ArticleMolecular and cellular biology2012
CREB binding protein (CBP) activation is required for luteinizing hormone beta expression and normal fertility in mice.
Article in Molecular and cellular biology, 2012. 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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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Phospholipase Cβ regulates negative associative memory through calcium dependent and independent mechanisms.The Journal of biological chemistry · 2026Article
- Discovery proteomics identification of factors contributing to gonadotropin β expression.Endocrinology · 2026Article
- Stimulus-Transcription Coupling of TRPM3 Channels: A Signaling Pathway from the Plasma Membrane to the Nucleus.Biomolecules · 2025Review
- Transcriptional and Histone Acetylation Changes Associated with CRE Elements Expose Key Factors Governing the Regulatory Circuit in the Early Stage of Huntington's Disease Models.International journal of molecular sciences · 2023Article
- Age-associated changes in gene expression in the anterior pituitary glands of female Japanese black cattle.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Article
- Regulation of reproduction via tight control of gonadotropin hormone levels.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
- Egr-1 regulates RTA transcription through a cooperative involvement of transcriptional regulators.Oncotarget · 2017Article
- Systematic Analysis of Protein Interaction Network Associated with Azoospermia.International journal of molecular sciences · 2016Article
- FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes.Molecular and cellular endocrinology · 2015Article
- The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).Frontiers in neuroendocrinology · 2014Review
- The Myb-p300-CREB axis modulates intestine homeostasis, radiosensitivity and tumorigenesis.Cell death & disease · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Normal function of the hypothalamic-pituitary-gonadal axis is dependent on gonadotropin-releasing hormone (GNRH)-stimulated synthesis and secretion of luteinizing hormone (LH) from the pituitary gonadotroph. While the transcriptional coactivator CREB binding protein (CBP) is known to interact with Egr-1, the major mediator of GNRH action on the Lhb gene, the role of CBP in Lhb gene expression has yet to be characterized. We show that in the LβT2 gonadotroph cell line, overexpression of CBP augmented the response to GNRH and that knockdown of CBP eliminated GNRH responsiveness. While GNRH-mediated phosphorylation of CBP at Ser436 increased the interaction with Egr-1 on the Lhb promoter, loss of this phosphorylation site eliminated GNRH-mediated Lhb expression in LβT2 cells. In vivo, loss of CBP phosphorylation at Ser436 rendered female mice subfertile. S436A knock-in mice had disrupted estrous cyclicity and reduced responsiveness to GNRH. Our results show that GNRH-mediated phosphorylation of CBP at Ser436 is required for Egr-1 to activate Lhb expression and is a requirement for normal fertility in female mice. As CBP can be phosphorylated by other factors, such as insulin, our studies suggest that CBP may act as a key regulator of Lhb expression in the gonadotroph by integrating homeostatic information with GNRH signaling.
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Registered trials
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