ArticleEndocrine2016
SF-1 deficiency causes lipid accumulation in Leydig cells via suppression of STAR and CYP11A1.
Article in Endocrine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- YAP/TEAD complex restricts H3K27ac deposition to suppress testosterone synthesis in adult Leydig cells.Histochemistry and cell biology · 2026Article
- Transcriptomic Profiling of Canine Testicular Leydig Cell Tumors Uncovers Key Upregulated Gene Pathways.Animals : an open access journal from MDPI · 2026Article
- Effect of whole-plant mulberry supplementation on testis development and antioxidant capacity in Hu rams.Animal bioscience · 2025Article
- SARS-CoV-2 exploits steroidogenic machinery, triggers lipid metabolism for viral replication and induces immune response in Leydig cells of K18-hACE2 mice.Frontiers in cellular and infection microbiology · 2025Article
- Role ofCurrent issues in molecular biology · 2024Review
- Effects of Bushen Yiyuan recipe on testosterone synthesis in Leydig cells of rats with exercise-induced low serum testosterone levels.Pharmaceutical biology · 2022Article
- Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers.International journal of molecular sciences · 2022Review
- Testicular Macrophages Produce Progesterone De Novo Promoted by cAMP and Inhibited by M1 Polarization Inducers.Biomedicines · 2022Article
- Transcription Factors in the Regulation of Leydig Cell Gene Expression and Function.Frontiers in endocrinology · 2022Review
- Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Effects of increasing intake of soybean oil on synthesis of testosterone in Leydig cells.Nutrition & metabolism · 2021Article
- Role of Constitutive STAR in Leydig Cells.International journal of molecular sciences · 2021Article
- A fish with no sex: gonadal and adrenal functions partition between zebrafish NR5A1 co-orthologs.Genetics · 2021Article
- Conversion of Fibroblast into Functional Leydig-like Cell Using Defined Small Molecules.Stem cell reports · 2020Article
- Article
- Steroidogenic acute regulatory protein transcription is regulated by estrogen receptor signaling in largemouth bass ovary.General and comparative endocrinology · 2020Article
- The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis.Cellular and molecular life sciences : CMLS · 2019Review
- C-Type Natriuretic Peptide/Natriuretic Peptide Receptor 2 Is Involved in Cell Proliferation and Testosterone Production in Mouse Leydig Cells.The world journal of men's health · 2019Article
- SF-1 mediates reproductive toxicity induced by Cerium oxide nanoparticles in male mice.Journal of nanobiotechnology · 2019Article
- Corticosterone rather than ethanol epigenetic programmed testicular dysplasia caused by prenatal ethanol exposure in male offspring rats.Epigenetics · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic mutations of steroidogenic factor 1 (also known as Ad4BP or Nr5a1) have increasingly been reported in patients with 46,XY disorders of sex development (46,XY disorders of sex development). However, because the phenotype of 46,XY disorders of sex development with a steroidogenic factor 1 mutation is wide-ranging, its precise diagnosis remains a clinical problem. We previously reported the frequent occurrence of lipid accumulation in Leydig cells among patients with 46,XY disorders of sex development with a steroidogenic factor 1 mutation, an observation also reported by other authors. To address the mechanism of lipid accumulation in this disease, we examined the effects of steroidogenic factor 1 deficiency on downstream targets of steroidogenic factor 1 in in vitro and in vivo. We found that lipid accumulation in Leydig cells was enhanced after puberty in heterozygous steroidogenic factor 1 knockout mice compared with wild-type mice, and was accompanied by a significant decrease in steroidogenic acute regulatory protein and CYP11A1 expression. In mouse Leydig cell lines, steroidogenic factor 1 knockdown induced a remarkable accumulation of neutral lipids and cholesterol with reduced androgen levels. Steroidogenic factor 1 knockdown reduced the expression of steroidogenic acute regulatory protein and CYP11A1, both of which are transcriptional targets of steroidogenic factor 1 and key molecules for steroidogenesis from cholesterol in the mitochondria. Knockdown of either steroidogenic acute regulatory protein or CYP11A1 also induced lipid accumulation, and knockdown of both had an additive effect. Our data suggested that lipid accumulation in the Leydig cells of the 46,XY disorders of sex development phenotype with a steroidogenic factor 1 mutation is due, at least in part, to the suppression of steroidogenic acute regulatory protein and CYP11A1, and a resulting increase in unmetabolized cholesterol.
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