ArticleEndocrinology2015
GATA4 is a key regulator of steroidogenesis and glycolysis in mouse Leydig cells.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 51 citations in OpenAlex.
- Serine Ameliorates Cadmium-Induced Testicular Injury by Regulating the PGAM1/PHGDH Signaling Pathway.Journal of biochemical and molecular toxicology · 2026Article
- The impact of furan exposure on steroidogenesis in Leydig cells: cellular and molecular observations.Molecular biology reports · 2024Article
- Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis.Stem cell research & therapy · 2024Review
- Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- A Short Promoter Region Containing Conserved Regulatory Motifs Is Required for Steroidogenic Acute Regulatory Protein (International journal of molecular sciences · 2022Article
- High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort.Journal of the Endocrine Society · 2022Article
- Testicular Macrophages Produce Progesterone De Novo Promoted by cAMP and Inhibited by M1 Polarization Inducers.Biomedicines · 2022Article
- Insights Into the Roles of GATA Factors in Mammalian Testis Development and the Control of Fetal Testis Gene Expression.Frontiers in endocrinology · 2022Review
- Effects of 4% paraformaldehyde and modified Davidson's fluid on the morphology and immunohistochemistry of Xiang pig testes.Journal of toxicologic pathology · 2020Article
- Analysis of variants in GATA4 and FOG2/ZFPM2 demonstrates benign contribution to 46,XY disorders of sex development.Molecular genetics & genomic medicine · 2020Article
- Article
- The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis.Cellular and molecular life sciences : CMLS · 2019Review
- Article
- Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors.Reproduction (Cambridge, England) · 2017Article
- GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli Cells.Endocrinology · 2016Article
- GATA factors in endocrine neoplasia.Molecular and cellular endocrinology · 2016Review
- GATA4 and GATA6 Knockdown During Luteinization Inhibits Progesterone Production and Gonadotropin Responsiveness in the Corpus Luteum of Female Mice.Biology of reproduction · 2015Article
- Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis.Reproduction (Cambridge, England) · 2015Article
- Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.Genes & developmentArticle
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Transcription factor GATA4 is expressed in somatic cells of the mammalian testis. Gene targeting studies in mice have shown that GATA4 is essential for proper differentiation and function of Sertoli cells. The role of GATA4 in Leydig cell development, however, remains controversial, because targeted mutagenesis experiments in mice have not shown a consistent phenotype, possibly due to context-dependent effects or compensatory responses. We therefore undertook a reductionist approach to study the function of GATA4 in Leydig cells. Using microarray analysis and quantitative RT-PCR, we identified a set of genes that are down-regulated or up-regulated after small interfering RNA (siRNA)-mediated silencing of Gata4 in the murine Leydig tumor cell line mLTC-1. These same genes were dysregulated when primary cultures of Gata4(flox/flox) adult Leydig cells were subjected to adenovirus-mediated cre-lox recombination in vitro. Among the down-regulated genes were enzymes of the androgen biosynthetic pathway (Cyp11a1, Hsd3b1, Cyp17a1, and Srd5a). Silencing of Gata4 expression in mLTC-1 cells was accompanied by reduced production of sex steroid precursors, as documented by mass spectrometric analysis. Comprehensive metabolomic analysis of GATA4-deficient mLTC-1 cells showed alteration of other metabolic pathways, notably glycolysis. GATA4-depleted mLTC-1 cells had reduced expression of glycolytic genes (Hk1, Gpi1, Pfkp, and Pgam1), lower intracellular levels of ATP, and increased extracellular levels of glucose. Our findings suggest that GATA4 plays a pivotal role in Leydig cell function and provide novel insights into metabolic regulation in this cell type.
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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.