Retracted Article : Gonadotropin releasing hormone analogue (GnRHa) alters the expression and activation of Smad in huma
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BioMed Central
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Gonadotropin releasing hormone analogue (GnRHa) alters the expression and activation of Smad in human endometrial epithelial and stromal cells Xiaoping Luo1, Jingxia Xu1,2 and Nasser Chegini*1 Address: 1Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida, USA and 2Present address: The Jackson Laboratory, Bar Harbor, Main, USA Email: Xiaoping Luo - [email protected]; Jingxia Xu - [email protected]; Nasser Chegini* - [email protected] * Corresponding author
Published: 16 December 2003 Reproductive Biology and Endocrinology 2003, 1:125
Received: 21 August 2003 Accepted: 16 December 2003
This article is available from: http://www.rbej.com/content/1/1/125 © 2003 Luo et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract Gonadotropin releasing hormone analogues (GnRHa) are often used to regress endometriosis implants and prevent premature luteinizing hormone surges in women undergoing controlled ovarian stimulation. In addition to GnRH central action, the expression of GnRH and receptors in the endometrium implies an autocrine/paracrine role for GnRH and an additional site of action for GnRHa. To further examine the direct action of GnRH (Leuprolide acetate) in the endometrium, we determined the effect of GnRH on endometrial stromal (ESC) and endometrial surface epithelial (HES) cells expression and activation of Smads (Smad3, -4 and -7), intracellular signals activated by transforming growth factor beta (TGF-beta), a key cytokine expressed in the endometrium. The results show that GnRH (0.1 microM) increased the expression of inhibitory Smad7 mRNA in HES with a limited effect on ESC, while moderately increasing the common Smad4 and Smad7 protein levels in these cells (P < 0.05). GnRH in a dose- (0.01 to 10 microM) and time(5 to 30 min) dependent manner decreased the rate of Smad3 activation (phospho-Smad3, pSmad3), and altered Smad3 cellular distribution in both cell types. Pretreatment with Antide (GnRH antagonist) resulted in further suppression of Smad3 induced by GnRH, with Antide inhibition of pSmad3 in ESC. Furthermore, co-treatment of the cells with GnRH + TGF-beta, or pretreatment with TGF-beta type II receptor antisense to block TGF-beta autocrine/paracrine action, in part inhibited TGF-beta activated Smad3. In conclusion, the results indicate that GnRH acts directly on the endometrial cells altering the expression and activation of Smads, a mechanism that could lead to interruption of TGF-beta receptor signaling mediated through this pathway in the endometrium.
Introduction Excess production of ovarian steroids, as well as overexpression of their receptors, is believed to serve as an underlying molecular mechanism that promotes uterine abnormalities such as endometriosis, leiomyoma and endometrial cancer. Gonadotropin releasing hormo
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