ArticleThe Journal of biological chemistry2005
Induction of cyclin D2 in rat granulosa cells requires FSH-dependent relief from FOXO1 repression coupled with positive signals from Smad.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
93 citing papers in PubMed, 170 citations in OpenAlex.
- Fosl2 Regulates FSH-Dependent Follicle Maturation Through Feedback Amplification of FSH/FSHR Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Developmental and functional landscape of theca cells in ovarian biology.Biological research · 2026Review
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- SOX3 facilitates granulosa cell proliferation and suppresses cell apoptosis through modulating PI3K/AKT pathway by targeting SPP1.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting programmed cell death with natural products: a potential therapeutic strategy for diminished ovarian reserve and fertility preservation.Frontiers in pharmacology · 2025Review
- Anti-Mullerian Hormone InducesCurrent pharmaceutical biotechnology · 2025Article
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- Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development.Genomics, proteomics & bioinformatics · 2024Article
- Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration.Scientific reports · 2024Article
- Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity.Science China. Life sciences · 2024Article
- Uncovering Tumor-Promoting Roles of Activin A in Pancreatic Ductal Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Epiregulin expression and secretion is increased in castration-resistant prostate cancer.Frontiers in oncology · 2023Article
- Spermatogonial fate in mice with increased activin A bioactivity and testicular somatic cell tumours.Frontiers in cell and developmental biology · 2023Article
- Tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K/AKT signaling.Journal of molecular cell biology · 2022Article
- Research and experimental verification of the molecular mechanism of berberine in improving premature ovarian failure based on network pharmacology.Bioengineered · 2022Article
- Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells.International journal of biological sciences · 2022Review
- Sperm-carried IGF2 downregulated the expression of mitogens produced by Sertoli cells: A paracrine mechanism for regulating spermatogenesis?Frontiers in endocrinology · 2022Article
- Protective Effect of Grape Seed Proanthocyanidins on Oxidative Damage of Chicken Follicular Granulosa Cells by Inhibiting FoxO1-Mediated Autophagy.Frontiers in cell and developmental biology · 2022Article
- NORHA, a novel follicular atresia-related lncRNA, promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis.Journal of animal science and biotechnology · 2021Article
- ERβ Regulation of Gonadotropin Responses during Folliculogenesis.International journal of molecular sciences · 2021Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Ovarian follicles undergo exponential growth in response to follicle-stimulating hormone (FSH), largely as a result of the proliferation of granulosa cells (GCs). In vitro under serum-free conditions, rat GCs differentiate in response to FSH but do not proliferate unless activin is also present. In the presence of FSH plus activin, GCs exhibit enhanced expression of cyclin D2 as well as inhibin-alpha, aromatase, steroidogenic factor-1 (SF-1), cholesterol side chain (SCC), and epiregulin. In this report we sought to identify the signaling pathways by which FSH and activin promote GC proliferation and differentiation. Our results show that these responses are associated with prolonged Akt phosphorylation relative to time-matched controls and are dependent on phosphatidylinositol 3-kinase (PI 3-kinase) and Smad2/3 signaling, based on the ability of the PI 3-kinase inhibitor LY294002 or infection with adenoviral dominant negative Smad3 (DN-Smad3) mutant to attenuate induction of cyclin D2, inhibin-alpha, aromatase, SCC, SF-1, and epiregulin. The DN-Smad3 mutant also abolished prolonged Akt phosphorylation stimulated by FSH plus activin 24 h post-treatment. Infection with the adenoviral constitutively active forkhead box-containing protein, O subfamily (FOXO)1 mutant suppressed induction of cyclin D2, aromatase, inhibin-alpha, SF-1, and epiregulin. Transient transfections of GCs with constitutively active FOXO1 mutant also suppressed cyclin D2, inhibin-alpha, and epiregulin promoter-reporter activities. Chromatin immunoprecipitation results demonstrate in vivo the association of FOXO1 with the cyclin D2 promoter in untreated GCs and release of FOXO1 from the cyclin D2 promoter upon addition of FSH plus activin. These results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3.
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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.