ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 102 citations in OpenAlex.
- Androgen signaling is dispensable for fetal testis formation: decoupling testis organogenesis from fetal masculinization programming.Molecular human reproduction · 2026Review
- Evaluation and research progress on rodent models of late-onset hypogonadism: a comprehensive review.The Canadian journal of urology · 2025Review
- Collective cell dynamics and luminal fluid flow in the epididymis: A mechanobiological perspective.Andrology · 2024Review
- Inter- and trans-generational impacts of real-world PMCell discovery · 2024Article
- Adropin, a novel hepatokine: localization and expression during postnatal development and its impact on testicular functions of pre-pubertal mice.Cell and tissue research · 2024Article
- Article
- Associations of waist circumference with sex steroid hormones among 4031 USA children and adolescents.Asian journal of andrology · 2023Article
- Steroid hormone signaling: multifaceted support of testicular function.Frontiers in cell and developmental biology · 2023Review
- Revisiting the gonadotropic regulation of mammalian spermatogenesis: evolving lessons during the past decade.Frontiers in endocrinology · 2023Review
- A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function.International journal of molecular sciences · 2022Article
- Fancd2os Reduces Testosterone Production by Inhibiting Steroidogenic Enzymes and Promoting Cellular Apoptosis in Murine Testicular Leydig Cells.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Article
- Nuclear and Membrane Receptors for Sex Steroids Are Involved in the Regulation of Delta/Serrate/LAG-2 Proteins in Rodent Sertoli Cells.International journal of molecular sciences · 2022Article
- α-Tocopherol restores semen quality in rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.Veterinary world · 2022Article
- Emerging concepts on Leydig cell development in fetal and adult testis.Frontiers in endocrinology · 2022Review
- Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis.Frontiers in genetics · 2022Article
- Insights into the Regulation on Proliferation and Differentiation of Stem Leydig Cells.Stem cell reviews and reports · 2021Review
- Flutamide treatment reveals a relationship between steroidogenic activity of Leydig cells and ultrastructure of their mitochondria.Scientific reports · 2021Article
- Slit/Robo signaling regulates Leydig cell steroidogenesis.Cell communication and signaling : CCS · 2021Article
- A Testis-Specific Long Noncoding RNA,Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Leydig cell number and function decline as men age, and low testosterone is associated with all "Western" cardio-metabolic disorders. However, whether perturbed androgen action within the adult Leydig cell lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which androgen receptor (AR) is ablated from ∼75% of adult Leydig stem cell/cell progenitors, from fetal life onward (Leydig cell AR knockout mice), permitting interrogation of the specific roles of autocrine Leydig cell AR signaling through comparison to adjacent AR-retaining Leydig cells, testes from littermate controls, and to human testes, including from patients with complete androgen insensitivity syndrome (CAIS). This revealed that autocrine AR signaling is dispensable for the attainment of final Leydig cell number but is essential for Leydig cell maturation and regulation of steroidogenic enzymes in adulthood. Furthermore, these studies reveal that autocrine AR signaling in Leydig cells protects against late-onset degeneration of the seminiferous epithelium in mice and inhibits Leydig cell apoptosis in both adult mice and patients with CAIS, possibly via opposing aberrant estrogen signaling. We conclude that autocrine androgen action within Leydig cells is essential for the lifelong support of spermatogenesis and the development and lifelong health of Leydig cells.
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