Hormone regulated inflammation of the immature rat uterus in response to leukocyte infiltration and MMP activation

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Description: The immature rat uterus has been extensively used as an in vivo model to study the effects of estrogen on the organ. By removing the ovaries (ovariectomy; OVX), the primary source of estrogen, it is possible to exogenously control the level of estrogen circulating in the body to achieve a desired effect using a form of estrogen known as 17β estradiol (E 2 ). It has been shown that single, physiological dose of E 2 , 40 μg/kg, produces a biphasic growth pattern in the uterus. The first phase of this pattern peaks approximately 4 hr post-E 2 treatment and is characterized by hypertrophic growth in the uterus. This phase involves extensive tissue sloughing and remodeling, including degradation of the extra-cellular matrix through the action of Matrix Metalloproteinases (MMPs), which degrade the collagen in the extra-cellular matrix. The second phase, peaking around 24 hr post treatment, is characterized by hyperplastic growth and a reforming of the extra-cellular matrix. The early phase of this growth pattern is particularly interesting, because an inflammatory-like response is also observed. The aim of this study was to further examine this inflammatory-like response and how it relates to tissue remodeling. Previous studies have shown MMP-mediated tissue remodeling beings as early as one hr post treatment. In this study, I have shown this process can begin as early as 30 min post-E 2 treatment. I have also shown significant levels of three pro-inflammatory cytokines (TNF-α, IL-1a and MCP-1) are present during tissue remodeling. This suggests that MMP-mediated tissue remodeling occurs along with a significant change in TNF-α, IL-1a and MCP-1 levels. How these two processes are exactly related, however, remains unknown.
Language: English
Format: Degree Work