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The aging leads to a weakening of the steroid function of the testes and a decrease in their sensitivity to gonadotropins. However, the mechanisms of this are poorly understood. The aim of this work was to study the stimulating effects of human chorionic gonadotropin (hCG) and TP03, a low-molecular-weight agonist of luteinizing hormone (LH)/hCG receptor, on testosterone (T) production and the expression of steroidogenic proteins in young (3 months) and aging (15 months) male rats, and to investigate the activity of the adenylyl cyclase system in the membranes isolated from the testes of rats. The treatment with hCG (100 IU/rat/day) and TP03 (15 mg/rat/day) was carried out for 3 days. In the testes of aging rats the stimulation of adenylyl cyclase (AC) by gonadotropin and guanine nucleotide was decreased, indicating a weakening of the coupling of LH/hCG receptor and Gs protein, the main components of the adenylyl cyclase system regulating the steroidogenesis. In elderly rats, the T level in the blood and the expression of the Star, Cyp11a1 and Cyp17a1 genes encoding the StAR protein and the steroidogenic enzymes cytochromes P450scc and P450-17α in the testes were decreased. With increasing age, the stimulating effect of hCG and TP03 on the T production was weakened, despite the different mechanisms of their action on LH/hCG receptor. The treatment of both young and aging rats with hCG led to an increase in the expression of the genes encoding StAR, P450scc and dehydrogenase 3β-HSD, while in aging rats, in addition, the expression of the Hsd17B gene was increased and in young rats the expression of the genes encoding Р450-17α and 17β-HSD was reduced. The treatment of in young rats with TP03 led to an increase in the Star and Cyp17a1 expression, and the TP03 treatment of aging rats increased the Star and Hsd17B expression. Thus, in the testes of aging rats, the coupling between LH/hCG receptor and Gs-protein and the sensitivity of LH/hCG receptor to agonists were weakened, which leads to a decrease in the hCG- and TP03-induced production of T, and the basal and LH/hCG receptor agonists-stimulated levels of gene expression for some steroidogenic proteins were changed.
| Original language | Russian |
|---|---|
| Pages (from-to) | 654-661 |
| Number of pages | 8 |
| Journal | Advances in gerontology = Uspekhi gerontologii |
| Volume | 31 |
| Issue number | 5 |
| State | Published - 1 Jan 2018 |
ID: 51317926