GROWTH-HORMONE GENE-EXPRESSION AND SECRETION IN AGING RATS IS AGE-DEPENDENT AND NOT AGE-ASSOCIATED WEIGHT INCREASE RELATED

GH secretion declines with age in rats and humans and a reduction in G H gene expression has been demonstrated in aging rats. GH secretion al so diminishes in obesity; thus, the aim of this study was to determine whether GH decrease in aging rats is clue to body weight gain or to a ging. 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 differe nt 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, th e effects due to aging itself could be determined. Body weight (g, mea n +/-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-La, IGF-Lb mRNA t ranscripts and IGFBP-3 mRNA accumulation in the liver showed no signif icant differences between the two groups. On the contrary, when the 27 -month-old rats were compared with the 11-month-old animals, lower lev els of pituitary GH mRNA and serum and pituitary IR-GH were found. Pit uitary GH mRNA decreased 37.5 +/- 7.7% P < 0.001, pituitary IR-GH cont ent diminished (5.2 +/- 3.4 vs. 55 +/- 10.7 ng/mg of protein, P < 0.00 1) and serum IR-GH decreased(3.5 +/- 1.8 vs. 12.5 +/- 4.2 ng/ml, P < 0 .01). Liver IGF-La and IGF-Lb mRNA transcripts accumulation and serum IGF-I were significantly diminished. IGF-Lb mRNA accumulation decrease d 35.8 +/- 1.2% P < 0.05 and IGF-La 36 +/- 5.6% P < 0.05; serum IR-IGF -I levels diminished (759 +/- 152 vs. 1327 +/- 67 ng/ml, P < 0.05). Li ver IGFBP-3 mRNA accumulation decreased 79 +/- 4.2% P < 0.001. These r esults 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 IG FBP-3, is due to aging and not to the increase in body weight that tak es place with aging.