ArticleMolecular endocrinology (Baltimore, Md.)2011
The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 74 citations in OpenAlex.
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- Platelet-derived growth factor receptor alpha regulates fetal testis differentiation via an ERK-CREB axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Role of p38 MAPK Signalling in Testis Development and Male Fertility.Oxidative medicine and cellular longevity · 2022Review
- DAPL1 is a novel regulator of testosterone production in Leydig cells of mouse testis.Scientific reports · 2021Article
- Advances in stem cell research for the treatment of primary hypogonadism.Nature reviews. Urology · 2021Review
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- Erdheim-Chester disease with concomitant Rosai-Dorfman like lesions: a distinct entity mainly driven byHaematologica · 2020Article
- Brain-derived neurotrophic factor: A steroidogenic regulator of Leydig cells.Journal of cellular physiology · 2019Article
- Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.Reproductive biology and endocrinology : RB&E · 2017Article
- Neuregulin 1 Regulates Proliferation of Leydig Cells to Support Spermatogenesis and Sexual Behavior in Adult Mice.Endocrinology · 2016Article
- Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function.Frontiers in endocrinology · 2016Review
- Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells.Biology of reproduction · 2015Article
- Genetic Models for the Study of Luteinizing Hormone Receptor Function.Frontiers in endocrinology · 2015Review
- Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients.Journal of neural transmission (Vienna, Austria : 1996) · 2015Article
- The stage-specific testicular germ cell apoptotic response to low-dose X-irradiation and 2,5-hexanedione combined exposure. I: Validation of the laser capture microdissection method for qRT-PCR array application.Toxicologic pathology · 2014Article
- Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats.Journal of Zhejiang University. Science. B · 2014Article
- New insights into the genetic basis of infertility.The application of clinical genetics · 2014Review
- Precocious puberty and Leydig cell hyperplasia in male mice with a gain of function mutation in the LH receptor gene.Endocrinology · 2013Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
MAPK kinase (MEK)1 and MEK2 were deleted from Leydig cells by crossing Mek1(f/f);Mek2(-/-) and Cyp17iCre mice. Primary cultures of Leydig cell from mice of the appropriate genotype (Mek1(f/f);Mek2(-/-);iCre(+)) show decreased, but still detectable, MEK1 expression and decreased or absent ERK1/2 phosphorylation when stimulated with epidermal growth factor, Kit ligand, cAMP, or human choriogonadotropin (hCG). The body or testicular weights of Mek1(f/f);Mek2(-/-);iCre(+) mice are not significantly affected, but the testis have fewer Leydig cells. The Leydig cell hypoplasia is paralleled by decreased testicular expression of several Leydig cell markers, such as the lutropin receptor, steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, 17α-hydroxylase, and estrogen sulfotransferase. The expression of Sertoli or germ cell markers, as well as the shape, size, and cellular composition of the seminiferous tubules, are not affected. cAMP accumulation in response to hCG stimulation in primary cultures of Leydig cells from Mek1(f/f);Mek2(-/-);iCre(+) mice is normal, but basal testosterone and testosterone syntheses provoked by addition of hCG or a cAMP analog, or by addition of substrates such as 22-hydroxycholesterol or pregnenolone, are barely detectable. The Mek1(f/f);Mek2(-/-);iCre(+) males show decreased intratesticular testosterone and display several signs of hypoandrogenemia, such as elevated serum LH, decreased expression of two renal androgen-responsive genes, and decreased seminal vesicle weight. Also, in spite of normal sperm number and motility, the Mek1(f/f);Mek2(-/-);iCre(+) mice show reduced fertility. These studies show that deletion of MEK1/2 in Leydig cells results in Leydig cell hypoplasia, hypoandrogenemia, and reduced fertility.
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