ArticleProceedings of the National Academy of Sciences of the United States of America2004
Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 196 citations in OpenAlex.
- Androgen rapidly activates phosphorylation signaling pathways in Sertoli cells.Experimental and therapeutic medicine · 2026Article
- Multi-omic analysis of androgen-deprived human testes reveals Sertoli cell regulation and niche reprogramming.Nature communications · 2026Article
- Understanding the Secular Decline in Testosterone: Mechanisms, Consequences, and Clinical Perspectives.International journal of molecular sciences · 2026Review
- Article
- Hormone Regulation in Testicular Development and Function.International journal of molecular sciences · 2024Review
- Caffeine attenuates spermatogenic disorders in mice with induced chronic scrotal hyperthermia.Clinical and experimental reproductive medicine · 2024Article
- Sex-dependent regulation of mucin gene transcription and airway secretion and mechanics following intra-airway IL-13 in mice with conditional loss of club cell Creb1.Frontiers in physiology · 2024Article
- Steroid receptors in the testis: implications in the physiology of prenatal and postnatal development and translation to clinical application.Histology and histopathology · 2023Review
- Co-Culture of Cryopreserved Healthy Sertoli Cells with Testicular Tissue of Non-Obstructive Azoospermia (NOA) Patients in Culture Media Containing Follicle-Stimulating Hormone (FSH)/Testosterone Has No Advantage in Germ Cell Maturation.Journal of clinical medicine · 2023Article
- Male Sex Hormones, Metabolic Syndrome, and Aquaporins: A Triad of Players in Male (in)Fertility.International journal of molecular sciences · 2023Review
- Steroid hormone signaling: multifaceted support of testicular function.Frontiers in cell and developmental biology · 2023Review
- It puts the T's in fertility: testosterone and spermatogenesis.International journal of impotence research · 2022Review
- What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?Frontiers in endocrinology · 2022Review
- GnRH pulse frequency and irregularity play a role in male aging.Nature aging · 2021Article
- Mediterranean Pine Vole,Animals : an open access journal from MDPI · 2021Article
- Androgen Effects on Neural Plasticity.Androgens: clinical research and therapeutics · 2021Review
- Androgen Actions in the Testis and the Regulation of Spermatogenesis.Advances in experimental medicine and biology · 2021Review
- The Molecular Mechanism of Sex Hormones on Sertoli Cell Development and Proliferation.Frontiers in endocrinology · 2021Review
- The Implication of Androgens in the Presence of Protein Kinase C to Repair Alzheimer’s Disease-Induced Cognitive DysfunctionIranian biomedical journal · 2020Review
- Signatures of sex: Sex differences in gene expression in the vertebrate brain.Wiley interdisciplinary reviews. Developmental biology · 2020Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The androgen testosterone is essential for the Sertoli cell to support the maturation of male germ cells and the production of spermatozoa (spermatogenesis). In the classical view of androgen action, binding of androgen to the intracellular androgen receptor (AR) produces a conformational change in AR such that the receptor-steroid complex has high affinity for specific DNA regulatory elements and is able to stimulate gene transcription. Here, we demonstrate that testosterone can act by means of an alternative, rapid, and sustainable mechanism in Sertoli cells that is independent of AR-DNA interactions. Specifically, the addition of physiological levels of testosterone to Sertoli cells stimulates the mitogen-activated protein kinase signaling pathway and causes phosphorylation of the cAMP response element binding protein transcription factor on serine 133, a modification known to be required for Sertoli cells to support spermatogenesis. Androgen-mediated activation of mitogen-activated protein kinase and cAMP response element binding protein occurs within 1 min, extends for at least 12 h and requires AR. Furthermore, androgen induces endogenous cAMP response element binding protein-mediated transcription in Sertoli cells. These newly identified mechanisms of androgen action in Sertoli cells suggest new targets for developing male contraceptive agents.
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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.