Antiprogesterone (RU486) effects on metalloproteinase inhibitor activity in human and rat granulosa cells

A. Morgan, S. C. Keeble, S. N. London, K. N. Muse, T. E. Curry

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Objective: To determine if granulosa cells are a source of metalloproteinase inhibitor activity and whether P regulates this activity. Design: Inhibitor activity was measured in media from human and rat granulosa cells cultured with the antiprogesterone mifepristone (RU486). Human granulosa cells were obtained at the time of oocyte retrieval from gonadotropin-stimulated patients after hCG administration. Rat cells were collected from gonadotropin-primed animals before the LH surge. Human and rat cells were cultured for 24 hours in the absence or presence of LH (100 ng/mL or 3.3 nmol/L) and/or RU486 (5 μM or 50 μM). Inhibitor activity and P were measured in the media. Setting: Reproductive Endocrinology Laboratories, University of Kentucky. Results: Media from human granulosa cells contained metalloproteinase inhibitor activity and the addition of LH did not change this activity. RU486 at 50 μM decreased inhibitor activity in cells cultured in the absence or presence of LH (0.59 ± 0.12- and 0.24 ± 0.18-fold change, respectively, versus control cultures; mean ± SEM). In rat granulosa cells, inhibitor activity increased with LH treatment (1.97 ± 0.12-fold change). RU486 decreased the activity present in cells cultured in the presence of LH. Progesterone production was stimulated by LH in both human and rat granulosa cells (3.71 ± 0.90- and 7.18 ± 0.24-fold change, respectively). In the human cells, RU486 inhibited P production whereas RU486 stimulated P production in the rat cells. Conclusions: These findings demonstrate for the first time that human granulosa cells are a source of metalloproteinase inhibitor activity. The decrease in granulosa cell-derived inhibitor activity by RU486 suggests that P stimulates inhibitor activity. Thus, P may regulate proteolysis associated with follicular rupture via its ability to stimulate granulosa cell production of metalloproteinase inhibitors. Differences in P production between the human and rat cells may be due to differences in hormonal stimulation regimens (i.e., hCG exposure).

Original languageEnglish
Pages (from-to)949-955
Number of pages7
JournalFertility and Sterility
Issue number5
StatePublished - 1994

Bibliographical note

Funding Information:
Received April 23, 1993; revised and accepted December 10, 1993. * Supported by National Institutes of Health Grant HD23195, Bethesda, Maryland. t Presented in part at the 40th Annual Meeting of the Society for Gynecologic Investigation, Toronto, Canada, April 1 to 4, 1993. :j: Reprint requests: Thomas E. Curry, Jr., Ph.D., Department of Obstetrics and Gynecology, University of Kentucky Medical Center, SOO Rose Street, Lexington, Kentucky 40536-0084 (FAX: 606-258-1931).


  • Ovary
  • RU486
  • collagenase
  • granulosa cell
  • metalloproteinase inhibitor
  • ovulation
  • progesterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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