ArticleThe Journal of clinical endocrinology and metabolism2015
FSH Regulates IGF-2 Expression in Human Granulosa Cells in an AKT-Dependent Manner.
Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
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- Quantitative proteomic analysis of pathological and physiological ovarian aging: model evaluation, molecular mechanisms, and identification of early biomarkers and therapeutic targets.Journal of ovarian research · 2025Article
- Study on the Function ofAnimals : an open access journal from MDPI · 2025Article
- Decoding androgen excess in polycystic ovary syndrome: Roles of insulin resistance and other key intraovarian and systemic factors.World journal of diabetes · 2025Review
- The Differentiation Fate of Granulosa Cells and the Regulatory Mechanism in Ovary.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Acupuncture Increased the Number of Retrieved Oocytes in a Mouse Model of POR: The Involvement of DNA Methylation in the Oocytes.Combinatorial chemistry & high throughput screening · 2025Article
- Follicular Atresia in Buffalo: Cocaine- and Amphetamine-Regulated Transcript (CART) and the Underlying Mechanisms.Animals : an open access journal from MDPI · 2024Article
- Integrated transcriptomic analysis on chicken ovary reveals CYP21A1 affects follicle granulosa cell development and steroid hormone synthesis.Poultry science · 2024Article
- Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing.Science advances · 2024Article
- Pleomorphic adenoma gene1 in reproduction and implication for embryonic survival in cattle: a review.Journal of animal science · 2024Review
- Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity.Science China. Life sciences · 2024Article
- Genome-wide selective signatures mining the candidate genes for egg laying in goose.BMC genomics · 2023Article
- Human-relevant exposure to di-n-butyl phthalate tampers with the ovarian insulin-like growth factor 1 system and disrupts folliculogenesis in young adult mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Porcine Follicular Fluid-Derived Exosome: The Pivotal Material for Porcine Oocyte Maturation in Lipid Antioxidant Activity.International journal of molecular sciences · 2023Article
- Differentiation of uniparental human embryonic stem cells into granulosa cells reveals a paternal contribution to gonadal development.Stem cell reports · 2023Article
- Insulin-like growth factor 1 enhances follicle-stimulating hormone-induced phosphorylation of GATA4 in rat granulosa cells.Molecular and cellular endocrinology · 2023Article
- Combined synchronization and superovulation treatments negatively impact embryo viability possibly by the downregulation of WNT/β-catenin and Notch signaling genes in the porcine endometrium.Journal of animal science · 2022Article
- Article
- Autophagy regulates differentiation of ovarian granulosa cells through degradation of WT1.Autophagy · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
contextIGF-2 is highly expressed in the granulosa cells of human dominant ovarian follicles; however, little is known about the regulation of the IGF-2 gene or the interaction of IGF-2 and FSH during follicle development.
objectiveTo examine the mechanisms involved in the regulation of the IGF-2 gene by FSH and the interplay between FSH and IGF-2 during granulosa cell differentiation. Design, Setting, Patients, and Interventions: Cumulus granulosa cells were separated from cumulus-oocyte complexes isolated from the follicular aspirates of in vitro fertilization patients and cultured for in vitro studies. MAIN OUTCOME: Protein and mRNA levels of IGF-2 and CYP19A1 (aromatase) were quantified using Western blot and quantitative real-time PCR. IGF-2 promoter-specific activation was determined by the amplification of alternative exons by PCR. Cell proliferation was assessed after treatment with FSH and/or IGF-2.
resultsFSH significantly enhanced IGF-2 expression after 8 hours of treatment and at low doses (1 ng/mL). Reciprocally, IGF-2 synergized with FSH to increase cell proliferation and the expression of CYP19A1. When IGF-2 activity was blocked, FSH was no longer able to stimulate CYP19A1 expression. Determination of IGF-2 promoter usage in human cumulus cells showed that the IGF-2 gene is driven by promoters P3 and P4. However, FSH exclusively increased P3 promoter-derived transcripts. Moreover, the FSH-induced stimulation of P3-driven IGF-2 transcripts was blocked by cotreatment with inhibitors of AKT or IGF-1 receptor (IGF-1R). The inhibitory effect of the IGF-1R inhibitor on FSH-induced IGF-2 mRNA accumulation was reversed by overexpression of a constitutively active AKT construct.
conclusionsFSH is a potent enhancer of IGF-2 expression in human granulosa cells. In return, IGF-2 activation of the IGF-1R and AKT is required for FSH to stimulate CYP19A1 expression and proliferation of granulosa cells. These findings suggest a positive loop interaction between FSH and IGF-2 that is critical for human granulosa cell proliferation and differentiation.
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