ArticleThe Journal of biological chemistry2013
Insulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular Leydig cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 79 citations in OpenAlex.
- Associations between diet quality and testosterone: evidence from mixture and mediation analysis.International urology and nephrology · 2026Article
- Effects of Diet-Induced Obesity and Exercise Intervention on Testicular Germ Cell Health: Modulation of SIRT1/FoxO1 and SIRT1/PGC-1α Signaling Axes.Cell biochemistry and biophysics · 2026Article
- Insulin Resistance, Metabolic Syndrome, and Inflammatory Skin Disease.Journal of clinical medicine · 2026Review
- FromFrontiers in endocrinology · 2026Review
- Review
- Prediction of testosterone deficiency using different screening indexes in adult American men: An NHANES cross-sectional study.PloS one · 2025Article
- Signatures of metabolic diseases on spermatogenesis and testicular metabolism.Nature reviews. Urology · 2024Review
- The Impact of Visceral Adiposity on Testosterone Levels in American Adult Men: A Cross-Sectional Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Regulation of male fertility and accessory gland gene expression by the Drosophila HR39 nuclear receptor.Developmental biology · 2021Article
- Molecular Insulin Actions Are Sexually Dimorphic in Lipid Metabolism.Frontiers in endocrinology · 2021Review
- Absence of glyphosate-induced effects on ovarian folliculogenesis and steroidogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2020Article
- Male Equivalent Polycystic Ovarian Syndrome: Hormonal, Metabolic, and Clinical Aspects.International journal of fertility & sterility · 2020Review
- Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice.Journal of endocrinological investigation · 2020Article
- Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis.Reproductive biology and endocrinology : RB&E · 2020Article
- Developmental Programming: Prenatal Testosterone Excess on Ovarian SF1/DAX1/FOXO3.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Increased DHEAS and Decreased Total Testosterone Serum Levels in a Subset of Men with Early-Onset Androgenetic Alopecia: Does a Male PCOS-Equivalent Exist?International journal of endocrinology · 2020Article
- Farnesoid X receptor alpha (FXRα) is a critical actor of the development and pathologies of the male reproductive system.Cellular and molecular life sciences : CMLS · 2019Review
- The Insulin/IGF System in Mammalian Sexual Development and Reproduction.International journal of molecular sciences · 2019Review
- aThe characteristics of glucose metabolism in the sulfonylurea receptor 1 knockout rat model.Molecular medicine (Cambridge, Mass.) · 2019Article
- The in vitro modulation of steroidogenesis by inflammatory cytokines and insulin in TM3 Leydig cells.Reproductive biology and endocrinology : RB&E · 2018Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Testosterone level is low in insulin-resistant type 2 diabetes. Whether this is due to negative effects of high level of insulin on the testes caused by insulin resistance has not been studied in detail. In this study, we found that insulin directly binds to insulin receptors in Leydig cell membranes and activates phospho-insulin receptor-β (phospho-IR-β), phospho-IRS1, and phospho-AKT, leading to up-regulation of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) gene expression in the MA-10 mouse Leydig cell line. Insulin also inhibits cAMP-induced and liver receptor homolog-1 (LRH-1)-induced steroidogenic enzyme gene expression and steroidogenesis. In contrast, knockdown of DAX-1 reversed insulin-mediated inhibition of steroidogenesis. Whether insulin directly represses steroidogenesis through regulation of steroidogenic enzyme gene expression was assessed in insulin-injected mouse models and high fat diet-induced obesity. In insulin-injected mouse models, insulin receptor signal pathway was activated and subsequently inhibited steroidogenesis via induction of DAX-1 without significant change of luteinizing hormone or FSH levels. Likewise, the levels of steroidogenic enzyme gene expression and steroidogenesis were low, but interestingly, the level of DAX-1 was high in the testes of high fat diet-fed mice. These results represent a novel regulatory mechanism of steroidogenesis in Leydig cells. Insulin-mediated induction of DAX-1 in Leydig cells of testis may be a key regulatory step of serum sex hormone level in insulin-resistant states.
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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.