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Rôle du peptide vasoactif intestinal (VIP) dans la stéroïdogenèse et le vieillissement testiculaire

Role of vasoactive intestinal peptide (VIP) in steroidogenesis and aging in mouse testis

Resume

Des travauxin vitro suggèrent que le VIP pourrait jouer un rôle important au niveau de la biosynthèse de testostérone. Nous avons démontré que des Souris chez lesquelles le gène codant pour le VIP est supprimé montrent des niveaux de testostérone sériques très réduits comparés aux animaux sauvages. Egalement, ces animaux transgéniques présentent une réduction des niveaux de FSH (Follicle-stimulating hormone) à l’âge de quatre mois.

L’étude de la structure testiculaire a révélé une légère augmentation du pourcentage de tubules dégénérés chez les animaux VIP-/-comparés aux animaux sauvages. Les animaux chez lesquels le gène codant pour le VIP a été supprimé, à l’âge de quinze mois, ont des niveaux de stéroïdogenèse bas comparés aux souris sauvages. De manière intéressante, la dégénérescence testiculaire est moins sévère chez les animaux VIP-/-comparée à celles des animaux sauvages.

L’ensemble de ces résultats suggère que: 1) le VIP est un facteur important pour la régulation de la biosynthèse de testostérone et la sécrétion de FSH et 2) VIP régule le vieillissement testiculaire.

Abstract

VIP (vasoactive intestinal peptide) neuropeptide has long been considered to be putative regulator of testicular functions.In vitro evidence suggests that VIP could play an important role in testosterone biosynthesis. However, the endogenous role of VIP on testicular functions remained to be demonstrated.

In C57BL/6 mice exhibiting complete disruption of the VIP gene, the authors observed that male fertility remained intact but serum testosterone levels were lower than those of WT littermates. At the age of 4 months, this phenotype was accompanied by reduced steroidogenesis due to inhibition of the expression of StAR (steroidogenic acute regulatory protein) and 3ßHSD (3ß-hydroxysteroid dehydrogenase) in the testis. In addition, serum levels of FSH (Follicle-stimulating hormone) but not LH (Luteinizing hormone) were reduced in young KO males. Testicular anatomy also revealed a subtle but significantly higher percentage of degenerated seminiferous tubules in 4-month-old VIP-/-animals compared to WT.

In aging animals (15 months old), control males showed typical testicular aging including severe degeneration of seminiferous tubules, a dramatic decrease in serum testosterone levels and a reduction in StAR and 3ß-HSD gene expression. In age-matched VIP-/-males, serum levels of testosterone and steroidogenic enzymes were still very low. Interestingly, in contrast with young mice, testicular degeneration at 15 months was significantly less severe marked in VIP-/-mice than in WT mice. Altogether, these results suggest that: 1) VIP is an important factor for regulating testosterone biosynthesis and FSH secretion and 2) VIP regulates testicular aging.

Références

  1. BRENNEMAN D.E., GLAZNER G., HILL J.M., HAUSER J., DAVIDSON A., GOZES I.: VIP neurotrophism in the central nervous system: multiple effectors and identification of a femtomolar-acting neuroprotective peptide. Ann. N.Y. Acad. Sci., 1998, 865: 207–212.

    Article  PubMed  CAS  Google Scholar 

  2. EL-GEHANI F., TENA-SEMPERE M., HUHTANIEMI I.: Vasoactive intestinal peptide stimulates testosterone production by cultured fetal rat testicular cells. Mol. Cell. Endocrinol., 1998, 140: 175–178.

    Article  PubMed  CAS  Google Scholar 

  3. KASSON B.G., LIM P., HSUEH A.J.: Vasoactive intestinal peptide stimulates androgen biosynthesis by cultured neonatal testicular cells. Mol. Cell. Endocrinol., 1986, 48: 21–29.

    Article  PubMed  CAS  Google Scholar 

  4. KOVES K., GOTTSCHALL P.E., GORCS T., SCAMMELL J.G., ARIMURA A.: Presence of immunoreactive vasoactive intestinal polypeptide in anterior pituitary of normal male and long term estrogen-treated female rats: a light microscopic immunohistochemical study. Endocrinology, 1990, 126: 1756–1763.

    Article  PubMed  CAS  Google Scholar 

  5. LAM K.S.: Vasoactive intestinal peptide in the hypothalamus and pituitary. Neuroendocrinology, 1991, 53 Suppl 1:45–51.

    Article  PubMed  CAS  Google Scholar 

  6. LOREN I., EMSON P.C., FAHRENKRUG J. et al.: Distribution of vasoactive intestinal polypeptide in the rat and mouse brain. Neuroscience, 1979, 4: 1953–1976.

    Article  PubMed  CAS  Google Scholar 

  7. MULLER J.M., LELIEVRE V., BECQ-GIRAUDON L., MEUNIER A.C.: VIP as a cell-growth and differentiation neuromodulator role in neurodevelopment. Mol. Neurobiol., 1995, 10: 115–134.

    Article  PubMed  CAS  Google Scholar 

  8. NAGY G., MULCHAHEY J.J., NEILL J.D.: Autocrine control of prolactin secretion by vasoactive intestinal peptide. Endocrinology, 1988, 122: 364–366.

    PubMed  CAS  Google Scholar 

  9. RESKO J.A., MALLEY A., BEGLEY D., HESS D.L.: Radioimmunoassay of testosterone during fetal development of the rhesus monkey. Endocrinology, 1973, 93: 156–161.

    PubMed  CAS  Google Scholar 

  10. SAID S.I., MUTT V.: Polypeptide with broad biological activity: isolation from small intestine. Science, 1970, 169: 1217–1218.

    Article  PubMed  CAS  Google Scholar 

  11. SAID S.I., ROSENBERG R.N.: Vasoactive intestinal polypeptide: abundant immunoreactivity in neural cell lines and normal nervous tissue. Science, 1976, 192: 907–908.

    Article  PubMed  CAS  Google Scholar 

  12. SIMONI M., WEINBAUER G.F., GROMOLL J., NIESCHLAG E.: Role of FSH in male gonadal function. Ann. Endocrinol. (Paris), 1999, 60: 102–106.

    CAS  Google Scholar 

  13. SUH J.K., MUN K.H., CHO C.K., SHIN H.C., KIM Y.S., PARK T.C.: Effect of vasoactive intestinal peptide and acetylcholine on penile erection in the rat in vivo. Int. J. Impôt. Res., 1995, 7: 111–118.

    PubMed  CAS  Google Scholar 

  14. WASCHEK J.A.: Vasoactive intestinal peptide: an important trophic factor and developmental regulator? Dev. Neurosci., 1995, 17: 1–7.

    Article  PubMed  CAS  Google Scholar 

  15. ZHANG F.P., PAKARAINEN T., POUTANEN M., TOPPARI J., HUHTANIEMI I.: The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis. Proc. Natl. Acad. Sci. USA, 2003, 100: 13692–13697.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Eric Vilain.

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Lacombe, A., Lelievre, V., Roselli, C.E. et al. Rôle du peptide vasoactif intestinal (VIP) dans la stéroïdogenèse et le vieillissement testiculaire. Androl. 17, 123–128 (2007). https://doi.org/10.1007/BF03041165

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