Effect of aging on growth hormone-induced insulin-like growth factor-I secretion from cultured rat chondrocytes

The physiological roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in adult other than their effects on tissue growth is to maintain the integrity of the organism. It has been proposed that reduced availability of both hormones in late adulthood may contribute to the initiation of the major alterations and senescent changes in body composition that characterize normal human aging. Since accumulated evidence points to a direct interplay of GH with chondrocytes in cartilage, we determined in the present study the effect of aging on both basal and GH-stimulated IGF-I production from rat cultured chondrocytes. Namely, we investigated the effect of 0, 10 and 100 ng/ml of growth hormone on IGF-I levels during 1, 2, 4 and 8 days in monolayer cultured costal chondrocytes from 2-, 6-, 14- and 18-month-old rats. Measurement of IGF-I levels was done by a radioimmunoassay following a validated formic acid-heating-acetone extraction procedure. In 6- and 14-month-old rat chondrocytes, basal IGF-I secretion was higher than that of the 2-month-old control rats. In 18-month-old rat chondrocytes, basal IGF-I secretion was lower than in any other age group. Whereas in 2-, 6- and 14-month-old rat chondrocytes, GH induced a dose-related IGF-I response which was highly significant on day 8, the 18-month-old rat chondrocytes no longer responded to GH treatments. Our results suggest that the decrease in IGF-I production from cultured rat chondrocytes could be related to the blunted GH secretion in the course of aging. Therefore, GH availability in the course of aging appears to be a determinant factor in tissue responsiveness and underscores the hypothesis that GH replacement could present a therapeutic potential against the aging senescent changes.