Reproductive Biology and Endocrinology (Nov 2009)

Regulated expression of matrix metalloproteinases, inflammatory mediators, and endometrial matrix remodeling by 17beta-estradiol in the immature rat uterus

  • Caruso Joseph A,
  • Olenchock Benjamin A,
  • Cavalcanto Todd D,
  • Trivedi Shreya P,
  • Peano Bryan J,
  • Russo Louise A,
  • Smolock Amanda R,
  • Vishnevsky Oleg,
  • Gardner Russell M

DOI
https://doi.org/10.1186/1477-7827-7-124
Journal volume & issue
Vol. 7, no. 1
p. 124

Abstract

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Abstract Background Administration of a single physiological dose of 17beta-estradiol (E2:40 microg/kg) to the ovariectomized immature rat rapidly induces uterine growth and remodeling. The response is characterized by changes in endometrial stromal architecture during an inflammatory-like response that likely involves activated matrix-metalloproteinases (MMPs). While estrogen is known as an inducer of endometrial growth, its role in specific expression of MMP family members in vivo is poorly characterized. E2-induced changes in MMP-2, -3, -7, and -9 mRNA and protein expression were analyzed to survey regulation along an extended time course 0-72 hours post-treatment. Because E2 effects inflammatory-like changes that may alter MMP expression, we assessed changes in tissue levels of TNF-alpha and MCP-1, and we utilized dexamethasone (600 microg/kg) to better understand the role of inflammation on matrix remodeling. Methods Ovariectomized 21 day-old female Sprague-Dawley rats were administered E2 and uterine tissues were extracted and prepared for transmission electron microscopy (TEM), mRNA extraction and real-time RT-PCR, protein extraction and Western blot, or gelatin zymography. In inhibitor studies, pretreatment compounds were administered prior to E2 and tissues were harvested at 4 hours post-hormone challenge. Results Using a novel TEM method to quantitatively assess changes in stromal collagen density, we show that E2-induced matrix remodeling is rapid in onset ( Conclusion The data demonstrate that E2-regulated endometrial remodeling is rapid in onset (