Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women.

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Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA

Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women.

Reprod Biol Endocrinol. 2006;4 Suppl 1:S9.

PubMed ID

17118173 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Allylestrenol	Estrogen receptor alpha	Protein	Humans	Unknown	Agonist	Details
Medroxyprogesterone acetate	Estrogen receptor alpha	Protein	Humans	Yes	Agonist	Details
Progesterone	Estrogen receptor alpha	Protein	Humans	Unknown	Agonist Inhibitor Downregulator	Details