The second messenger, cAMP, is one of the most important regulatory signals for control of steroidogenesis. This review focuses on current knowledge about regulation of cyclic nucleotides by phosphodiesterases (PDEs) in steroidogenic tissues. The first PDE known to directly regulate steroidogenesis was PDE2, the cGMP-stimulated PDE. PDE2 mediates ANP/cGMP-induced decreases in aldosterone production. Recently, the PDE8 family has been shown to control steroidogenesis in two tissues. Specifically, PDE8A regulates testosterone production by itself and in concert with additional IBMX-sensitive PDEs. PDE8B modulates basal corticosterone synthesis via acute and chronic mechanisms. In addition to cAMP-dependent pathways, cGMP signaling also can promote steroidogenesis, and PDE5 modulates this process. Finally, PDE mutations may lead to several human diseases characterized by abnormal steroid levels.
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http://dx.doi.org/10.1016/j.coph.2011.09.003 | DOI Listing |
Cells
January 2025
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Phosphodiesterases, particularly the type 5 isoform (PDE5), have gained recognition as pivotal regulators of male reproductive physiology, exerting significant influence on testicular function, sperm maturation, and overall fertility potential. Over the past several decades, investigations have expanded beyond the original therapeutic intent of PDE5 inhibitors for erectile dysfunction, exploring their broader reproductive implications. This narrative review integrates current evidence from in vitro studies, animal models, and clinical research to clarify the roles of PDEs in effecting the male reproductive tract, with an emphasis on the mechanistic pathways underlying cyclic nucleotide signaling, the cellular specificity of PDE isoform expression, and the effects of PDE5 inhibitors on Leydig and Sertoli cell functions.
View Article and Find Full Text PDFClin Psychopharmacol Neurosci
February 2025
Department of Mental Health of Enna, Psychiatry Unity, Enna Hospital, Enna, Italy.
Intracellular cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate) and downstream cellular signal transduction are regulated by phosphodiesterases (PDEs). The neuroplasticity, neurotransmitter pathways, and neuroinflammation-controlling functions of PDEs were demonstrated in numerous in vitro and animal model studies. We comprehensively reviewed the literature regarding the expression of PDEs in various brain regions.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Chemical Research Laboratories, i2i-Labo, Biological Pharmacological Research Laboratories, and Drug Metabolism & Pharma-cokinetics Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco, Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
Phosphodiesterases (PDEs) have drawn attention due to their critical roles in physiological and pathological conditions. Many research groups have studied these hydrolytic enzymes to develop new drugs, including apremilast as a PDE4 inhibitor and sildenafil as a PDE5 inhibitor. Targeting PDE7 has also been deemed a rational strategy to ameliorate autoimmune conditions.
View Article and Find Full Text PDFInflammopharmacology
January 2025
Department of Pharmacology, Central University of Punjab, Bathinda, 151001, Punjab, India.
Alzheimer's Disease (AD), a progressive and age-associated neurodegenerative disorder, is primarily characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. Despite advances in targeting Aβ-mediated neuronal damage with anti-Aβ antibodies, these treatments provide only symptomatic relief and fail to address the multifactorial pathology of the disease. This necessitates the exploration of novel therapeutic approaches and a deeper understanding of molecular signaling mechanisms underlying AD.
View Article and Find Full Text PDFComput Biol Chem
December 2024
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:
Due to the unclear selectivity of the protein system, designing selective small molecule inhibitors has been a significant challenge. This issue is particularly prominent in the phosphodiesterases (PDEs) system. Phosphodiesterase 1B (PDE1B) and phosphodiesterase 10 A (PDE10A) are two closely related subtypes of PDE proteins that play diverse roles in the immune system and tumorigenesis, respectively.
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