Xu X, Sonntag W E
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.
J Gerontol A Biol Sci Med Sci. 1996 Mar;51(2):B167-74. doi: 10.1093/gerona/51a.2.b167.
A decline in plasma concentration of insulin-like growth factor-1 (IGF-1) has been hypothesized to contribute to a decrease in tissue protein synthesis and function in aging animals and man. In this study, the effects of aging and long-term caloric restriction on growth hormone receptor signal transduction were assessed in hepatic tissue to determine whether alterations in tissue responsiveness to growth hormone contribute to the decline in IGF-1 gene expression. Liver slices from female C57/BL mice (10, 17, and 31 months) were prepared in media and stimulated with growth hormone (2 nM). An increase in growth hormone receptor binding was observed in 31-month ad libitum-fed animals (p < .01) compared to 10- or 17-month-old animals), and this effect was partially attenuated by moderate caloric restriction. However, growth hormone (2 nM)-induced IGF-1 gene expression was significantly lower in old ad libitum-fed animals (p < .05 compared to 10-month-old ad libitum and 31-month-old caloric-restricted animals). Further analysis revealed that growth hormone receptor and JAK2 kinase phosphorylation as well as mitogen-activated protein (MAP) kinase activity were significantly lower in old animals compared to the adult or middle-age groups (p < .05). Old caloric-restricted animals demonstrated a significant increase in growth hormone receptor and JAK2 kinase phosphorylation and MAP kinase activity in response to growth hormone. The results demonstrate that growth hormone increases growth hormone receptor and JAK2 kinase phosphorylation as well as MAP kinase activity in liver. These responses decrease with age and are attenuated by moderate, long-term caloric restriction.
胰岛素样生长因子-1（IGF-1）血浆浓度的下降被认为是导致衰老动物和人类组织蛋白质合成及功能下降的原因。在本研究中，我们评估了衰老和长期热量限制对肝脏组织中生长激素受体信号转导的影响，以确定组织对生长激素反应性的改变是否导致IGF-1基因表达的下降。将雌性C57/BL小鼠（10、17和31月龄）的肝脏切片置于培养基中，并用生长激素（2 nM）刺激。与10或17月龄的动物相比，31月龄自由摄食的动物中观察到生长激素受体结合增加（p <.01），适度热量限制可部分减弱这种效应。然而，自由摄食的老年动物中生长激素（2 nM）诱导的IGF-1基因表达显著降低（与10月龄自由摄食和31月龄热量限制的动物相比，p <.05）。进一步分析表明，与成年或中年组相比，老年动物中生长激素受体和JAK2激酶的磷酸化以及丝裂原活化蛋白（MAP）激酶活性显著降低（p <.05）。热量限制的老年动物对生长激素的反应表现为生长激素受体和JAK2激酶磷酸化以及MAP激酶活性显著增加。结果表明，生长激素可增加肝脏中生长激素受体和JAK2激酶的磷酸化以及MAP激酶活性。这些反应随年龄增长而降低，并因适度的长期热量限制而减弱。
