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Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats

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Abstract

We investigated the impact of dietary restriction on the basal rate of somatotrope renewal in the pituitary gland. Bromodeoxyuridine (BrdU), a thymidine analog, was administered continuously for 1 week in male F344 rats at 3, 8 and 20 months of age (mo), fed ad libitum (AL) or diet restricted from 1.5 mo (DR). Combined immunostainings for BrdU and GH visualized newly formed somatotropes as well as pituitary cells in tissue sections. The rate of incorporation of BrdU by anterior pituitary cells (BrdU-labeled nuclei/100 nuclei) was not influenced by the dietary regimen or age. The fraction of BrdU-labeled somatotropes relative to all labeled cells precipitously decreased to the same level in both dietary groups between 3 and 8 mo, although the fraction was greater in DR rats at 3 mo. In AL rats, the fraction decreased further between 8 and 20 mo, while it stabilized in DR rats. Our results suggested that dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats. Although one must also estimate the effects of dietary restriction on apoptotic cell death in pituitary cells, the present study provides evidence that dietary restriction modulates somatotropes cell turnover and preserves the cell population for GH secretion during aging.

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References

  1. Ceda, G.P., Valenti, G., Butturini, U., Hoffman, A. R.: Diminished pituitary responsiveness to growth hormone-releasing factor in aging male rats. Endocrinology, 118:2109–2114, 1986.

    Article  CAS  PubMed  Google Scholar 

  2. Millard, W.J., T.M. Romano, and J.W. Simpkins: Growth hormone and thyrotropin secretory profiles and provocative testing in aged rats. Neurobiol. Aging, 11: 229–235, 1990.

    Article  CAS  PubMed  Google Scholar 

  3. Sonntag, W.E., Hylka, V.W., and Meites, J.: Impaired ability of old male rats to secrete growth hormone in vivo but not in vitro in response to hpGRF (1–44). Endocrinology, 113: 2305–2307, 1983.

    CAS  PubMed  Google Scholar 

  4. Corpas, E., Harman, S.M., and Blackman, M.R.: Human growth hormone and human aging. Endocr Rev., 14: 20–39, 1993.

    Article  CAS  PubMed  Google Scholar 

  5. Shimokawa, I., Higami, Y., Okimoto, T., and Ikeda, T.: The growth hormone-releasing hormone-cyclic adenosine-3′,5′-monophosphate signal pathway in somatotropes is practically intact during aging. Neuroendocrinology, 60: 575–580, 1994.

    CAS  PubMed  Google Scholar 

  6. Shimokawa, I., Yu, B.P., Higami, Y., and Ikeda, T.: Morphometric analysis of somatotrophs: The effects of age and dietary restriction. Neurobiol. Aging, 17: 79–86, 1996.

    Article  CAS  PubMed  Google Scholar 

  7. Shimokawa, I., Higami, Y., Okimoto, T., Tomita, M., and Ikeda, T.: Effects of lifelong dietary restriction on somatotropes: Immunohistochemical and functional aspects. J. Gerontol.: Biol. Sci., 51A: B396–B402, 1996.

    CAS  Google Scholar 

  8. Masoro, E.J.: Food restriction in rodents: An evaluation of its role in the study of aging. J. Gerontol.: Biol. Sci., 43: B59–B64, 1988.

    CAS  Google Scholar 

  9. Weindruch, R. and Walford, R.L.: The retardation of aging and disease by dietary restriction, Springfield, Charles C Thomas Publisher, 1988.

    Google Scholar 

  10. Yu, B.P.: Modulation of aging processes by dietary restriction, Boca Raton, CRC Press, 1994.

    Google Scholar 

  11. Cameron, I.L.: Cell proliferation and renewal in aging mice. J. Gerontol., 27: 162–172, 1972.

    CAS  PubMed  Google Scholar 

  12. Warner, H.R., Fernandes, G. and Wang, E.: A unifying hypothesis to explain the retardation of aging and tumorigenesis by caloric restriction. J Gerontol.: Biol Sci, 50A: B107–B109, 1995.

    Google Scholar 

  13. Shimokawa, I., Yu, BP., Higami, Y., Okimoto, T., and Ikeda, T.: Age-related change and effect of dietary restriction in proliferation of GH cells of the anterior pituitary of male Fischer 344 rats. in Recent Advances in Aging Science, edited by Beregi, E, Gergely, I.A., and Rajczi, K. Bologna, Italy, Monduzzi Editore, 1993, pp. 289–292.

    Google Scholar 

  14. Nouet, J.C. and Kujas, M.: Variations of mitotic activity in the adenohypophysis of male rats during a 24-hour cycle. Cell Tissue Res., 164: 193–200, 1975.

    CAS  PubMed  Google Scholar 

  15. Carbajo-Perez, E., Carbajo, S., Orfao, A., Vicente-Villardon, J.L., and Vazquez, R.: Circadian variation in the distribution of cells throughout the different phases of the cell cycle in the anterior pituitary gland of adult male rats as analysed by flow cytometry. J. Endocrinol., 129: 329–333, 1991.

    CAS  PubMed  Google Scholar 

  16. De Bruine, A.P., Dinjens, W.N.M., Zijlema, J.H.L., Lenders, M.-H., Bosman, F.T.: Renewal of enterochromaffin cells in the rat caecum. Anat. Rec., 233: 75–82, 1992.

    Article  PubMed  Google Scholar 

  17. Keenan, K.P., Smith, P.F., Hertzog, P., Soper, K., Ballam, G.C., and Clark, R.L.:The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging. Toxicol. Pathol., 22: 300–315, 1994.

    Article  CAS  PubMed  Google Scholar 

  18. Carbajo-Perez, E., Motegi, M. and Watanabe, Y.G.: Cell proliferation in the anterior pituitary of mice during growth. Biomed. Res., 10: 275–281, 1989.

    Google Scholar 

  19. MacKenzie, W.F. and Boorman, G.A.: Pituitary gland, in Pathology of the Fischer Rat, edited by Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery, C.A. Jr., and MacKenzie, W.F., San Diego, Academic Press, 1990, pp. 485–500.

    Google Scholar 

  20. Frawley, L.S. and Boockfor, F.R: Mammosomatotropes: Presence and functions in normal and neoplastic pituitary tissue. Endocr. Rev., 12: 337–355, 1991.

    Article  CAS  PubMed  Google Scholar 

  21. Billestrup, N., Swanson, L.W., and Vale, W.: Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc. Natl. Acad. Sci. USA, 83: 6854–6857, 1986.

    CAS  PubMed  Google Scholar 

  22. Lin, S.-C., Lin, C.-R., Gukovsky, I., Lusis, A.J., Sawchenko, P.E., Rosenfeld, M.G.: Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature, 364: 208–213, 1993.

    Article  CAS  PubMed  Google Scholar 

  23. Morimoto, N., Kawakami, F., Makino, S., Chihara, K., Hasegawa, M., and Ibata, Y.: Age-related changes in growth hormone releasing factor and somatostatin in the rat hypothalamus. Neuroendocrinology, 47: 459–464, 1988.

    CAS  PubMed  Google Scholar 

  24. de Gennaro Colonna, V., Zoli, M., Cocchi, D., Maggi, A., Marrama, P., Agnati, L. F., and Mueller E.E.: Reduced growth hormone releasing factor (GHRH)-Iike immunoreactivity and GHRH gene expression in the hypothalamus of aged rats. Peptides, 10: 705–708, 1989.

    Article  CAS  Google Scholar 

  25. Sonntag, W.E., Xu, X., Ingram, R.L., D’Costa, A.: Moderate caloric restriction alters the subcellular distribution of somatostatin mRNA and increases growth hormone pulse amplitude in aged animals. Neuroendocrinology, 61:601–608, 1995.

    CAS  PubMed  Google Scholar 

  26. Sarkar, N.H., Fernandes, G., Telang, N.T., Kourides, I.A., and Good, R.A.: Low-calorie diet prevents the development of mammary tumors in C3H mice and reduces circulating prolactin level, murine mammary tumor virus expression, and proliferation of mammary alveolar cells. Proc. Natl. Acad. Sci. USA, 79: 7758–7762, 1982.

    CAS  PubMed  Google Scholar 

  27. Lok, E., Scott, F.W., Mongeau, R., Nera, E.A., Malcolm, S., and Clayson, D.B.: Calorie restriction and cellular proliferation in various tissues of the female Swiss Webster mouse. Cancer lett., 51: 67–73, 1990.

    Article  CAS  PubMed  Google Scholar 

  28. James, S.J. and Muskhelishvili, L.: Rates of apoptosis and proliferation vary with caloric intake and may influence incidence of spontaneous hepatoma in C57BL/6 × C3H F1 mice. Cancer Res., 54: 5508–10, 1994.

    CAS  PubMed  Google Scholar 

  29. Merry, B.J. and Holehan, A.M.: In vivo DNA synthesis in the dietary restricted long-lived rat. Exp. Gerontol., 20: 15–28, 1985.

    Article  CAS  PubMed  Google Scholar 

  30. Higami, Y., Shimokawa, I., Okimoto, T., and Ikeda, T.: Effect of aging and dietary restriction on hepatocyte proliferation, death and turnover in male F344 rats. Cell Tissue Res, in press.

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Correspondence to Isao Shimokawa MD.

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Shimokawa, I., Tomita, M., Higami, Y. et al. Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats. AGE 20, 169–174 (1997). https://doi.org/10.1007/s11357-997-0016-y

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  • DOI: https://doi.org/10.1007/s11357-997-0016-y

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