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Decrease in the Basal and Luteinizing Hormone Receptor Agonist–Stimulated Testosterone Production in Aging Male Rats

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Abstract

In the course of aging, the steroidogenic function of the testes weakens and their gonadotropin sensitivity decreases. However, the underlying mechanisms are poorly understood. The goal 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 production and the expression of steroidogenic proteins in young (3-month-old) and aging (15-month-old) male rats and to investigate the activity of the adenylyl cyclase system in the membranes isolated from the rat testes. Treatment with hCG (100 IU/rat/day) and TP03 (15 mg/kg/day) was carried out for 3 days. In the testes of aging rats, adenylyl cyclase stimulation 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 blood testosterone levels and the expression of the Star, Cyp11a1, and Cyp17a1 genes, which encode the StAR protein and the steroidogenic enzymes cytochromes P450scc and P450-17α in the testes, were decreased. The stimulating effect of both hCG and TP03 on testosterone production diminished with age, although their effects on LH/hCG receptor are mediated by different mechanisms. In both young and aging rats, hCG treatment upregulated the expression of the genes encoding StAR, P450scc and dehydrogenase 3β-HSD; at the same time, Hsd17B expression in aging rats increased, and the expression of the genes encoding P450-17α and 17β-HSD decreased in young rats. In young rats, TP03 treatment upregulated Star and Cyp17a1 expression, and it increased Star and Hsd17B expression in aging rats. Thus, in the testes of aging rats, the coupling between the LH/hCG receptor and Gs protein and LH/hCG receptor sensitivity to agonists were weakened, which led to a decrease in hCG- and TP03-induced testosterone production and altered the basal and LH/hCG receptor agonist–stimulated expression levels of some steroidogenic protein genes.

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ACKNOWLEDGMENTS

NMR, mass spectrometry, and radioisotopic studies were performed on the equipment of the resource centers of the St. Petersburg University Science Park: Magnetic Resonance-Based Methods and Methods of Composition Analysis, as well as the Collective Use Center of the Sechenov Institute.

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 16-04-00126) and partially supported by State Assignment AAAA-A18-118012290427-7.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    A. A. Bakhtyukov, K. V. Derkach, T. S. Sharova & A. O. Shpakov

  2. St. Petersburg State University, 199034, St. Petersburg, Russia

    D. V. Dar’in

Authors
  1. A. A. Bakhtyukov
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  2. K. V. Derkach
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  3. D. V. Dar’in
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  4. T. S. Sharova
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  5. A. O. Shpakov
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Correspondence to A. O. Shpakov.

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Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All procedures were performed in agreement with the requirements of the Ethical Committee of the Sechenov Institute, European Communities Council Directive 1986 (86/609/EEC), and the Guide for the Care and Use of Laboratory Animals.

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Translated by D. Timchenko

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Bakhtyukov, A.A., Derkach, K.V., Dar’in, D.V. et al. Decrease in the Basal and Luteinizing Hormone Receptor Agonist–Stimulated Testosterone Production in Aging Male Rats. Adv Gerontol 9, 179–185 (2019). https://doi.org/10.1134/S2079057019020036

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