Simon L S, Slovik D M, Neer R M, Krane S M
Department of Medicine, Harvard Medical School, New England Deaconess Hospital, Boston, MA.
J Bone Miner Res. 1988 Apr;3(2):241-6. doi: 10.1002/jbmr.5650030218.
Parathyroid hormone (PTH) inhibits collagen synthesis in vitro, in organ or cell culture and cell-free translation systems. We have designed studies to measure the effects of PTH on collagen synthesis in vivo in humans, utilizing measurements of the serum levels of procollagen extension peptides during and after infusion of synthetic human PTH (hPTH) fragment (1-34). Radioimmunoassays for the carboxy-terminal peptide of type I procollagen (pColl-C) and the amino-terminal peptide of type III procollagen (pColl-III-N) were used to measure acute changes in serum during and after hPTH(1-34). In all six osteoporotic subjects and two normal individuals, serum levels of pColl-I-C were decreased by 16 hr of infusion and returned towards normal 14 hr after the infusion was discontinued; serum levels of pColl-III-N did not change significantly during the infusion, but were increased at 14 hr after the infusion was discontinued. The PTH-induced decrease in levels of pColl-I-C correlated with an increase in blood levels of ionized calcium. In all but two subjects the serum levels of 1,25-dihydroxy vitamin D [1,25(OH)2D] were also increased during the period when serum levels of pColl-I-C were decreased. These results are compatible with the conclusion that infusion of PTH acutely inhibits type I (bone) collagen synthesis, but not type III collagen synthesis. These effects could be direct or indirect, related in part to PTH-induced increased 1-alpha-hydroxylation of 25-(OH) vitamin D and the resultant increased serum levels of 1,25(OH)2D.
甲状旁腺激素(PTH)在体外、器官或细胞培养以及无细胞翻译系统中均可抑制胶原蛋白的合成。我们设计了多项研究,通过测量合成人PTH(hPTH)片段(1-34)输注期间及之后血清中前胶原延伸肽的水平,来测定PTH对人体体内胶原蛋白合成的影响。采用针对I型前胶原羧基末端肽(pColl-C)和III型前胶原氨基末端肽(pColl-III-N)的放射免疫测定法,来检测hPTH(1-34)输注期间及之后血清中的急性变化。在所有6名骨质疏松症患者和2名正常个体中,输注16小时后pColl-I-C的血清水平下降,在输注停止14小时后恢复至正常水平;pColl-III-N的血清水平在输注期间无显著变化,但在输注停止后14小时升高。PTH诱导的pColl-I-C水平下降与离子钙血水平升高相关。除两名受试者外,在pColl-I-C血清水平下降期间,所有受试者的1,25-二羟维生素D [1,25(OH)2D]血清水平也升高。这些结果与以下结论相符:输注PTH可急性抑制I型(骨)胶原蛋白的合成,但不抑制III型胶原蛋白的合成。这些作用可能是直接的,也可能是间接的,部分与PTH诱导的25-(OH)维生素D 1-α-羟化增加以及由此导致的1,25(OH)2D血清水平升高有关。