Gómez José Manuel
Endocrinology Service, Ciudad Sanitaria de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Curr Pharm Biotechnol. 2006 Apr;7(2):125-32. doi: 10.2174/138920106776597621.
Several factors are known to be involved in the regulation of vitamin D and sunlight and diet are the two sources in humans, but the relative importance of each of them is not well defined. Vitamin D, parathyroid hormone and serum insulin-like growth factor-I (IGF-I) were found to be independent predictors of total bone density. Thus, the growth hormone (GH)/IGF-I is thought to play an important role in the regulation of bone mineral density and the skeleton is second only to the liver as a source of circulating levels of IGF-I. The mechanisms by which IGF-I may influence bone metabolism is not fully understood but they are a predictor of bone mass density and are positively associated with vitamin D concentrations. There is a physiological decline of the GH/IGF axis with ageing. The high affinity IGF-binding proteins (IGFBP-I to 6) have also been involved in IGF-I regulation, and it is important to include the IGF-independent properties, particularly those of IGFBP3 that may be involved in the osteoblastic differentiation observed in human bone marrow stromal cell cultures. These hormones have been shown to up regulate each other. 1,25-(OH) D(3) has been shown to promote the action of IGF-I by increasing IGF-I receptors and IGF-I can also elevate 1,25-(OH) D(3) concentrations by stimulating the hydroxylation of 25-(OH) D(3) in the active 1,25-(OH) D(3) hormone. Both GH and IGF-I significantly increased renal 1alpha-hydroxylase expression and serum 1, 25-(OH) D(3) concentrations. In prostate cells, 1,25-(OH) D(3) is growth inhibitory for many established cell lines and the role of IGFBPs, especially IGFBP-3, can be growth inhibitory or stimulatory and IGFBP-3 expression increases in response to 1,25-(OH) D(3), or its analogs, in established prostate cancer cell lines. Body fat is inversely associated with 25-(OH) D(3) in relation to with anthropometric measures, indicating a specific role of adipose tissue. IGF-I may be involved in both normal and abnormal fetal growth and stimulation of IGF-I synthesis during normal pregnancy may be associated with an increase in GH production by the placenta. Thus, maternal and umbilical cord serum IGF-I and 1,25-(OH) D(3) concentrations are lower in preeclampsia and umbilical cord serum IGF-I, IGFBP-1 and IGFBP-3 concentrations are associated with low newborn birth weights.
已知有几个因素参与维生素D的调节，阳光和饮食是人类维生素D的两个来源，但它们各自的相对重要性尚未明确界定。维生素D、甲状旁腺激素和血清胰岛素样生长因子-I（IGF-I）被发现是总骨密度的独立预测指标。因此，生长激素（GH）/IGF-I被认为在骨矿物质密度的调节中起重要作用，而骨骼是循环中IGF-I水平的第二大来源，仅次于肝脏。IGF-I影响骨代谢的机制尚未完全了解，但它是骨密度的预测指标，且与维生素D浓度呈正相关。随着年龄增长，GH/IGF轴会出现生理性下降。高亲和力的IGF结合蛋白（IGFBP-1至6）也参与IGF-I的调节，纳入IGF非依赖性特性很重要，尤其是IGFBP3的特性，其可能参与人骨髓基质细胞培养中观察到的成骨细胞分化。这些激素已被证明相互上调。1,25-(OH)D(3)已被证明可通过增加IGF-I受体来促进IGF-I的作用，而IGF-I也可通过刺激25-(OH)D(3)羟化生成活性1,25-(OH)D(3)激素来提高1,25-(OH)D(3)浓度。GH和IGF-I均显著增加肾脏1α-羟化酶表达和血清1,25-(OH)D(3)浓度。在前列腺细胞中，1,25-(OH)D(3)对许多已建立的细胞系具有生长抑制作用，IGFBP的作用，尤其是IGFBP-3的作用，可能具有生长抑制或刺激作用，在已建立的前列腺癌细胞系中，IGFBP-3表达会因1,25-(OH)D(3)或其类似物而增加。与人体测量指标相关，体脂与25-(OH)D(3)呈负相关，表明脂肪组织具有特定作用。IGF-I可能参与正常和异常的胎儿生长，正常妊娠期间IGF-I合成的刺激可能与胎盘GH分泌增加有关。因此，先兆子痫患者的母血和脐血血清IGF-I及1,25-(OH)D(3)浓度较低，脐血血清IGF-I、IGFBP-1和IGFBP-3浓度与新生儿低体重有关。
