FSH stimulates IRS-2 expression in human granulosa cells through cAMP/SP1, an inoperative FSH action in PCOS patients

Anjali, G.; Kaur, Surleen; Lakra, Ruchi; Taneja, Jyoti; Kalsey, Gaganjot Singh; Nagendra, A; Shrivastav, Tulsidas G.; Devi, M. Gouri; Malhotra, Neena; Kriplani, Alka; Singh, Rita

doi:10.1016/j.cellsig.2015.09.011

Cited by 36 publications

(60 citation statements)

References 54 publications

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“…Our results were similar to the results of a previous study which showed that the expression of miR-431 decreased in rat ova ry following human chorionic gonadotropin administration [21]. In addition, our research further concluded that FSH can activate IRS2 and AKT signaling pathway in granulosa cells [3,23].…”

Section: Discussionsupporting

confidence: 92%

“…Among them, FSH is an essential regulator of folliculogenesis, particularly in regulating the proliferation of granulosa cells and steroidogenesis. A previous study reported that FSH stimulates insulin receptor substrate 2 (IRS2) expression in human and rat granulosa cells [3].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, increasing number of studies have shown that miRNAs participate in the regulation of ovarian development [11][12][13][14][15][16][17]. A prior study revealed that IRS2 was upregulated in FSH-treated human [3,18] and rat granulosa cells [18]. Further, some studies have suggested that miRNAs, including miR-431, can be regulated by hormones in granulosa cells [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway

Yang

Liu

et al. 2020

Journal of Reproduction and Development

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MicroRNAs (miRNAs) regulate the functions of granulosa cells by interacting with their target mRNAs. Insulin receptor substrate 2 (IRS2) is one of the targets of miR-431 and can be regulated by ovarian hormones. However, the role of miR-431 and the associated signal transduction pathway in ovarian development has not been studied previously. In this study, we first analyzed the expression of miR-431 and IRS2 following stimulation with pregnant mare serum gonadotropin (PMSG) during the estrous cycle or different stages of ovarian development in mice. Subs equently, we investigated the role, function, and signaling pathway of miR-431 in the human granulosa cell line, COV434. The results showed that follicle stimulating hormone (FSH) gradually decreased miR-431 levels, induced IRS2, and promoted pAKT expression. Moreover, miR-431 overexpression and IRS2 knockdown attenuated AKT activation, inhibited cell proliferation, and decreased estradiol (E 2) and progesterone (P 4) synthesis. Further, luciferase reporter assay demonstrated that IRS2 was a direct target of miR-431. In conclusion, this study demonstrated that miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway

Yang

Liu

et al. 2020

Journal of Reproduction and Development

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“…Among other IRS modulatory mechanisms, it is worth mentioning about expression regulation of IRS mediated by hyperinsulinemia and other hormones [30]. Anjali et al showed that FSH (follicle stimulating hormone) induces expression of IRS2 in granulosa cells [31]. Also, some natural medicines like Tangzhiqing formula, a mix of five herbs, modulate IRS expression level in HEPG2 cells (IR1 and IRS2) and L-6 myotubes (IRS1) [32].…”

Section: Overview Of Three Major Mechanisms Affecting Irs-dependent Smentioning

confidence: 99%

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Świderska¹,

Strycharz²,

Wróblewski³

et al. 2020

Blood Glucose Levels

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Glucose uptake is regulated by several mechanisms, where insulin plays the most prominent role. This powerful anabolic hormone regulates the transport of glucose into the cell through translocation of glucose transporter from an intracellular pool to the plasma membrane mainly in metabolically active tissues like skeletal muscles, adipose tissue, or liver (GLUT4). This translocation occurs through multiple steps of PI3K/AKT signaling pathway. In this chapter, we will focus on molecular events leading to GLUT4 translocation, starting with activation of insulin receptors through signaling cascade involving phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) and finally, the action of their effectors. We will present regulatory mechanisms and modulators of insulin-mediated glucose uptake.

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“…To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al, 2005 [1] ). The ibid data is part of author׳s publication (Anjali et al, 2015 [2] ) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code.…”

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confidence: 99%

Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter

et al. 2016

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Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer.

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FSH stimulates IRS-2 expression in human granulosa cells through cAMP/SP1, an inoperative FSH action in PCOS patients

Cited by 36 publications

References 54 publications

miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway

miR-431 regulates granulosa cell function through the IRS2/PI3K/AKT signaling pathway

Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake

Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter

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