Cyclic Nucleotide Phosphodiesterases (PDEs) Signaling in the Endocrine System

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Background

Second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are central players in numerous biological processes such as cell proliferation, energy metabolism, lipolysis, and hormone secretion. Intracellular levels of cAMP and cGMP are tightly maintained by cyclic nucleotide phosphodiesterases (PDEs), which are responsible for the hydrolysis of cyclic nucleotide pools in a temporal and spatial manner. PDEs are classified into eleven families, based on their specificity for cAMP or cGMP, structural similarity, and mechanism of regulation.

Mammalian PDEs are encoded by 21 genes that, following splicing processes, give rise to more than 100 different isoforms. A broad expression of PDEs in many cell types and its myriad functions in various aspect of cell biology have led to the development and characterization of PDE inhibitors. Several PDE inhibitors have been approved for the treatment of erectile dysfunction (ED), pulmonary arterial hypertension (PAH), and chronic obstructive pulmonary disease (COPD), as well as many others that are currently under clinical evaluation. PDEs play an important role in the regulation of hormone secretion and endocrine cell responses through their ability to regulate cyclic nucleotides; PDE inhibition represents a promising therapeutic approach for endocrine diseases. The complexity of cyclic nucleotides regulation in the endocrine system requires in-depth understanding of molecular and cellular mechanisms involved in PDEs signaling pathways.

This Research Topic aims to highlight the current understanding and recent advances of PDE signaling pathways in the physiology and pathophysiology of the endocrine system and to provide evidence on basic and translational research for the potential use of PDE inhibitors for the treatment of endocrine disorders. The primary focus of this issue is to enlighten our knowledge of PDE enzymes and their inhibition on the regulation of endocrine hormones and the metabolic and physiologic effects of PDEs over a broad range of tissues and organs, including the heart and lungs.

We particularly welcome high-quality Original Articles, Methods, Commentaries and Review Articles that fall under the following topics:

• Molecular mechanisms of PDEs signaling pathways in the physiology and pathophysiology of cardiovascular and endocrine systems;
• Function and characterization of PDE isoforms in cardiovascular and endocrine systems;
• Development and utilization of PDE inhibitors for the treatment of cardiovascular and endocrine disorders;
• Role of PDE and its inhibitors in the regulation of endocrine hormones and their metabolic effects on various organs including the heart, liver and lungs.

Keywords: cAMP, cGMP, PKA, PKG, Phosphodiesterase inhibitors, endocrine disorders, cell signaling, mouse models, metabolic disorders, cardiovascular diseases

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