Huan Jinxing, Olgaard Klaus, Nielsen Lars Bo, Lewin Ewa
Nephrological Department P, Rigshospitalet, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
J Am Soc Nephrol. 2006 Jul;17(7):1923-30. doi: 10.1681/ASN.2005101136. Epub 2006 May 17.
Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.
已证实，大的C末端甲状旁腺激素（PTH）片段的生物学效应与N末端PTH的生物学效应相反。C末端PTH片段与甲状旁腺分泌的N末端PTH共同分泌。我们研究的目的是检测C末端PTH 7-84是否调节PTH 1-84的分泌，并影响与甲状旁腺功能相关的基因、PTH、钙敏感受体（CaR）、1型PTH受体（PTHR1）和PTH相关肽（PTHrP）基因在大鼠甲状旁腺中的表达。PTH 7-84可使甲状旁腺完整的大鼠血浆Ca2+显著降低。尽管血浆Ca2+降低，但未发生PTH 1-84分泌的刺激。此外，PTH 7-84可显著抑制PTH 1-84对EGTA诱导的急性和严重低钙血症的分泌反应。在从低钙血症恢复过程中，与载体组相比，PTH 7-84治疗组的血浆Ca2+水平显著降低，同时血浆PTH 1-84水平被显著抑制。PTH 7-84不影响大鼠甲状旁腺中PTH、CaR、PTHR1和PTHrP基因的表达。PTH 7-84不影响PTH 1-84的外周代谢。PTH 7-84与大鼠生物活性PTH 1-84检测无交叉反应。在甲状旁腺完整的正常大鼠中，PTH 7-84抑制PTH 1-84对低钙血症的分泌反应，并使血浆Ca2+显著降低。PTH 7-84对PTH 1-84分泌和血浆Ca2+水平的这些影响与大鼠甲状旁腺中PTH, PTHR1, CaR和PTHrP基因表达的显著变化无关。据推测，PTH 7-84通过自分泌/旁分泌调节机制调节PTH分泌。
