ArticleMolecular and cellular biology2011
Calcineurin mediates the gonadotropin-releasing hormone effect on expression of both subunits of the follicle-stimulating hormone through distinct mechanisms.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Stimulus-Induced Activation of the Glycoprotein Hormone α-Subunit Promoter in Human Placental Choriocarcinoma Cells: Major Role of a tandem cAMP Response Element.Current issues in molecular biology · 2024Article
- Article
- Epigenetic repression of gonadotropin gene expression via a GnRH-mediated DNA delivery system.Gene therapy · 2022Article
- Unravelling the role of epigenetics in reproductive adaptations to early-life environment.Nature reviews. Endocrinology · 2020Review
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
- Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression.Molecular and cellular endocrinology · 2018Review
- Multifaceted Targeting of the Chromatin Mediates Gonadotropin-Releasing Hormone Effects on Gene Expression in the Gonadotrope.Frontiers in endocrinology · 2018Review
- Mitogen- and stress-activated protein kinase 1 is required for gonadotropin-releasing hormone-mediated activation of gonadotropin α-subunit expression.The Journal of biological chemistry · 2017Article
- A pupal transcriptomic screen identifies Ral as a target of store-operated calcium entry in Drosophila neurons.Scientific reports · 2017Article
- RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Gonadotropin-releasing hormone-regulated prohibitin mediates apoptosis of the gonadotrope cells.Molecular endocrinology (Baltimore, Md.) · 2013Article
- GnRH-Induced Ca(2+) Signaling Patterns and Gonadotropin Secretion in Pituitary Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary Physiological Demands.Frontiers in endocrinology · 2013Review
- GnRH regulation of Jun and Atf3 requires calcium, calcineurin, and NFAT.Molecular endocrinology (Baltimore, Md.) · 2012Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gonadotropin-releasing hormone (GnRH) regulates the expression of all three gonadotropin genes, encoding the common α subunit (αGSU) and hormone-specific β subunits, through the activation of several signal transduction pathways. We have shown that GnRH also upregulates calcineurin, and we hypothesized that calcineurin mediates the effects of GnRH on the transcription of the αGSU and follicle-stimulating hormone β (FSHβ) genes through two of its targets: nuclear factor of activated T cells (NFAT) and CREB-regulated transcription coactivator (TORC). We show that calcineurin is essential for GnRH-induced expression of both genes but that NFAT and TORC1 play quite distinct roles in activating each gene. GnRH induces calcineurin-dependent nuclear import of NFAT3, which activates the αGSU promoter, while TORC1 also mediates GnRH activation of this promoter, but not through CREB. GnRH initially stimulates the degradation of TORC1 but protects the N terminus of the newly synthesized protein to enhance its activity. Calcineurin induces Nur77 expression, likely via NFAT3, and Nur77 interacts synergistically with TORC1 and CREB to increase FSHβ promoter activity. Although TORC plays a role in the basal activity of the FSHβ promoter, it does not interact with phosphorylated CREB and probably does not play a major role in direct GnRH signaling to this gene. TORC may be part of an alternatively regulated pathway, possibly involving cross talk with other stimulatory hormones.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.