ArticleMolecular endocrinology (Baltimore, Md.)2013
GnRH pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of PKA and CREB.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- GnRH pulse frequency is decoded by distinct GαHormones (Athens, Greece) · 2026Article
- Molecular Mechanisms of Dysregulated LH and FSH Secretion in Human Reproductive Failure.Biomedicines · 2026Review
- GnRH-driven FTO-mediated RNA mBMC biology · 2024Article
- Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel MarkerInternational journal of molecular sciences · 2024Article
- Article
- Integrative Proteomics and Phosphoproteomics Analysis of the Rat Adenohypophysis after GnRH Treatment.International journal of molecular sciences · 2023Article
- Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase.Animals : an open access journal from MDPI · 2022Article
- Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice.Endocrinology · 2022Article
- The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones.Frontiers in immunology · 2022Review
- Article
- Regulation of FSH Synthesis by Differentially Expressed miR-488 in Anterior Adenohypophyseal Cells.Animals : an open access journal from MDPI · 2021Article
- Identification of Circular RNAs in the Anterior Pituitary in Rats Treated with GnRH.Animals : an open access journal from MDPI · 2021Article
- Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion.Animals : an open access journal from MDPI · 2021Review
- Carbon Black Nanoparticles Selectively Alter Follicle-Stimulating Hormone ExpressionFrontiers in neuroscience · 2021Article
- Hypothalamic Transcriptome Analysis Reveals the Crucial MicroRNAs and mRNAs Affecting Litter Size in Goats.Frontiers in veterinary science · 2021Article
- Review
- Gpr120 mRNA expression in gonadotropes in the mouse pituitary gland is regulated by free fatty acids.The Journal of reproduction and development · 2020Article
- Short-term but not long-term high-fat diet induces an increase in gene expression of gonadotropic hormones and GPR120 in the male mouse pituitary gland.The Journal of reproduction and development · 2020Article
- Regulation and Function of C-Type Natriuretic Peptide (CNP) in Gonadotrope-Derived Cell Lines.Cells · 2019Article
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Expression of pituitary FSH and LH, under the control of pulsatile GnRH, is essential for fertility. cAMP response element-binding protein (CREB) has been implicated in the regulation of FSHβ gene expression, but the molecular mechanisms by which pulsatile GnRH regulates CREB activation remain poorly understood. We hypothesized that CREB is activated by a distinct signaling pathway in response to pulsatile GnRH in a frequency-dependent manner to dictate the FSHβ transcriptional response. GnRH stimulation of CREB phosphorylation (pCREB) in the gonadotrope-derived LβT2 cell line was attenuated by a protein kinase A (PKA) inhibitor, H89. A dominant negative PKA (DNPKA) reduced GnRH-stimulated pCREB and markedly decreased GnRH stimulation of FSHβ mRNA and FSHβLUC activity, but had little effect on LHβLUC activity, indicating relative specificity of this pathway. In perifusion studies, FSHβ mRNA levels and FSHβLUC activities were increased by pulsatile GnRH, with significantly greater increases at low compared with high pulse frequencies. DNPKA markedly reduced these GnRH-stimulated FSHβ responses at both low and high pulse frequencies. Correlating with FSHβ activation, both PKA activity and levels of pCREB were increased to a greater extent by low compared with high GnRH pulse frequencies, and the induction of pCREB was also attenuated by overexpression of DNPKA at both low and high pulse frequencies. Taken together, these data indicate that a PKA-mediated signaling pathway mediates GnRH activation of CREB at low-pulse frequencies, playing a significant role in the decoding of the hypothalamic GnRH signal to result in frequency-dependent FSHβ activation.
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