Rousseau N, Brazeau P, Lapierre H, Abribat T
Neuroendocrinology Laboratory, Louis-Charles Simard Research Centre, Montreal, Canada.
Growth Horm IGF Res. 1998 Oct;8(5):403-9. doi: 10.1016/s1096-6374(98)80311-0.
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.
生长激素（GH）和胰岛素样生长因子-I（IGF-I）在成年人中的生理作用，除了对组织生长的影响外，还在于维持机体的完整性。有人提出，成年后期这两种激素的可利用性降低，可能有助于引发正常人类衰老所特有的身体成分的主要改变和衰老变化。由于越来越多的证据表明GH与软骨中的软骨细胞存在直接相互作用，我们在本研究中确定了衰老对大鼠培养软骨细胞基础和GH刺激的IGF-I产生的影响。具体而言，我们研究了0、10和100 ng/ml生长激素对来自2、6、14和18月龄大鼠的单层培养肋软骨细胞在1、2、4和8天期间IGF-I水平的影响。IGF-I水平的测量是在经过验证的甲酸加热-丙酮提取程序后通过放射免疫测定法进行的。在6和14月龄大鼠软骨细胞中，基础IGF-I分泌高于2月龄对照大鼠。在18月龄大鼠软骨细胞中，基础IGF-I分泌低于任何其他年龄组。在2、6和14月龄大鼠软骨细胞中，GH诱导了剂量相关的IGF-I反应，在第8天具有高度显著性，而18月龄大鼠软骨细胞对GH处理不再有反应。我们的结果表明，培养的大鼠软骨细胞中IGF-I产生的减少可能与衰老过程中GH分泌减弱有关。因此，衰老过程中GH的可利用性似乎是组织反应性的一个决定性因素，并强调了GH替代可能具有对抗衰老衰老变化的治疗潜力这一假设。
