Research for the mechanisms of anabolic action of parathyroid hormone (PTH) and interaction between PTH and estrogen

众所周知，甲状旁腺激素(PTH)在骨骼中既有分解代谢作用，又有合成代谢作用，但其合成代谢作用机制尚不清楚。本研究表明，不仅胰岛素样生长因子(IGF)-I和IGF结合蛋白-5(IGFBP-5)参与了甲状旁腺素在骨中的合成代谢作用。虽然人们普遍认为PTH分子的生物活性主要存在于该分子的氨基末端，但也有几条证据表明，在羧基末端片段中也存在一些生物活性。本研究证实甲状旁腺素分子的羧基末端对成骨细胞I型前胶原和IGFBP-5的表达具有生物活性，这可能参与体内甲状旁腺素在骨中的合成代谢作用。此外，根据原发性甲状旁腺功能亢进症患者甲状旁腺切除术后骨量变化的临床研究表明，…进一步指出，内源性甲状旁腺素浓度的迅速降低在甲状旁腺素在骨中的合成代谢作用中起着至关重要的作用。另一方面，一些证据表明，雌激素在体内和体外都能抑制甲状旁腺激素诱导的骨吸收，但其确切机制尚不清楚。我们先前的研究表明，雌激素抑制甲状旁腺素诱导的未分离骨细胞中破骨细胞的形成，但目前仍不清楚甲状旁腺素和雌激素之间的这种相互作用是由骨中的哪种细胞负责的。本研究证明PTH受体和雌激素受体均存在于造血母细胞，即破骨细胞前体细胞中。雌激素通过直接作用于造血母细胞抑制甲状旁腺激素诱导的破骨细胞形成，并通过阻断cAMP依赖的蛋白激酶介导雌激素抑制甲状旁腺激素诱导的破骨细胞形成。本研究表明，在没有雌激素的情况下，PTH诱导的破骨细胞生成增强，部分参与了与绝经后骨质疏松相关的破骨细胞数量的增加。较少

It is well known that parathyroid hormone (PTH) possesses catabolic as well as anabolic action in bone, but the mechanisms of its anabolic action remained unknown. The present study demonstrated that not only insulin-like growth factor (IGF)-I but also IGF-binding protein-5 (IGFBP-5) were involved in the anabolic action of PTH in bone. Although it has been generally accepted that the biological activity of the PTH molecule mainly exists in the amino-terminal region of this molecule, there have also been several lines of evidence that some biological activities exist in carboxyl-terminal fragment. The present study demonstrated that carboxyl-terminal portion of the PTH molecule exercised biological activities in mRNA expression of type-I procollagen as well as IGFBP-5 in osteoblasts and that these would be involved in the anabolic action of PTH in bone in vivo. Moreover, clinical studies obtained from changes in bone mass after parathyroidectomy in primary hyperparathyroidism demonstrat … More ed that rapid reduction in endogenous PTH concentration played a crucial role in the anabolic action of PTH in bone. On the other hand, several lines of evidence indicate that estrogen inhibits PTH-induced bone resorption in viva and invitro, but its precise mechanisms remained unclear. Our previous study demonstated estrogen inhibited PTH-induced osteoclast formation in unfractionated bone cells, but it remained still unclear what kind of cells in bone were responsible for this interaction between PTH and estrogen. The present study demonstrated that PTH receptors and estrogen receptors both existed in hemopoietic blast cells, that is, osteoclast precursor cells. Estrogen inhibited PTH- induced osteoclast formation by directly acting on hemopoietic blast cells and the inhibitory effects of estrogen on PTH-induced osteoclast formation were mediated through blocking cAMP-dependent protein kinase. The present study indicated that the enhanced PTH-induced osteoclastgenesis in the absence of estrogen was partly involved in the increase in osteoclast number associated with postmenopausal osteoporosis. Less