Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Sokanovic 2013 Endocrinology

From Bioblast
Publications in the MiPMap
Sokanovic SJ, Baburski AZ, Janjic MM, Stojkov NJ, Bjelic MM, Lalosevic D, Andric SA, Stojilkovic SS, Kostic TS (2013) The opposing roles of nitric oxide and cGMP in the age-associated decline in rat testicular steroidogenesis. Endocrinology 154:3914–24.

Β» PMID: PMC3776867 Open Acces

Sokanovic SJ, Baburski AZ, Janjic MM, Stojkov NJ, Bjelic MM, Lalosevic D, Andric SA, Stojilkovic SS, Kostic TS (2013) Endocrinology

Abstract: The molecular mechanism of the aging-associated dysfunction of Leydig cells (LCs) is complex and poorly understood. In this study, we analyzed the contribution of nitric oxide (NO) and cGMP signaling to the age-dependent decline in LC function. Significant (>50%) decreases in serum, intratesticular, and LC androgens in aging rats (15–24 months) were accompanied by a proportional increase in NO production, an up-regulation of cGMP levels, and the expression of soluble guanylyl cyclase-1B and protein kinase G1 in LCs. In contrast, LC cAMP levels decreased with age, most likely reflecting the up-regulation of cAMP-specific phosphodiesterase expression. Moreover, the expression of genes encoding enzymes responsible for cholesterol transport and its conversion to T were reduced. Exposing LCs from aged animals to NO further increased cGMP levels and decreased cAMP and androgen production, whereas the addition of cell-permeable 8-bromoguanosine-cGMP alone had the opposite effect. In vivo inhibition of cGMP-specific phosphodiesterase-5 for 3 and 6 months in aged rats led to a partial restoration of androgens, NO, and cyclic nucleotide levels, as well as the expression of steroidogenic and NO/cGMP signaling genes. These results indicate that a progressive increase in NO production contributes to the age-dependent decrease in steroidogenesis in a cGMP-independent manner, whereas the sustained elevation in cGMP levels significantly slows the decline in LC function.


Labels: Pathology: Aging;senescence 

Organism: Rat  Tissue;cell: Genital