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Growth Hormone Gene Expression and Secretion in Aging Rats Is Age Dependent and Not Age-Associated Weight Increase Related¹

Servicio de Endocrinología, CIC, Instituto de Salud Carlos III (B.V., J.E., F.S-F.), C/Sinesio Delgado, 10-12, Madrid 28029, Spain; and Servicio de Endocrinología, Hospital Ramón y Cajal (L.C., J.L.-F.), Ctra. Colmenar Km 9.0, Madrid 28034, Spain

Address all correspondence and requests for reprints to: F. Sanchez-Franco, Centro de Investigacions Clinicas de Salud Instituto Carlos III, Servicio de Endocrinologia, C/Sinesio Delgado, 10, Madrid 28029, Spain.

GH secretion declines with age in rats and humans and a reduction in GH gene expression has been demonstrated in aging rats. GH secretion also diminishes in obesity; thus, the aim of this study was to determine whether GH decrease in aging rats is due to body weight gain or to aging. Three groups of male Wistar rats of different ages were studied (young, 3 months; middle-aged, 11 months; old, 27 months). The middle-aged group was established on a statistical analysis and corresponded to the youngest age at which body weight was not significantly different from the old (27 month) group. Thus, by using this group as control for comparison with animals with the same weight and an older age, the effects due to aging itself could be determined. Body weight (g, mean ±SD) 3 months: 361 ± 5.6; 11 months: 713 ± 39; 27 months: 635 ± 38. In comparison with 3-month-old rats, the 11-month-old animals showed no difference in pituitary GH messenger RNA (mRNA) accumulation and pituitary and serum IR-GH levels. Similarly IGF-I.a, IGF-I.b mRNA transcripts and IGFBP-3 mRNA accumulation in the liver showed no significant differences between the two groups. On the contrary, when the 27-month-old rats were compared with the 11-month-old animals, lower levels of pituitary GH mRNA and serum and pituitary IR-GH were found. Pituitary GH mRNA decreased 37.5 ± 7.7% P < 0.001, pituitary IR-GH content diminished (5.2 ± 3.4 vs. 55 ± 10.7 ng/mg of protein, P < 0.001) and serum IR-GH decreased (3.5 ± 1.8 vs. 12.5 ± 4.2 ng/ml, P < 0.01). Liver IGF-I.a and IGF-I.b mRNA transcripts accumulation and serum IGF-I were significantly diminished. IGF-I.b mRNA accumulation decreased 35.8 ± 1.2% P < 0.05 and IGF-I.a 36 ± 5.6% P < 0.05; serum IR-IGF-I levels diminished (759 ± 152 vs. 1327 ± 67 ng/ml, P < 0.05). Liver IGFBP-3 mRNA accumulation decreased 79 ± 4.2% P < 0.001.

These results indicate that the decrease in GH gene expression and secretion, as well as the expression of genes induced by GH such as IGF-I and IGFBP-3, is due to aging and not to the increase in body weight that takes place with aging.

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