ArticleThe Journal of biological chemistry2012
FOXO1 transcription factor inhibits luteinizing hormone β gene expression in pituitary gonadotrope cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- GnRH Promotes Gonadotropin Synthesis and Secretion in the Bovine Anterior Pituitary by Inhibiting METTL1-Mediated m7G Modification of FOXO1 mRNA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Effects of a Reprometabolic Syndrome-Inducing Eucaloric High-Fat Diet on Insulin Sensitivity, Body Composition, the Lipidome, and the Microbiome.Metabolites · 2026Article
- Relationship between Pituitary Gland and Stem Cell in the Aspect of Hormone Production and Disease Prevention: A Narrative Review.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Review
- FOXO Transcription Factors Are Required for Normal Somatotrope Function and Growth.Endocrinology · 2022Article
- Robust differentiation of human enteroendocrine cells from intestinal stem cells.Nature communications · 2022Article
- Neural JNK3 regulates blood flow recovery after hindlimb ischemia in mice via an Egr1/Creb1 axis.Nature communications · 2019Article
- Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity.Scientific reports · 2018Article
- High autophagic flux guards ESC identity through coordinating autophagy machinery gene program by FOXO1.Cell death and differentiation · 2017Article
- Foxo1 Is Required for Normal Somatotrope Differentiation.Endocrinology · 2016Article
- FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes.Molecular and cellular endocrinology · 2015Article
- Gonadotrope-specific deletion of Dicer results in severely suppressed gonadotropins and fertility defects.The Journal of biological chemistry · 2015Article
- Linking diet to acne metabolomics, inflammation, and comedogenesis: an update.Clinical, cosmetic and investigational dermatology · 2015Review
- Article
- Moxibustion Reduces Ovarian Granulosa Cell Apoptosis Associated with Perimenopause in a Natural Aging Rat Model.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).Frontiers in neuroendocrinology · 2014Review
- Fox tales: regulation of gonadotropin gene expression by forkhead transcription factors.Molecular and cellular endocrinology · 2014Review
- Constitutively active FOXO1 diminishes activin induction of Fshb transcription in immortalized gonadotropes.PloS one · 2014Article
- Forkhead box O1 is a repressor of basal and GnRH-induced Fshb transcription in gonadotropes.Molecular endocrinology (Baltimore, Md.) · 2013Article
- FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH.Molecular endocrinology (Baltimore, Md.) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Synthesis of luteinizing hormone (LH) is tightly controlled by a complex network of hormonal signaling pathways that can be modulated by metabolic cues, such as insulin. One group of candidate genes that may be regulated by insulin signaling in pituitary gonadotrope cells is the FOXO subfamily of forkhead transcription factors. In this study we investigated whether FOXO1 is expressed in gonadotropes and if it can modulate LH β-subunit (Lhb) gene expression. We demonstrated that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K-dependent manner. We also showed that FOXO1 repressed basal transcription and gonadotropin-releasing hormone (GnRH) induction of both the murine and human LHB genes in LβT2 cells, suggesting that FOXO1 regulation of LHB transcription may be conserved between rodents and humans. Although we did not detect FOXO1 binding to the proximal Lhb promoter, the FOXO1 DNA binding domain was necessary for the suppression, suggesting that FOXO1 exerts its effect through protein-protein interactions with transcription factors/cofactors required for Lhb gene expression. FOXO1 repression mapped to the proximal Lhb promoter containing steroidogenic factor 1 (SF1), pituitary homeobox 1 (PTX1), and early growth response protein 1 (EGR1) binding elements. Additionally, FOXO1 blocked induction of the Lhb promoter with overexpressed SF1, PTX1, and EGR1, indicating that FOXO1 repression occurs via these transcription factors but not through regulation of their promoters. In summary, we demonstrate that FOXO1 phosphorylation and cellular localization is regulated by insulin signaling in gonadotropes and that FOXO1 inhibits Lhb transcription. Our study also suggests that FOXO1 may play an important role in controlling LH levels in response to metabolic cues.
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Registered trials
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.