Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells

Baburski, Aleksandar Z.; Sokanovic, Srdjan J.; Andrić, Silvana A.; Kostic, Tatjana S.

doi:10.1007/s00360-016-1052-7

Cited by 13 publications

(7 citation statements)

References 49 publications

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“…In the same study, Authors, considering the pronounced androgen dependency of prostate, investigated the expression of cGMP pathway proteins in this tissue in conditions of androgen deprivation. Interestingly, they showed a further upregulation of PKG1 and a less pronounced increase in PDE5 expression (42), similarly to what Baburski et al showed in LCs of aged rats (34). At the prostate level, the cGMP pathway could be implicated in the relaxing activity and in the regulation of proliferation and differentiation of smooth muscle cells.…”

Section: Age-related Changes In T Production and Pde Expression In Thsupporting

confidence: 71%

“…In fact, the up-regulation of the PDE5 gene by T would create a paradox in which a positive regulator of erectile function (androgen) would increase the level of a negative regulator (PDE5), potentially leading to worsening of ED and to a more difficult clinical management (39). Moreover, if so, in the corpora cavernosa would occur the exact opposite of what happens in LCs, where aging-related T decrease is associated to an increased expression of PDE5 (34). Finally, two studies that have looked for androgen-responsive genes in the whole human genome and they found respectively 524 and 1,532 potential AR-binding sites, but PDE5A gene was not among them (40, 41).…”

Section: Age-related Changes In T Production and Pde Expression In Thmentioning

confidence: 98%

“…Aged animals not only have significantly lower T concentration than adults but they also loose the normal T secretion rhythmicity (31). In LCs of aged rats, the alteration also occurs in the transcription rhythmicity of genes involved in both cAMP and cGMP pathways (34). Aging has been suggested to strengthen the negative cross-talk between the two signaling pathways through changes in the expression of PDEs with dual activity, but these data have to be confirmed (34).…”

Section: Age-related Changes In T Production and Pde Expression In Thmentioning

confidence: 99%

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Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

et al. 2019

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The age-related decline of serum T occurs in ~20–30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

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Section: Age-related Changes In T Production and Pde Expression In Thsupporting

confidence: 71%

Section: Age-related Changes In T Production and Pde Expression In Thmentioning

confidence: 98%

Section: Age-related Changes In T Production and Pde Expression In Thmentioning

confidence: 99%

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Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

et al. 2019

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“…ADCY9 protein is affected by changes in membrane-rich cholesterol plasma membrane domains (Niesor and Benghozi, 2015). Reduced amplitude of cAMP circadian oscillation was probably associated with changed expression of ADCY9 (Baburski et al, 2017). ITGA1 and ADCY9 competed for binding to miR-181b, and ZEB1 upregulated ITGA1 to activate a miR-181b-regulated ceRNA network that increased metastasis through ADCY9 (Tan et al, 2018) in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

Jia

Xie

et al. 2021

Front. Genet.

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BackgroundLung cancer is the tumor with the highest morbidity and mortality, and has become a global public health problem. The incidence of lung cancer in men has declined in some countries and regions, while the incidence of lung cancer in women has been slowly increasing. Therefore, the aim is to explore whether estrogen-related genes are associated with the incidence and prognosis of lung cancer.MethodsWe obtained all estrogen receptor genes and estrogen signaling pathway genes in The Cancer Genome Atlas (TCGA), and then compared the expression of each gene in tumor tissues and adjacent normal tissues for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) separately. Survival analysis was performed of the differentially expressed genes in LUAD and LUSC patients separately. The diagnostic and prognostic values of the candidate genes were validated in the Gene Expression Omnibus (GEO) datasets.ResultsWe found 5 estrogen receptor genes and 66 estrogen pathway genes in TCGA. A total of 50 genes were differently expressed between tumor tissues and adjacent normal tissues and 6 of the 50 genes were related to the prognosis of LUAD in TCGA. 56 genes were differently expressed between tumor tissues and adjacent normal tissues and none of the 56 genes was related to the prognosis of LUSC in TCGA. GEO datasets validated that the 6 genes (SHC1, FKBP4, NRAS, PRKCD, KRAS, ADCY9) had different expression between tumor tissues and adjacent normal tissues in LUAD, and 3 genes (FKBP4, KRAS, ADCY9) were related to the prognosis of LUAD.ConclusionsThe expressions of FKBP4 and ADCY9 are related to the pathogenesis and prognosis of LUAD. FKBP4 and ADCY9 may serve as biomarkers in LUAD screening and prognosis prediction in clinical settings.

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“…Interestingly, pharmacological stimulation of PKG, a downstream signaling molecule of sGC-cGMP, actually have effects on ECs, VSMCs and platelets. It reduces neointimal hyperplasia, inhibits platelet aggregation, and facilitates re- endothelialization ( 74 ).…”

Section: Functions Of Rnf213 and Sgc In The Vascular Wall And Circulationmentioning

confidence: 99%

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

Mineharu

Miyamoto

2021

Front. Neurol.

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Moyamoya disease is an idiopathic chronically progressive cerebrovascular disease, which causes both ischemic and hemorrhagic stroke. Genetic studies identified RNF213/Mysterin and GUCY1A3 as disease-causing genes. They were also known to be associated with non-moyamoya intracranial large artery disease, coronary artery disease and pulmonary artery hypertension. This review focused on these two molecules and their strong linker, calcineurin/NFAT signaling and caveolin to understand the pathophysiology of moyamoya disease and related vascular diseases. They are important regulators of lipid metabolism especially lipotoxicity, NF-κB mediated inflammation, and nitric oxide-mediated vascular protection. Although intimal thickening with fibrosis and damaged vascular smooth muscle cells are the distinguishing features of moyamoya disease, origin of the fibrous tissue and the mechanism of smooth muscle cell damages remains not fully elucidated. Endothelial cells and smooth muscle cells have long been a focus of interest, but other vascular components such as immune cells and extracellular matrix also need to be investigated in future studies. Molecular research on moyamoya disease would give us a clue to understand the mechanism preserving vascular stability.

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Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells

Cited by 13 publications

References 49 publications

Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

Transcriptome Based Estrogen Related Genes Biomarkers for Diagnosis and Prognosis in Non-small Cell Lung Cancer

RNF213 and GUCY1A3 in Moyamoya Disease: Key Regulators of Metabolism, Inflammation, and Vascular Stability

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