Retracted Article : Gonadotropin releasing hormone analogue (GnRHa) alters the expression and activation of Smad in human endometrial epithelial and stromal cells

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.

The Novel Competing Endogenous Long Noncoding RNA SM2 Regulates Gonadotropin Secretion in the Hu Sheep Anterior Pituitary by Targeting the Oar-miR-16b/TGF-β/SMAD2 Signaling Pathway

“…To further determine whether the lncRNA SM2 directly regulates gonadotropin secretion, we used GnRH to stimulate pituitary cells. Recent reports indicated that GnRH analogue treatment activated SMAD3 and SMAD4 in human endometrial stromal cells [50].…”

Noncanonical functions of glucocorticoids: A novel role for glucocorticoids in performing multiple beneficial functions in endometrial stem cells

“…Increased levels of glucocorticoids in response to stressful challenges result in a diverse range of cellular functions in a variety of cells throughout the body [ 43 , 44 ], many of which can be associated with reproductive dysfunction by suppressing the hypothalamic-pituitary-gonadal (HPG) axis [ 6 , 45 ]. At the level of the hypothalamus, glucocorticoids, such as cortisol, suppress the production and secretion of gonadotropin-releasing hormone (GnRH) [ 46 , 47 ], which in turn decreases estrogen production and subsequently reduces uterine receptivity [ 48 , 49 ]. In this context, glucocorticoid regulation of uterine functions has historically been considered to have secondary (indirect) effects on the actions of estrogen and progesterone.…”

Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation

“…The centrosome scaffold proteins Cep152 and Cep192 together with Plk4 are required to organize microtubules despite the absence of centrioles not only in mouse embryos [90,91] but also during murine meiosis. [92,93] γ-TuRC, the key microtubule templating activity, remains essential for spindle formation in the absence or presence of centrosomes (Reviewed in: Ref. [49] ).…”