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Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Deficient Mice Display Reduced Serum Progesterone Levels during Corpus Luteum Development

Departments of Obstetrics & Gynecology and Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160

Address all correspondence and requests for reprints to: Warren B. Nothnick, Ph.D., Department of Obstetrics and Gynecology, University of Kansas School of Medicine, 3901 Rainbow Blvd., Kansas City, Kansas 66160. E-mail: wnothnic{at}kumc.edu

Abstract

TIMP-1 is a multifunctional protein that is abundantly expressed within the ovary during the period of early corpus luteum formation. TIMP-1 has been suggested to play a role in progesterone production, but reports are conflicting. To more thoroughly examine the role of TIMP-1 in steroidogenesis during early luteal development in vivo, immature wild-type and TIMP-1 null female mice were primed with gonadotropins. Mice were sacrificed at 0, 24, and 48 h post hCG administration and serum was collected for determination of estradiol (E₂) or progesterone (P₄) concentrations. In the 24 h hCG groups, ovulation was assessed by counting the number of shed ova. Serum P₄ concentrations were significantly lower in the TIMP-1 null mice, both at 24 and 48-h post hCG compared to wild-type counterparts. No differences were detected in the number of ovulations between genotypes at the 24 h time point. In both the 24 and 48 h post-hCG groups, null mice had significantly higher ovarian wet weights. Interestingly, ovarian MMP activity was greater in the null mice at 24 h post hCG but higher in the wild-type at 48 h post hCG administration. These observations suggests that expression of TIMP-1 during early luteal development may participate in regulation of progesterone production via its ability to regulate ovarian MMP activity.

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