ArticleMolecular endocrinology (Baltimore, Md.)2015
Homeodomain Proteins SIX3 and SIX6 Regulate Gonadotrope-specific Genes During Pituitary Development.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Genome-wide association analysis reveals genetic architecture of fertility traits in Sahiwal heifers and cows.Tropical animal health and production · 2026Article
- The Chronological Trigger: The Orchestra Between Homeobox Genes and the Circadian Clock During Development.Biology of the cell · 2025Review
- Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells.Endocrinology · 2021Article
- Androgen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes.Molecular and cellular endocrinology · 2021Article
- A fish with no sex: gonadal and adrenal functions partition between zebrafish NR5A1 co-orthologs.Genetics · 2021Article
- The SIX Family of Transcription Factors: Common Themes Integrating Developmental and Cancer Biology.Frontiers in cell and developmental biology · 2021Review
- The pink salmon genome: Uncovering the genomic consequences of a two-year life cycle.PloS one · 2021Article
- Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.Frontiers in genetics · 2021Article
- Augmentation ofJournal of the Endocrine Society · 2020Article
- Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency.International journal of molecular sciences · 2020Article
- Article
- Dysregulation of Hypothalamic Gene Expression and the Oxytocinergic System by Soybean Oil Diets in Male Mice.Endocrinology · 2020Article
- Transcription Profiles of Age-at-Maturity-Associated Genes Suggest Cell Fate Commitment Regulation as a Key Factor in the Atlantic Salmon Maturation Process.G3 (Bethesda, Md.) · 2020Article
- Deletion of the Homeodomain Protein Six6 From GnRH Neurons Decreases GnRH Gene Expression, Resulting in Infertility.Endocrinology · 2019Article
- Identification of a pituitary ERα-activated enhancer triggering the expression of Nr5a1, the earliest gonadotrope lineage-specific transcription factor.Epigenetics & chromatin · 2019Article
- Functional Annotation of the Transcriptome of the Pig,Frontiers in genetics · 2019Article
- Cell Type- and Sex-Dependent Transcriptome Profiles of Rat Anterior Pituitary Cells.Frontiers in endocrinology · 2019Article
- Molecular regulation of follicle-stimulating hormone synthesis, secretion and action.Journal of molecular endocrinology · 2018Review
- WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome.EMBO reports · 2018Article
- Regulatory Architecture of the LβT2 Gonadotrope Cell Underlying the Response to Gonadotropin-Releasing Hormone.Frontiers in endocrinology · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Sine oculis-related homeobox 3 (SIX3) and SIX6, 2 closely related homeodomain transcription factors, are involved in development of the mammalian neuroendocrine system and mutations of Six6 adversely affect fertility in mice. We show that both small interfering RNA knockdown in gonadotrope cell lines and knockout of Six6 in both embryonic and adult male mice (Six6 knockout) support roles for SIX3 and SIX6 in transcriptional regulation in gonadotrope gene expression and that SIX3 and SIX6 can functionally compensate for each other. Six3 and Six6 expression patterns in gonadotrope cell lines reflect the timing of the expression of pituitary markers they regulate. Six3 is expressed in an immature gonadotrope cell line and represses transcription of the early lineage-specific pituitary genes, GnRH receptor (GnRHR) and the common α-subunit (Cga), whereas Six6 is expressed in a mature gonadotrope cell line and represses the specific β-subunits of LH and FSH (LHb and FSHb) that are expressed later in development. We show that SIX6 repression requires interaction with transducin-like enhancer of split corepressor proteins and competition for DNA-binding sites with the transcriptional activator pituitary homeobox 1. Our studies also suggest that estradiol and circadian rhythm regulate pituitary expression of Six6 and Six3 in adult females but not in males. In summary, SIX3 and SIX6 play distinct but compensatory roles in regulating transcription of gonadotrope-specific genes as gonadotrope cells differentiate.
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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.