMP-1 and TIMP-2 increased (p < 0.05) within 12 h of hCG, while gelatinase B mRNA increased later, by 36 h after hCG. Administration of a 3beta-hydroxysteroid dehydrogenase inhibitor (Trilostane [TRL]) during hCG treatment decreased (p < 0.05) mRNA levels for interstitial collagenase, gelatinase B, matrilysin, TIMP-1, and TIMP-2. Progestin (R5020) replacement during hCG+TRL treatment returned interstitial collagenase and TIMP-1 mRNAs to control levels. These data suggest that one action of progesterone, and possibly other steroids, in the cascade of events leading to ovulation and luteinization of the primate follicle is to regulate the expression of specific ovarian proteases and protease inhibitors.