ArticleProceedings of the National Academy of Sciences of the United States of America2006
Modulation of Leydig cell function by cyclic nucleotide phosphodiesterase 8A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 91 citations in OpenAlex.
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- C2orf74 orchestrates germ-Leydig crosstalk to inhibit white adipose tissue browning in male mice.Nature communications · 2026Article
- Roles of Cyclic Nucleotide Phosphodiesterases in Signal Transduction Pathways in the NematodeCells · 2025Review
- Luteinizing Hormone Regulates Testosterone Production, Leydig Cell Proliferation, Differentiation, and Circadian Rhythm During Spermatogenesis.International journal of molecular sciences · 2025Review
- Evolutionary innovations in germline biology of placental mammals identified by transcriptomics of first-wave spermatogenesis in opossum.Developmental cell · 2025Article
- Review
- Article
- Protective effect of gomisin N on benzyl butyl phthalate-induced dysfunction of testosterone production in TM3 Leydig cells.Molecular biology reports · 2024Article
- Effects of intracerebroventricular administration of calcitonin gene-related peptide (CGRP) on sex hormones and sperm quality in rats.Annals of medicine and surgery (2012) · 2023Article
- Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.International journal of molecular sciences · 2023Review
- Circulating microRNAs as promising testicular translatable safety biomarkers: current state and future perspectives.Archives of toxicology · 2023Review
- Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Prognostic and Clinical Implications of UNC13C expression in Hepatocellular Carcinoma Patients.International journal of medical sciences · 2023Article
- Leptin secreted from testicular microenvironment modulates hedgehog signaling to augment the endogenous function of Leydig cells.Cell death & disease · 2022Article
- cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor.Frontiers in endocrinology · 2022Article
- Analysis of spermatogenesis and fertility in adult mice with a hypomorphic mutation in the Mtrr gene.Reproduction, fertility, and development · 2019Article
- Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells.Scientific reports · 2019Article
- Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications.Frontiers in endocrinology · 2019Review
- PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by βAmerican journal of respiratory cell and molecular biology · 2018Article
- Phosphodiesterase type 5 and cancers: progress and challenges.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Leydig cells produce testosterone in the testes under the pulsatile control of pituitary luteinizing hormone (LH). cAMP is the intracellular messenger for LH action on steroidogenesis, and pharmacological evidence indicates that the response to LH can be modulated by cyclic nucleotide phosphodiesterases (PDEs). However the types and roles of the PDEs present in Leydig cells have not been fully defined. We report here that PDE8A is expressed in Leydig cells, and using PDE8A knockout mice we provide evidence that PDE8A is a key regulator of LH signaling and steroidogenesis. A 4-fold increase in the sensitivity to LH for testosterone production was detected in Leydig cells isolated from PDE8A knockout mice. In Leydig cells from wild-type mice, 3-isobutyl-1-methylxanthine, a compound that inhibits all cAMP PDEs except PDE8A, elicited only a small increase in the sensitivity of testosterone production to LH. However, in the PDE8-null mice, the effect of this inhibitor is much more pronounced. These observations indicate that PDE8A and at least one other PDE control the same or a complementary pool of cAMP that mediates LH-regulated steroidogenesis. Overall, these results suggest that pharmacological manipulation of PDE8A, alone or in combination with other PDEs present in Leydig cells, may be exploited to modulate testosterone synthesis and possibly to treat various conditions where the local levels of this androgen need to be altered.
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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.