ArticleEndocrinology2018
Conditional Deletion of FOXL2 and SMAD4 in Gonadotropes of Adult Mice Causes Isolated FSH Deficiency.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- 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.Endocrinology · 2026Article
- Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.bioRxiv : the preprint server for biology · 2025Article
- A Point Mutation in an Otherwise Dispensable Upstream Fshb Enhancer Moderately Impairs Fertility in Female Mice.Endocrinology · 2025Article
- Smad4 and FoxH1 potentially interact to regulate cyp19a1a promoter in the ovary of ricefield eel (Monopterus albus).Biology of sex differences · 2024Article
- Article
- Selected Genetic Factors Associated with Primary Ovarian Insufficiency.International journal of molecular sciences · 2023Review
- Revisiting the gonadotropic regulation of mammalian spermatogenesis: evolving lessons during the past decade.Frontiers in endocrinology · 2023Review
- Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice.Endocrinology · 2022Article
- Article
- Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB.Endocrinology · 2021Article
- Development of a Highly Sensitive ELISA for Measurement of FSH in Serum, Plasma, and Whole Blood in Mice.Endocrinology · 2021Article
- Increased FOXL2 expression alters uterine structures and functions†.Biology of reproduction · 2020Article
- SMAD-FOXL2 Regulation of FSHB: A Game of Human and Mouse.Endocrinology · 2020Article
- Murine FSH Production Depends on the Activin Type II Receptors ACVR2A and ACVR2B.Endocrinology · 2020Article
- Human Follicle-Stimulating Hormone ß Subunit Expression Depends on FOXL2 and SMAD4.Endocrinology · 2020Article
- Gonadotrope-specific deletion of the BMP type 2 receptor does not affect reproductive physiology in mice†‡.Biology of reproduction · 2020Article
- Addition of an N-Terminal Poly-Glutamate Fusion Tag Improves Solubility and Production of Recombinant TAT-Cre Recombinase inJournal of microbiology and biotechnology · 2020Article
- Rationale and Roadmap for Developing Panels of Hotspot Cancer Driver Gene Mutations as Biomarkers of Cancer Risk.Environmental and molecular mutagenesis · 2020Review
- TGF-β Superfamily Regulation of Follicle-Stimulating Hormone Synthesis by Gonadotrope Cells: Is There a Role for Bone Morphogenetic Proteins?Endocrinology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The glycoprotein FSH, a product of pituitary gonadotrope cells, regulates ovarian follicle development in females and spermatogenesis in males. FSH is a heterodimer of the common α gonadotropin subunit and the hormone-specific FSHβ subunit (a product of the Fshb gene). Using a conditional knockout approach (Cre-lox), we previously demonstrated that Fshb expression in mice depends on the transcription factors forkhead box L2 (FOXL2) and SMAD4. Deletion of Foxl2 or Smad4 alone led to FSH deficiency, female subfertility, and oligozoospermia in males. Simultaneous deletion of the two genes yielded a greater suppression of FSH and female sterility. The Cre-driver used previously was first active during embryonic development. Therefore, it is unclear whether FOXL2 and SMAD4 play important roles in the development or adult function of gonadotropes, or both. To address this question, we developed a tamoxifen-inducible Cre-driver line, which enabled Foxl2 and Smad4 gene deletions in gonadotropes of adult mice. After tamoxifen treatment, females with previously demonstrated fertility exhibited profound reductions in FSH levels, arrested ovarian follicle development, and sterility. FSH levels were comparably reduced in males 1 or 2 months after treatment; however, spermatogenesis was unaffected. These data indicate that (1) FOXL2 and SMAD4 are necessary to maintain FSH synthesis in gonadotrope cells of adult mice, (2) FSH is essential for female reproduction but appears to be unnecessary for the maintenance of spermatogenesis in adult male mice, and (3) the inducible Cre-driver line developed here provides a powerful tool to interrogate gene function in gonadotrope cells of adult mice.
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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.