Estrogen receptor-alpha ER-alpha and defects in uterine receptivity in womenReport as inadecuate




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Reproductive Biology and Endocrinology

, 4:S9

First Online: 09 October 2006

Abstract

Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and-or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha ER alpha, being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor EGF. By competing against estrogen with various selective estrogen receptor modulators SERMs and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies.

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Author: Bruce A Lessey - Wilder A Palomino - KBC Apparao - Steven L Young - Ruth A Lininger

Source: https://link.springer.com/







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