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This Article Full Text Full Text (PDF) All Versions of this Article: 68/1/214    most recent biolreprod.102.005678v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Simpson, K. S. Articles by Curry, T. E. Search for Related Content PubMed PubMed Citation Articles by Simpson, K. S. Articles by Curry, T. E., Jr Agricola Articles by Simpson, K. S. Articles by Curry, T. E.

Localization and Expression of Tissue Inhibitor of Metalloproteinase-4 in the Immature Gonadotropin-Stimulated and Adult Rat Ovary¹

^a Department of Obstetrics and Gynecology, University of Kentucky, Lexington, Kentucky 40536-0298

The tissue inhibitors of metalloproteinases (TIMPs) are important regulators of the matrix metalloproteinases (MMPs), proteolytic enzymes essential for controlling the coordinated tissue remodeling that takes place in the ovary. In the present study, we characterized the ovarian expression pattern of TIMP-4. The localization of TIMP-4 mRNA was determined by in situ hybridization in adult cycling rats. TIMP-4 mRNA on the day of estrus was expressed in a punctate pattern in stroma and in corpora lutea (CL) from previous cycles but not in newly formed CL or follicles. At metestrus, TIMP-4 mRNA was present in certain CL from the current and previous cycles and continued to exhibit a punctate pattern of expression in the stroma. By diestrus, TIMP-4 mRNA was detected in the thecal layer surrounding follicles, and a relatively high level of expression was observed in a punctate pattern within new and previous CL and in the stroma. TIMP-4 mRNA was also observed in the thecal layer at proestrus, but the punctate pattern within CL and stroma was absent. To correlate the changes in cellular localization with changes in overall TIMP-4 levels, ovarian mRNA and protein levels were examined in adult cycling rats and in gonadotropin-stimulated immature rats. In cycling rats, there was no change in mRNA or protein levels across the cycle, although there was a trend towards higher levels during estrus (P = 0.08). In gonadotropin-treated rats, there was an increase in TIMP-4 mRNA 48 h after eCG administration with a corresponding doubling of TIMP-4 protein. Although TIMP-4 mRNA and protein tended to decline after hCG treatment, this trend was not significant (P = 0.08). These findings indicate that TIMP-4 could play an important role in regulating MMPs in a localized manner in follicles and CL throughout the cycle.

¹ This work was supported by the Lalor Foundation (C.M.K.) and grants to T.E.C. (NIH HD23195 and NCRR P20 RR15592).

² Correspondence: Thomas Curry, Jr., Department of Obstetrics and Gynecology, Chandler Medical Center, Room MS 331, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298. FAX: 859 323 1931; tecurry{at}uky.edu

³ Current address: Department of Animal Science, Iowa State University, 2356F Kildee Hall, Ames, IA 50011-3150