Abstract
The present study was undertaken to elucidate the effect of the exogenous administration of rhGH on the time course of the cellular muscle growth in male and female BALB/c mice fed 20% dietary protein between weaning and 50 days of age. Also, the efficiency of utilization of protein and energy intake to muscle DNA content and protein per cell (protein to DNA ratio) storage were studied. 120 weaned mice (21 d) were assigned to four groups based on rhGH-treatment (rhGH-treated: 7.4 ng.g−1 BW and control: saline vehicle; via s.c. every two days) and gender. Feed intake was measured daily. At 25, 30, 35, 40, 45 and 50 days of age twenty mice were killed by cervical dislocation and the samples of gastrocnemius muscles were isolated, weighed and protein and DNA contents were measured. The rhGH administration caused a biphasic response altering the muscle cellular growth as a consequence of age-specific feed intake changes. The GH-induced fall of feed intake between 25 and 30 days of age caused decreases in muscle weight and myonuclei number (DNA), whereas muscle cell size was maintained. Later on, the self-controlled increase of feed intake led to the muscle weight recovery to control level, in spite of the irreversible DNA fall, as a consequence of the increase of cellular protein deposition and an enhancement of utilization of protein and energy intakes to deposit protein per cell. These results demonstrate that in spite of the initial (25–30 d of age) muscle DNA fall, rhGH-administration from weaning ensures the recovery of cellular muscle growth to control level through a compensatory muscle hypertrophy.
Resumen
Se estudia el efecto de la administración exógena de la hormona de crecimiento recombinante humana (rhGH) sobre el crecimiento celular del músculo esquelético, así como la eficacia de utilización de la ingesta en el depósito de DNA y proteína/DNA muscular en ratones BALB/c de ambos sexos entre el destete y 50 días de vida, alimentados con una dieta del 20% de proteína. Una vez destetados (21 días), los animales se distribuyen en 4 grupos según sexo (macho y hembra) y tratamiento: rhGH-tratados (74ng/g vía s.c) y controles (solución salina). A los 25, 30, 35, 40, 45 y 50 días de vida se sacrifican 20 ratones por dislocación cación cervical, se extrae el músculo gastrocnemio y se determinan el peso muscular y el contenido de proteína y DNA. La administración de rhGH da lugar a una respuesta bifásica alterando la forma del crecimiento celular en relación con los cambios en la ingesta. La caída inicial de la ingesta (entre 25 y 30 días) induce una drástica disminución en el peso muscular y el número de mionúcleos (DNA), mientras que el tamaño celular (proteína/DNA) se mantiene. Sin embargo, la posterior hiperfagia (35–50 días) facilita la recuperación del peso muscular a valor control, pese a la irreversibilidad de la pérdida del DNA. Esto se produce a consecuencia del incremento del tamaño celular, al cual contribuye el aumento en la eficacia de utilización de la energía y la proteína de la dieta en el depósito proteico muscular. Ello sugiere que, a pesar de la deplección inicial de sustratos, la administración de rhGH a ratones en el momento del destete asegura la recuperación del crecimiento celular del músculo gastrocnemio a través de un mecanismo de hipertrofia compensadora.
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References
Adams, G. R., Haddad, F. and Baldwin, K. M. (1999):J. Appl. Physiol.,87, 1705–1712.
Asakawa, K., Hizuka, N., Takano, K., Horikawa, R., Sukegawa, I., Demura, J. and Shizume, K. (1992):Growth Reg.,2, 40–44.
Azain, M. J., Hausman, B. D., Kasser, T. R. and Martin, R.J. (1995):Am. J. Physiol.,269, 137–144.
Booth, F. W. and Thomason, D.B. (1991):Physiol. Res.,71, 541–585.
Burton, K. (1956):Biochem. J.,62, 315–323.
Caperna, T.J., Komarek, D. R., Gavelek, D. and Steele, N. C. (1991):J. Anim. Sci.,69, 4019–4029.
Cheek, D. B. (1985):Early Hum. Dev.,12, 211–239.
Enesco, M. and Leblond, C. P. (1962):J. Embryol. Exp. Morph.,10, 530–562.
Gautsch, T. A., Kandl, S. M., Donovan, S. M. and Layman, D. K. (1999):J. Nutr.,129, 828–837.
Glore, S. R. and Layman, D. K. (1987):J. Nutr.,117, 1767–1774.
Goldspink, D. F. and Golberg, A. L. (1975):Am. J. Physiol.,228, 301–309.
Issad, T., Coupé, C., Pastor-Anglada, M., Ferré P. and Girard, J. (1988):Biochem. J.,251, 685–690.
Kidwell, J. F. and Howard, A. (1969):J. Nutr.,107, 61–69.
López-Oliva, M. E., Agis-Torres, A., Unzaga, M. T. and Muñoz-Martinez, E. (1995):Can. J. Anim. Sci.,75, 593–601.
López-Oliva, M. E., Agis-Torres, A., Unzaga, M. T. and Muñoz-Martínez, E. (2000):J. Physiol. Biochem.,56, 9–16.
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randeel, R. (1951):J. Biol. Chem.,193, 265–275.
McCall, G. E., Allen, D. L., Linderman, J. K., Grindeland, R. E., Roy, R. R., Mukku, V. R. and Edgerton, V. R. (1998):J. Appl. Physiol.,84, 1407–1412.
McCusker, R. H. and Campion, D. R. (1986):J. Endocrinol.,111, 279–285.
Milliken, G. A. and Johnson, D. E. (1984): “Analysis of messy data. Volume I: Designed Experiments”. Van Nostrand Reinhold, New York, pp. 29–45.
Moss, F. P. and Leblond, C. P. (1971):Anat. Rec.,170, 421–435.
Phelan, J. N. and Gonyea, W. J. (1997):Anat. Rec.,247, 179–188.
Rosenblatt, J. D. and Parry, D. J. (1993):Pflügers Arch.,423, 255–264.
Rosenblatt, J. D., Young, D. and Parry, D. J. (1994):Muscle Nerve.,17, 608–613.
Searle, T. W., Murray, J. D. and Baker, P. J. (1992):J. Endocrinol.,132, 285–291.
Sharma, A., Lee, Y. B., Murray, J. D. and, Oberbauer, A. M. (1996):Growth Dev. Aging,60, 31–41.
Solomon, M. B., Caperna, T. J., Mroz, R. J. and Steele, N. C. (1994):J. Anim. Sci.,72, 615–621.
Sommerland, H., Ullman, M., Jennische, E., Skottner, E. and Oldfors, A. (1989):Acta Neuropathol.,78, 264–269.
Sorensen, M. T., Oksbjerg, N., Agergaard, N. and Petersen, J.S. (1996):Comp. Biochem. Physiol.,113, 91–96.
Ullman, M. and Oldfors, A. (1989):Acta Physiol. Scand.,135, 531–536.
Vann, R. C., Althen, T. G., Smith, W. K., Veenhuizen, J. J. and Smith, S. B. (1998):J. Anim. Sci.,76, 1371–1379.
Wallace, T. D., and Silver, J. L. (1988): Econometrics, An Introduction. Addison-Wesley Publishing. Massachusetts, USA.
Zhao, X., Unterman, T. G. and Donovan, S. M. (1995):J. Nutr.,125, 1316–1327.
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López-Oliva, M.E., Agis-Torres, A. & Muñoz-Martínez, E. Growth hormone administration produces a biphasic cellular muscle growth in weaning mice. J. Physiol. Biochem. 57, 255–263 (2001). https://doi.org/10.1007/BF03179819
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DOI: https://doi.org/10.1007/BF03179819