An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats
An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats
复制标题
DOI：
10.1359/jbmr.1997.12.3.384
复制
发表时间：
1997-03-01
影响因子：
6.2
通讯作者：
Civitelli, R
中科院分区：
文献类型：
--
作者：
ArmamentoVillareal, R;Ziambaras, K;Civitelli, R
在动物和人类骨质疏松模型中，间歇性给予甲状旁腺激素（PTH）肽增加骨密度。体外研究表明，缺乏前两个氨基酸的甲状旁腺激素类似物可以刺激某些细胞系统中的细胞增殖，而具有完整N端的片段可以抗生丝。通过监测6个月大的卵巢切除（OVX）大鼠的骨密度和股骨的生物力学特性，我们测试了截断的PTH（3-38）片段是否比PTH（1-38）片段更好（“合成代谢类似物”）。两种PTH片段都是每周5天皮下注射（8 μ g/100 g体重），持续4周，从手术后1周开始，在整个研究中，未经治疗的OVX大鼠失去了12.1 +/- 4.4%的初始骨密度，PTH（1-38）逆转了初始骨质流失。相反，给予PTH（3-38）导致骨质流失13.2 +/- 5.8%，而持续雌激素输注（10 μ g/kg/天）可以防止骨质流失但不能逆转骨质流失，假手术动物在载具组和PTH（3-38）处理组也出现了明显的骨质流失（分别为-4.5 +/- 6.7%和-7.6 +/- 2.8%）。而在PTH治疗的大鼠中，骨密度显著增加（+4.4 +/- 5.6%）（1-38）。与假手术动物相比，用载体或PTH治疗的OVX动物外植的股骨的骨质量因子（应变能损失指数）和冲击强度（抗骨折性）分别降低了25%和44%（3-38）。相反，用PTH治疗的OVX动物和对照动物之间没有观察到差异（1-38），表明保留了承受机械应力的能力。PTH（1-38）抵消雌激素依赖的矿物质密度和骨生物力学性能的损失，并增加雌激素充满动物的骨密度。完整的N端序列是PTH合成代谢作用所必需的。
Intermittent administration of parathyroid hormone (PTH) peptides increases bone density in animal and human models of osteoporosis, In vitro studies have demonstrated that PTH analogs lacking the first two amino acids can stimulate cell proliferation in certain cell systems, whereas fragments with an intact N terminus can be antimitogenic, We have tested whether the truncated PTH(3-38) fragment may be a better ((anabolic analog'' than PTH(1-38) by monitoring bone density and biomechanical properties of the femur in 6-month-old ovariectomized (OVX) rats, Either PTH fragment was administered subcutaneously (8 mu g/100 g of body weight) 5 days/week, for 4 weeks, starting 1 week after surgery, During the entire study, untreated OVX rats lost 12.1 +/- 4.4% of their initial bone density, PTH(1-38) reversed the initial bone loss, leading to complete restoration of presurgery values after 4 weeks of treatment, Conversely, administration of PTH(3-38) resulted in 13,2 +/- 5.8% bone loss, while continuous estrogen infusion (10 mu g/kg/day) prevented bone loss hut did not reverse it, Sham-operated animals also experienced significant bone loss in the vehicle and PTH(3-38)-treated groups (-4.5 +/- 6.7% and -7.6 +/- 2.8%, respectively), whereas a significant gain in bone density (+4.4 +/- 5.6%) was observed in the rats treated with PTH(1-38). A bone quality factor (index of strain energy loss) and the impact strength (resistance to fracture) were 25% and 44% lower in femurs explanted from OVX animals treated with either vehicle or PTH(3-38), compared with sham-operated animals, On the contrary, no difference was observed between OVX and control animals after treatment with PTH(1-38), indicating a preservation of the capacity to withstand mechanical stress, Thus, PTH(1-38) counteracts estrogen-dependent loss of mineral density and bone biomechanical properties and increases bone density in estrogen-replete animals, An intact N terminus sequence is necessary for this anabolic action of PTH.