Rapid Communication: A MicroRNA-132/212 Pathway Mediates GnRH Activation of FSH Expression

Lannes, Jérôme; L’Hôte, David; Garrel, Ghislaine; Laverrière, Jean-Noël; Cohen‐Tannoudji, Joëlle; Quérat, Bruno

doi:10.1210/me.2014-1390

Cited by 53 publications

(48 citation statements)

References 42 publications

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“…Egy másik tanulmány-ban az egér központi idegrendszerének különböző részeit vizsgálva sikerült agyalapimirigyre specifikus miRNS-eket azonosítani [22]. Amellett, hogy a miRNSeknek az emberben is fontos szerepük van a normál mirigy fejlődésében [19,23,24] és hormontermelésében [25][26][27][28][29][30][31], az elmúlt években egyre több humán vizsgálat támasztja alá azt is, hogy részt vehetnek az adenomák kialakulásában és növekedésében [32][33][34][35].…”

Section: Mirns-expressziós Eltérések Az Agyalapimirigy-daganatokbanunclassified

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

et al. 2018

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A mikro-RNS-ek rövid, egyszálú RNS-molekulák, melyek szabályozó szerepüket más gének poszttranszkripcionális módosítása révén fejtik ki. A humán fehérjéket kódoló gének nagyjából 30%-a miRNS-ek szabályozása alatt is áll, aminek révén olyan alapvető folyamatokat befolyásolnak, mint a sejtosztódás, -differenciálódás és sejthalál. Számos daganattípussal kapcsolatban írták már le a megváltozott miRNS-expressziós mintázatot, és egyre több közlemény veti fel, hogy a miRNS-ek, mint terápiás célpontok is szóba jöhetnek. A csökkent expressziójú miRNS-ek adásán, illetve az emelkedett expressziót mutató miRNS-ek gátlásán keresztül nem csak egyetlen gén, hanem egész jelátviteli útvonalak befolyásolása is lehetővé válhat. Az agyalapimirigy-daganatok a leggyakoribb intracranialis tumorok közé tartoznak. Gyakoriságuk ellenére a sporadikusan előforduló adenomák kialakulásának molekuláris mechanizmusa még kevéssé van feltárva. Az utóbbi években egyre több bizonyíték utal arra, hogy a mikro-RNS-eknek fontos szerepük van az adenomagenezisben. Összefoglalónkban az agyalapimirigy-adenomákban leírt miRNS-ek szerepét kíván-juk bemutatni, valamint felvázolni a miRNS-ekhez kapcsolódó terápiás lehetőségeket. Orv Hetil. 2018; 159(7): 252-259. Kulcsszavak: mikro-RNS, agyalapimirigy-adenoma, biomarkerThe role of miRNAs in the pathogenesis of pituitary adenomas MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets. Through adjustment of miRNA levels by artificial miRNAs administration or miRNA inhibition, we can influence not only one target gene but also complex biological pathways. Pituitary adenoma is the second most frequent intracranial tumor. In spite of this, the molecular mechanism of the pituitary adenoma formation is not yet entirely revealed. Recently, more and more evidences have been found suggesting that miRNAs have an important role in pituitary adenoma pathogenesis. Here, we summarize the recent results related to this role and highlight the therapeutic potentials in pituitary adenomas.

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Section: Mirns-expressziós Eltérések Az Agyalapimirigy-daganatokbanunclassified

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

et al. 2018

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“…GnRH stimulation of FSHb (follicle-stimulating hormone, beta polypeptide) expression is dependent on miR-132/212 and involves a Sirtuin1-Forkhead Box O1 pathway. When blocking miR-132/212, total loss of FSH synthesis up-regulation appeared, proposing that this pathway is mandatory for GnRH activation (Lannes et al 2015). GnRH induces expression of multiple miRNAs.…”

Section: Hypothalamus and Pituitarymentioning

confidence: 99%

Progress in micro RNA focused research in endocrinology

Voglova

Bezakova

Herichová

2016

Endocrine Regulations

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Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists' interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex. Today, complete commercially available methodical proposals for miRNA investigation are available. Th ere are techniques allowing the identifi cation of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions. miRNAs have been shown to infl uence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary.

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“…GnRH regulation of Fshb occurs notably through the induction of immediate early genes belonging to the activator protein-1 family [12]. Recently, GnRH was shown to regulate gonadotropin subunit gene transcription by abrogating the repressive effect of FOXO1 [13-15]. GnRH-induced posttranscriptional modifications of FOXO1 result in FOXO1 export from the nucleus, alleviating FOXO1 repression on the Fshb promoter [14, 15].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, GnRH was shown to regulate gonadotropin subunit gene transcription by abrogating the repressive effect of FOXO1 [13-15]. GnRH-induced posttranscriptional modifications of FOXO1 result in FOXO1 export from the nucleus, alleviating FOXO1 repression on the Fshb promoter [14, 15]. In addition to GnRH, the coordinated transcription of gonadotropins relies on several signals, including locally produced activin, follistatin or bone morphogenetic proteins, as well as feedback signals originating from the gonads, such as steroids and inhibin [12].…”

Section: Introductionmentioning

confidence: 99%

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

et al. 2018

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Background/Objectives: Anti-Müllerian hormone (AMH) signaling is critical for sexual differentiation and gonadal function. AMH receptor type 2 (AMHR2) is expressed in extragonadal sites such as brain, and pituitary and emerging evidence indicates that AMH biological action is much broader than initially thought. We recently reported that AMH signaling enhances follicle-stimulating hormone synthesis in pituitary gonadotrope cells. However, mechanisms regulating AMHR2 expression in these extragonadal sites remain to be explored. Method/Results: Here, we demonstrated in perifused murine LβT2 gonadotrope cells that Amhr2 expression is differentially regulated by GnRH pulse frequency with an induction under high GnRH pulsatility. Furthermore, we showed that GnRH transactivates the human AMHR2 promoter in LβT2 cells. Successive deletions of the promoter revealed the importance of a short proximal region (–53/–37 bp) containing an Egr1 binding site. Using site-directed mutagenesis of Egr1 motif and siRNA mediated-knockdown of Egr1, we demonstrated that Egr1 mediates basal and GnRH-dependent activity of the promoter, identifying Egr1 as a new transcription factor controlling hAMHR2 expression. We also showed that SF1 and β-catenin are required for basal promoter activity and demonstrated that both factors contribute to the GnRH stimulatory effect, independently of their respective binding sites. Furthermore, using a constitutively active mutant of FOXO1, we identified FOXO1 as a negative regulator of basal and GnRH-dependent AMHR2 expression in gonadotrope cells. Conclusions: This study identifies GnRH as a regulator of human AMHR2 expression, further highlighting the importance of AMH signaling in the regulation of gonadotrope function.

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Rapid Communication: A MicroRNA-132/212 Pathway Mediates GnRH Activation of FSH Expression

Cited by 53 publications

References 42 publications

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában

Progress in micro RNA focused research in endocrinology

GnRH Transactivates Human AMH Receptor Gene via Egr1 and FOXO1 in Gonadotrope Cells

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