Characterization of GAB1 Expression Over the Menstrual Cycle in Women With and Without Polycystic Ovarian Syndrome Provides a New Insight Into Its Pathophysiology

Roemer, Karen; Young, Steven L.; Savaris, Ricardo Francalacci

doi:10.1210/jc.2014-2128

Cited by 5 publications

(8 citation statements)

References 22 publications

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“…PPIA was chosen after a validation of 12 housekeeping genes in endometrium as described before. 32 Real-time PCR employed Brilliant II QPCR Master Mix (Stratagene) in a total reaction volume of 20 µL and was performed on a Stratagene MX3000P machine (Stratagene, La Jolla, CA) using 40 two-step cycles (95°C for 25 seconds, followed by 60°C for 1 minute). The RT-PCR data were analyzed using the 2 −ΔCt method, as described.…”

Section: Methodsmentioning

confidence: 99%

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis

et al. 2016

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The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance.

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Section: Methodsmentioning

confidence: 99%

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis

et al. 2016

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“…The mechanism underlying the effect of sex hormones on TRPC gene expression may involve the TNF-α and NF-κB pathways. The promoter region of TRPC1 contains an NF-κB binding site ENREF_40 [37][38][39][40] and it is recognized that estradiol, progesterone and FSH can all act through the this pathway [28,41]. Binding of NF-κB to DNA is likely to result in transcription of NF-κB-linked proteins such as TRPC1.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of transient receptor potential channels in the female bovine reproductive tract

et al. 2016

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The epithelium lining the oviduct is critical for early reproductive events, many of which are mediated via intracellular calcium ions. Despite this, little is known about the regulation of calcium homeostasis in the oviductal epithelium. Epithelial transient receptor potential channels (TRPCs) modulate calcium flux in other tissues, and their expression and functional regulation have therefore been examined using the bovine oviduct as a model for the human. The effects of FSH, LH, 17β-estradiol, and progesterone on TRPCs expression and intracellular calcium flux were determined. Transient receptor potential channels 1, 2, 3, 4, and 6 were expressed in the bovine reproductive tract, and their gene expression varied throughout the estrous cycle. In more detailed studies undertaken on TRPC1 and 6, we show that protein expression varied through the estrus cycle; specifically, 17β-estradiol, FSH, and LH individually and in combination upregulated TRPC1 and 6 expression in cultured bovine oviduct epithelial cells although progesterone antagonized these effects. Functional studies showed changes in calcium mobilization in bovine oviduct epithelial cells were dependent on TRPCs. In conclusion, TRPC1, 2, 3, 4, and 6 are present in the epithelium lining the bovine oviduct, and TRPC1 and 6 vary through the estrous cycle suggesting an important role in early reproductive function.

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“…Growth factor receptor-bound protein-2 (GRB2)-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, has been shown to be downregulated in the endometrium of women with PCOS [11] during menstrual cycle. This defect in insulin signaling due to GRB2-associated binding protein 1 downregulation might contribute to disturbed glucose metabolism in PCOS.…”

Section: Genetic Background Of Polycystic Ovary Syndromementioning

confidence: 99%

Genetics of insulin resistance in polycystic ovary syndrome

Obermayer–Pietsch

Trummer²,

Schwetz³

et al. 2015

Current Opinion in Clinical Nutrition and Metabolic Care

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Characterization of GAB1 Expression Over the Menstrual Cycle in Women With and Without Polycystic Ovarian Syndrome Provides a New Insight Into Its Pathophysiology

Abstract: GAB1 mRNA expression is positively modulated by E2. Endometrial GAB1 protein and mRNA expression are reduced in women with PCOS, suggesting that the endometrium of PCOS women have a defect in insulin signaling due to GAB1 down-regulation.

Cited by 5 publications

References 22 publications

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis

Expression and function of transient receptor potential channels in the female bovine reproductive tract

Genetics of insulin resistance in polycystic ovary syndrome

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