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Publication : Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice.

First Author  Nothnick WB Year  2004
Journal  Biol Reprod Volume  70
Issue  2 Pages  500-8
PubMed ID  14568914 Mgi Jnum  J:96726
Mgi Id  MGI:3531353 Doi  10.1095/biolreprod.103.020834
Citation  Nothnick WB, et al. (2004) Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice. Biol Reprod 70(2):500-8
abstractText  Tissue inhibitors of metalloproteinases (TIMPs) are expressed within the uteri of virtually all species where they are postulated to control extracellular matrix turnover, cellular apoptosis, and proliferation. The objective of the current study was to examine the steroidal regulation of uterine TIMP expression and to determine the potential role of the TIMP-1 gene product in this regulation. To accomplish these goals, ovariectomized female TIMP-1 wild-type and null mice were treated with estradiol, progesterone, or estradiol and progesterone and killed at various times after steroid administration. Estradiol induced a significant reduction in uterine TIMP-3 expression in wild-type mice at 8 and 24 h post-steroid administration, but the ability of this steroid to decrease TIMP-3 expression was impaired in the uteri of TIMP-1 null mice. Further, estrogen-induced uterine wet-weight gain/edema was enhanced in the TIMP-1 null mice, and the antiestrogen compound ICI 182780 or progesterone could only partially block this estrogenic effect. It is concluded from this study that steroidal modulation of uterine TIMP-3 expression and regulation of wet-weight gain/edema are altered in TIMP-1 null mice. These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema.
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