PARATHYROID-HORMONE ENHANCES THE TRANSCRIPT AND POLYPEPTIDE LEVELS OF INSULIN-LIKE GROWTH FACTOR-I IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
PARATHYROID-HORMONE ENHANCES THE TRANSCRIPT AND POLYPEPTIDE LEVELS OF INSULIN-LIKE GROWTH FACTOR-I IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
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DOI：
10.1210/endo-124-3-1247
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发表时间：
1989-03-01
期刊：
影响因子：
4.8
通讯作者：
CANALIS, E
中科院分区：
文献类型：
--
作者：
MCCARTHY, TL;CENTRELLA, M;CANALIS, E
PTH刺激骨吸收和形成，但其合成代谢作用的机制尚不清楚。PTH对骨形成的影响可以通过局部调节剂介导，通过改变其与受体的结合或通过调节其合成。通过北方印迹分析检测从胎鼠顶骨分离的PTH处理的成骨细胞富集培养物的细胞提取物中编码胰岛素样生长因子I（IGF-1）、转化生长因子-β和β 2-微球蛋白。PTH不影响转化生长因子-β。或β 2-微球蛋白转录水平。相比之下，PTH-（1-34）对IGF-I转录水平具有双相刺激作用; 0.1-10 nM PTH在6小时处理后使IGF-I转录增加100-200%，而100 nM PTH诱导100%增加。此外，0.01-10 nM的PTH在24 h时使培养基中的免疫反应性IGF-I（iIGF-I）增加40-200%。IGF-I转录物的最大增加发生在6小时，而iIGF-I在整个24小时的培养中积累。将这些结果与0.5-50 nM GH的作用进行比较，后者使IGF-I转录物增加30%，iIGF-I增加50- 100%。因此，PTH通过增加IGF-I转录物来增强局部IGF-I合成，这种作用可能部分介导PTH对骨的合成代谢作用。
PTH stimulates bone resorption and formation, but the mechanism of its anabolic effect is unknown. The effects of PTH on bone formation could be mediated by local regulators, either by altering their binding to receptors or by modulating their synthesis. Cell extracts from PTH-treated osteoblast-enriched cultures isolated from fetal rat parietal bones were examined by Northern blot analysis for changes in mRNAs encoding insulin-like growth factor I (IGF-I), transforming growth factor-.beta., and .beta.2-microglobulin. PTH did not influence transforming growth factor-.beta. or .beta.2-microglobulin transcript levels. In contrast, PTH-(1-34) had a biphasic stimulatory effect on IGF-I transcript levels; 0.1-10 nM PTH increased IGF-I transcripts by 100-200% after a 6-h treatment, while 100 nM PTH induced a 100% increase. In addition, PTH at 0.01-10 nM increased immunoreactive IGF-I (iIGF-I) in culture medium by 40-200% at 24 h. Maximal increases in IGF-I transcripts occurred at 6 h, while iIGF-I accumulated throughout 24 h of culture. These results are compared to the effects of 0.5-50 nM GH, which increased IGF-I transcripts by 30% and iIGF-I by 50-100%. Therefore, PTH enhanced local IGF-I synthesis by increasing IGF-I transcripts, and this effect may in part mediate the anabolic actions of PTH on bone.