Parathyroid Hormone Contributes to Regulating Milk Calcium Content and Modulates Neonatal Bone Formation Cooperatively with Calcium

Parathyroid Hormone Contributes to Regulating Milk Calcium Content and Modulates Neonatal Bone Formation Cooperatively with Calcium
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甲状旁腺激素有助于调节乳钙含量,并与钙协同调节新生儿骨形成

DOI:
10.1210/en.2008-0654
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发表时间:
2009-02-01
期刊:
影响因子:
4.8
通讯作者:
Miao, Dengshun
Miao, Dengshun
中科院分区:
医学2区
文献类型:
--
作者:
Cao, Guofan;Gu, Zhen;Miao, Dengshun

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为了确定PTH和钙(Ca)是否在新生儿骨形成过程中相互作用,雌性哺乳期小鼠分别饲喂PTH基因杂合(PTH+/-)或纯合(PTH-/-)靶向缺失PTH基因的正常(1% Ca, 0.6%磷酸盐)或高钙饮食(2% Ca和0.4%磷酸盐)。研究了饲粮对乳钙含量和钙调节激素的影响,并评估了乳钙含量对3周龄幼犬骨转换的影响。在正常饮食条件下,乳汁中钙和1,25-二羟基维生素D-3水平较低,但乳汁中甲状旁腺激素-/-组的甲状旁腺激素相关蛋白水平高于甲状旁腺激素+/-组。在高钙饲粮中,乳汁中的钙含量较高,但乳汁中的1,25-二羟基维生素D3和甲状旁腺素+/-和甲状旁腺素-/-的蛋白水平较低。与正常饲粮PTH+/-饲粮相比,PTH+/-饲粮的幼崽骨密度、骨小梁体积相对于组织体积和成骨细胞数量均降低(32.5 +/- 1.2 vs 39.6 +/- 1.5 mg/cm, P < 0.05);23.3 +/- 1.6 vs. 29.2 +/- 2.8%, P < 0.01;和94.2 + / - 8.2和123.5 + / - 3.5毫米(2),P < 0.01)和甲状旁腺素- / -(20.4 + / - 0.9和27.0 + / - 1.2毫克/毫米(2),P < 0.05;16.8 +/- 1.9 vs. 19.3 +/- 2.1%, P < 0.05;和48.6 +/- 7.9 vs. 90.5 +/- 8.6/mm(2), P < 0.01),但PTH-/-幼犬与PTH+/-幼犬相比,PTH-/-幼犬较低。相比之下,高钙饲粮中PTH+/-和PTH-/-喂养的幼崽,骨密度、骨体积/组织体积和成骨细胞数量显著高于PTH+/- (50.5 +/- 1.7 vs. 58.7 +/- 2.0 mg/mm) (2), P < 0.05;37.9 +/- 5.2 vs. 46.1 +/- 5.1, P < 0.05;和120.5 + / - 9.2和159.3 + / - 14.7毫米(2),P < 0.01,分别)和甲状旁腺素+ / -(33.0 + / - 1.2和47.5 + / - 2.2毫克/毫米(2),P < 0.001;23.8 +/- 3.1 vs. 35.9 +/- 2.0, P < 0.05;和78.7 +/- 10.1比99.8 +/- 13.6/mm(2), P < 0.05),且以高钙饲粮PTH-/-母鼠喂养的PTH+/-幼崽最高。上述结果表明,甲状旁腺激素可以调节乳汁中钙的含量,甲状旁腺激素和钙在新生儿成骨形成过程中各自发挥协同作用。(内分泌学150:561-569,2009)
To determine whether PTH and calcium (Ca) interact in neonatal bone formation, female lactating mice either heterozygous (PTH+/-) or homozygous (PTH-/-) for targeted deletion of the pth gene were fed either a normal (1% Ca, 0.6% phosphate) or high-Ca diet (2% Ca and 0.4% phosphate). Dietary effects on milk Ca content and Ca-regulating hormones were determined in dams, and the effects of milk content were assessed on bone turnover in 3-wk-old pups. On the normal diet, milk Ca and 1,25-dihydroxyvitamin D-3 levels were lower, but milk PTH-related protein levels were higher in the PTH-/- dams compared with the PTH+/- dams. On the high-Ca diet, milk Ca levels were higher, but milk 1,25-dihydroxyvitamin D3 and PTH-related protein levels were lower in both PTH+/- and PTH-/- dams. In pups fed by PTH-/- dams compared with pups fed by PTH+/- dams on normal diets, bone mineral density, trabecular bone volume relative to tissue volume, and the number of osteoblasts were reduced in both PTH+/- (32.5 +/- 1.2 vs. 39.6 +/- 1.5 mg/cm(2), P < 0.05; 23.3 +/- 1.6 vs. 29.2 +/- 2.8%, P < 0.01; and 94.2 +/- 8.2 vs. 123.5 +/- 3.5/mm(2), P < 0.01, respectively) and PTH-/- (20.4 +/- 0.9 vs. 27.0 +/- 1.2 mg/mm(2), P < 0.05; 16.8 +/- 1.9 vs. 19.3 +/- 2.1%, P < 0.05; and 48.6 +/- 7.9 vs. 90.5 +/- 8.6/mm(2), P < 0.01, respectively) pups but were lower in the PTH-/- pups compared with the PTH+/- pups. In contrast, in pups fed by either PTH+/- or PTH-/- dams on the high-Ca diet, bone mineral density, bone volume/tissue volume, and osteoblast numbers were significantly higher, in both PTH+/- (50.5 +/- 1.7 vs. 58.7 +/- 2.0 mg/mm(2), P < 0.05; 37.9 +/- 5.2 vs. 46.1 +/- 5.1, P < 0.05; and 120.5 +/- 9.2 vs. 159.3 +/- 14.7/mm(2), P < 0.01, respectively) and PTH+/- (33.0 +/- 1.2 vs. 47.5 +/- 2.2 mg/mm(2), P < 0.001; 23.8 +/- 3.1 vs. 35.9 +/- 2.0, P < 0.05; and 78.7 +/- 10.1 vs. 99.8 +/- 13.6/mm(2), P < 0.05, respectively), and were highest in the PTH+/- pups fed by the PTH-/- dams on the high-Ca diet. These results indicate that PTH can modulate Ca content of milk, and that PTH and Ca can each exert cooperative roles on osteoblastic bone formation in the neonate. (Endocrinology 150: 561-569, 2009)