ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Follicle-stimulating hormone synthesis and fertility depend on SMAD4 and FOXL2.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Gene variants associated with age at menopause are also associated with polycystic ovary syndrome, gonadotrophins and ovarian volume.Human reproduction (Oxford, England) · 2015Trial
- Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.Endocrinology · 2026Article
- Accessibility at a primed distal Fshb-Kcna4 super-enhancer is facilitated by Foxl2 during gonadotrope differentiation.Endocrinology · 2026Article
- Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.bioRxiv : the preprint server for biology · 2025Article
- Chromatin accessibility and transcriptomic profiles of sheep pituitary function associated with fecundity.BMC genomics · 2025Article
- Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.Science (New York, N.Y.) · 2025Article
- Smad4 and FoxH1 potentially interact to regulate cyp19a1a promoter in the ovary of ricefield eel (Monopterus albus).Biology of sex differences · 2024Article
- Single-Cell Transcriptomics Identifies Pituitary Gland Changes in Diet-Induced Obesity in Male Mice.Endocrinology · 2024Article
- A delayed and unsynchronized ovary development as revealed by transcriptome of brain and pituitary ofFrontiers in molecular biosciences · 2024Article
- Oral vaccination with inhibin DNA vaccine for promoting spermatogenesis in rats.Animal reproduction · 2024Article
- Effects of follicle-stimulating hormone on the proliferation and apoptosis of infantile hemangioma stem cells.Biochemistry and biophysics reports · 2023Article
- Imatinib blocks tyrosine phosphorylation of Smad4 and restores TGF-β growth-suppressive signaling in BCR-ABL1-positive leukemia.Signal transduction and targeted therapy · 2023Article
- Construction of a circRNA- lincRNA-lncRNA-miRNA-mRNA ceRNA regulatory network identifies genes and pathways linked to goat fertility.Frontiers in genetics · 2023Article
- A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice.Endocrinology · 2022Article
- Adult-type granulosa cell tumor of the ovary.American journal of cancer research · 2022Review
- SMAD4 Feedback Activates the Canonical TGF-β Family Signaling Pathways.International journal of molecular sciences · 2021Article
- Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB.Endocrinology · 2021Article
- Single nucleus multi-omics regulatory landscape of the murine pituitary.Nature communications · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Follicle-stimulating hormone (FSH) is an essential regulator of gonadal function and fertility. Loss-of-function mutations in the FSHB/Fshb gene cause hypogonadotropic hypogonadism in humans and mice. Both gonadotropin-releasing hormone (GnRH) and activins, members of the transforming growth factor β (TGFβ) superfamily, stimulate FSH synthesis; yet, their relative roles and mechanisms of action in vivo are unknown. Here, using conditional gene-targeting, we show that the canonical mediator of TGFβ superfamily signaling, SMAD4, is absolutely required for normal FSH synthesis in both male and female mice. Moreover, when the Smad4 gene is ablated in combination with its DNA binding cofactor Foxl2 in gonadotrope cells, mice make essentially no FSH and females are sterile. Indeed, the phenotype of these animals is remarkably similar to that of Fshb-knockout mice. Not only do these results establish SMAD4 and FOXL2 as essential master regulators of Fshb transcription in vivo, they also suggest that activins, or related ligands, could play more important roles in FSH synthesis than GnRH.
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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.