ArticleThe Journal of biological chemistry2015
Gonadotrope-specific deletion of Dicer results in severely suppressed gonadotropins and fertility defects.
Article in The Journal of biological chemistry, 2015. 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, 45 citations in OpenAlex.
- Profile of Rat Adrenal microRNAs Induced by Gonadectomy and Testosterone or Estradiol Replacement.International journal of molecular sciences · 2025Article
- RNA-seq analysis identifies age-dependent changes in expression of mRNAs - encoding N-glycosylation pathway enzymes in mouse gonadotropes.Molecular and cellular endocrinology · 2023Article
- Peptidylarginine deiminase 2 regulates expression of DGCR8 affecting miRNA biogenesis in gonadotrope cells.Reproduction (Cambridge, England) · 2023Article
- Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.Nature communications · 2022Article
- Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine.Human reproduction update · 2022Review
- Review
- Emerging Roles of Epigenetics in the Control of Reproductive Function: Focus on Central Neuroendocrine Mechanisms.Journal of the Endocrine Society · 2021Review
- Post-Transcriptional Regulation ofInternational journal of molecular sciences · 2021Review
- Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies.International journal of molecular sciences · 2020Review
- Human Follicle-Stimulating Hormone ß Subunit Expression Depends on FOXL2 and SMAD4.Endocrinology · 2020Article
- The role of miRNAs in regulating adrenal and gonadal steroidogenesis.Journal of molecular endocrinology · 2020Review
- Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.Reproduction (Cambridge, England) · 2019Article
- MiR-125b-2 Knockout in Testis Is Associated with Targeting to the PAP Gene, Mitochondrial Copy Number, and Impaired Sperm Quality.International journal of molecular sciences · 2019Article
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
- Mouse models for the analysis of gonadotropin secretion and action.Best practice & research. Clinical endocrinology & metabolism · 2018Review
- Molecular regulation of follicle-stimulating hormone synthesis, secretion and action.Journal of molecular endocrinology · 2018Review
- Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility.The Journal of clinical investigation · 2017Article
- MicroRNA-7a2 suppression causes hypogonadotropism and uncovers signaling pathways in gonadotropes.The Journal of clinical investigation · 2017Article
- Creating conditional dual fluorescence labeled transgenic animals for studying function of small noncoding RNAs.Connective tissue research · 2017Article
- Evaluation of in vivo bioactivities of recombinant hypo- (FSHMolecular and cellular endocrinology · 2016Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone are heterodimeric glycoproteins expressed in gonadotropes. They act on gonads and promote their development and functions including steroidogenesis and gametogenesis. Although transcriptional regulation of gonadotropin subunits has been well studied, the post-transcriptional regulation of gonadotropin subunits is not well understood. To test if microRNAs regulate the hormone-specific gonadotropin β subunits in vivo, we deleted Dicer in gonadotropes by a Cre-lox genetic approach. We found that many of the DICER-dependent microRNAs, predicted in silico to bind gonadotropin β subunit mRNAs, were suppressed in purified gonadotropes of mutant mice. Loss of DICER-dependent microRNAs in gonadotropes resulted in profound suppression of gonadotropin-β subunit proteins and, consequently, the heterodimeric hormone secretion. In addition to suppression of basal levels, interestingly, the post-gonadectomy-induced rise in pituitary gonadotropin synthesis and secretion were both abolished in mutants, indicating a defective gonadal negative feedback control. Furthermore, mutants lacking Dicer in gonadotropes displayed severely reduced fertility and were rescued with exogenous hormones confirming that the fertility defects were secondary to suppressed gonadotropins. Our studies reveal that DICER-dependent microRNAs are essential for gonadotropin homeostasis and fertility in mice. Our studies also implicate microRNAs in gonadal feedback control of gonadotropin synthesis and secretion. Thus, DICER-dependent microRNAs confer a new layer of transcriptional and post-transcriptional regulation in gonadotropes to orchestrate the hypothalamus-pituitary-gonadal axis physiology.
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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.