Phosphodiesterases in endocrine physiology and disease

Vezzosi, Delphine; Bertherat, Jérôme

doi:10.1530/eje-10-1123

Cited by 34 publications

(28 citation statements)

References 103 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The phosphodiesterase encoded by PDE5A is substantially expressed in the testis, and mice overexposed to inhibitors of this protein present testicular tissue alterations, including decreased testis weight, degeneration, and atrophy of the seminiferous epithelium [32]. This genomic region also shelters genes that interact with other proteins previously linked to small testis size.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Mapping of Loci Explaining Variance in Scrotal Circumference in Nellore Cattle

et al. 2014

View full text Add to dashboard Cite

The reproductive performance of bulls has a high impact on the beef cattle industry. Scrotal circumference (SC) is the most recorded reproductive trait in beef herds, and is used as a major selection criterion to improve precocity and fertility. The characterization of genomic regions affecting SC can contribute to the identification of diagnostic markers for reproductive performance and uncover molecular mechanisms underlying complex aspects of bovine reproductive biology. In this paper, we report a genome-wide scan for chromosome segments explaining differences in SC, using data of 861 Nellore bulls (Bos indicus) genotyped for over 777,000 single nucleotide polymorphisms. Loci that excel from the genome background were identified on chromosomes 4, 6, 7, 10, 14, 18 and 21. The majority of these regions were previously found to be associated with reproductive and body size traits in cattle. The signal on chromosome 14 replicates the pleiotropic quantitative trait locus encompassing PLAG1 that affects male fertility in cattle and stature in several species. Based on intensive literature mining, SP4, MAGEL2, SH3RF2, PDE5A and SNAI2 are proposed as novel candidate genes for SC, as they affect growth and testicular size in other animal models. These findings contribute to linking reproductive phenotypes to gene functions, and may offer new insights on the molecular biology of male fertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-Wide Mapping of Loci Explaining Variance in Scrotal Circumference in Nellore Cattle

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Phosphodiesterases exist in over 100 isoforms and are derived from 21 genes separated into 11 PDE gene families (summarized in Table 1) (8–10). PDEs function through the hydrolyzation of cAMP (PDEs isoform 4, 7, and 8) and cyclic guanosine monophosphate (cGMP) (PDEs isoforms 5, 6, and 9) into AMP and GMP, respectively (8, 9).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Phosphodiesterases in Adrenocortical Tumors

2016

View full text Add to dashboard Cite

Alterations in the cyclic (c)AMP-dependent signaling pathway have been implicated in the majority of benign adrenocortical tumors (ACTs) causing Cushing syndrome (CS). Phosphodiesterases (PDEs) are enzymes that regulate cyclic nucleotide levels, including cyclic adenosine monophosphate (cAMP). Inactivating mutations and other functional variants in PDE11A and PDE8B, two cAMP-binding PDEs, predispose to ACTs. The involvement of these two genes in ACTs was initially revealed by a genome-wide association study in patients with micronodular bilateral adrenocortical hyperplasia. Thereafter, PDE11A or PDE8B genetic variants have been found in other ACTs, including macronodular adrenocortical hyperplasias and cortisol-producing adenomas. In addition, downregulation of PDE11A expression and inactivating variants of the gene have been found in hereditary and sporadic testicular germ cell tumors, as well as in prostatic cancer. PDEs confer an increased risk of ACT formation probably through, primarily, their action on cAMP levels, but other actions might be possible. In this report, we review what is known to date about PDE11A and PDE8B and their involvement in the predisposition to ACTs.

show abstract

“…P hosphodiesterase (PDEs) enzymes have an important role in regulation of signaling pathways that are involved in the pathophysiology of polycystic ovary syndrome (PCOS) (1,2). They modulate steroidogenesis and complex responses to proinflammatory and metabolic mediators in ovaries (1,3).…”

mentioning

confidence: 99%

“…They modulate steroidogenesis and complex responses to proinflammatory and metabolic mediators in ovaries (1,3). From a conceptual point of view, there are several reasons to imply the pharmacological inhibition of PDEs as a potential new multimodal target in this endocrine disorder.…”

mentioning

confidence: 99%