Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome

Quezada, Susana; Avellaira, Carla; Johnson, Marı́a Cecilia; Gabler, Fernando; Fuentes, Ariel; Vega, Margarita

doi:10.1016/j.fertnstert.2005.09.053

Cited by 104 publications

(88 citation statements)

References 38 publications

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“…ovary, in addition to the hyperinsulinemia present in a high percentage of PCOS women, may affect the function of several tissues (32), including the endometrium. Previously, our group has shown changes in the expression of certain molecules related to tissue homeostasis, intracellular steroid bioavailability (17,33,31) and uterine receptivity (18) in PCOS endometrial tissue. In the present study we assessed the endometrial expression of some proteins involved in the pathway of insulin, the PI3K-Akt route, which is known to participate in glucose uptake mediated by insulin in the cells (21,34).…”

Section: Discussionmentioning

confidence: 99%

“…This tissue has a cyclic behavior regulated by ovarian steroids, and in PCOS endometrium we have observed overexpression of steroid receptors and coactivators (13,14) and deregulation of endometrial homeostasis (15)(16)(17). In addition, endometria from PCOS women exhibit alterations in the levels of molecules associated with uterine receptivity (18). However, little information is available about the regulatory role exerted by insulin in the endometria from control and PCOS women.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the Expression of Insulin Signaling Pathway Molecules in Endometria from Polycystic Ovary Syndrome Women with or without Hyperinsulinemia

Fornes

Ormazábal

Rosas

et al. 2009

Mol Med

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Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder associated with insulin resistance and compensatory hyperinsulinemia. Scarce information is available on the expression of molecules involved in the insulin pathway in endometria from women with PCOS. Therefore, we examined the protein levels of insulin-signaling molecules, like insulin receptor, insulin-receptor substrate (IRS)-1, pIRS-1Y612, Akt, AS160, pAS160T642 and GLUT4 in endometria from PCOS women with or without hyperinsulinemia. Protein levels were assessed by Western blot and immunohistochemistry in 21 proliferative-phase endometria from control women (CE = 7), normoinssulinemic PCOS women (PCOSE-NI = 7) and hyperinsulinemic PCOS women (PCOSE-HI = 7). The data show no differences in the expression of insulin receptor between all groups as assessed by Western blot; however, IRS-1 and pIRS-1Y612 were lower in PCOSE-HI than controls and PCOSE-NI (P < 0.05). AS160 was detected in all analyzed tissues with similar expression levels between groups. Importantly, PCOSE-HI exhibited lower levels of pAS160T642 (P < 0.05) and of GLUT4 (P < 0.05) compared with CE. The immunohistochemistry for insulin receptor, IRS-1, Akt, AS160 and GLUT4 showed epithelial and stromal localization; IRS-1 staining was lower in PCOSE-HI (P < 0.05). In conclusion, human endometrium has the machinery for glucose uptake mediated by insulin. The diminished expression of GLUT4, as well as the lower level of pIRS-1Y612 and pAS160T642 exhibited by PCOSE-HI, suggests a disruption in the translocation of vesicles with GLUT4 to the cell surface in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in the Expression of Insulin Signaling Pathway Molecules in Endometria from Polycystic Ovary Syndrome Women with or without Hyperinsulinemia

Fornes

Ormazábal

Rosas

et al. 2009

Mol Med

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“…With the enormous potential of coregulators as master regulators, their deregulation is likely to provide the cancer cells an advantage in proliferation, survival, and metastasis (15,16). A few recent studies examined the status of NR coreguators in ovarian cancer cells and tumors, and found deregulation of few coregulators including AIB1, SRA, and ARA70 (17)(18)(19). Collectively, these emerging findings suggest that several NR-coregulatory proteins have potential to be differentially expressed in malignant tumors, and that their functions may be altered, leading to tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Role of PELP1/MNAR Signaling in Ovarian Tumorigenesis

et al. 2008

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Emerging evidence suggests that nuclear receptor (NR) coregulators have potential to act as master genes and their deregulation can promote oncogenesis. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is a novel NR coregulator. Its expression is deregulated in hormonedriven cancers. However, the role of PELP1/MNAR in ovarian cancer progression remains unknown. Analysis of serial analysis of gene expression data suggested deregulation of PELP1/MNAR expression in ovarian tumors. Western analysis of PELP1/MNAR in normal and serous ovarian tumor tissues showed 3-to 4-fold higher PELP1/MNAR expression in serous tumors compared with normal ovarian tissues. To examine the significance of PELP1/MNAR in ovarian cancer progression, we have generated model cells that overexpress PELP1/MNAR and ovarian cancer cells in which PELP1/MNAR expression is down-regulated by stable expression of PELP1/MNAR-specific shRNA. Down-regulation of PELP1/MNAR in cancerous ovarian model cells (OVCAR3) resulted in reduced proliferation, affected the magnitude of c-Src and protein kinase B (AKT) signaling, and reduced tumorigenic potential of ovarian cancer cells in a nude mouse model. PELP1/MNAR overexpression in nontumorigenic immortalized surface epithelial cells (IOSE cells) promoted constitutive activation of c-Src and AKT signaling pathways and promoted anchorageindependent growth. Immunohistochemical studies using human ovarian cancer tissue arrays (n = 123) showed that PELP1/MNAR is 2-to 3-fold overexpressed in 60% of ovarian tumors, and PELP1/MNAR deregulation occurs in all different types of ovarian cancer. Collectively, these results suggest that PELP1/MNAR signaling plays a role in ovarian cancer cell proliferation and survival, and that its expression is deregulated in ovarian carcinomas. [Cancer Res 2008;68(12):4902-9]

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“…Similarly, women with PCOS have been reported to have reduced expression of insulin signaling molecules (such as insulin-receptor substrates-1, and PPAR gamma) as compared to control women (24,25). Lack of endometrial shedding in the preceding cycle may influence expression of factors considered to be important to endometrial receptivity, such as integrins, osteopontin, leukemia inhibitory factor, glycodelin, TNF-α, TGF-β, and VEGF (20,(26)(27)(28)(29)(30)(31). Importantly, these observations are consistent with evaluation of androgen receptor expression in pig endometrium during early pregnancy, which indicated a role for the androgen receptor in defining the window of implantation and early pregnancy endometrium, thereby affecting the potential for early pregnancy loss (32).…”

Section: Discussionmentioning

confidence: 99%

Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome

Diamond¹,

Krüger²,

Santoro³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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Objective-To estimate whether progestin-induced endometrial shedding, prior to ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS).Methods-A secondary analysis of the data from 626 women with PCOS from the National Institutes of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed).Results-While ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live birth per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; p<0.001). The difference was more marked when rate was calculated per ovulation (live birth per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; p < .001).Conclusion-Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared to anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin prior to ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS.

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Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome

Cited by 104 publications

References 38 publications

Changes in the Expression of Insulin Signaling Pathway Molecules in Endometria from Polycystic Ovary Syndrome Women with or without Hyperinsulinemia

Changes in the Expression of Insulin Signaling Pathway Molecules in Endometria from Polycystic Ovary Syndrome Women with or without Hyperinsulinemia

Role of PELP1/MNAR Signaling in Ovarian Tumorigenesis

Endometrial Shedding Effect on Conception and Live Birth in Women With Polycystic Ovary Syndrome

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