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Developmental change in calcium homeostasis during perinatal period

围产期钙稳态的发育变化

基本信息

批准号：
08670855
负责人：
YASUDA Toshiyuki
金额：
$ 1.6万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The parathyroid hormone and 1,25-dihydroxyvitamin D are principle hormones to raise serum calcium levels, and the control of serum calcium around 8.5-10 mg/dl is mainly achieved by the parathryoid calcium-sensing receptor to control parathryoid hormone secretion in man. However, during fetal life, the fetus receives calcium and phosphorus from mother, and consequently the role of parathyroid hormone and 1,25-dihydroxyvitamin D to maintain fetal hypercalcemia may be minor. We do not know the reason why the fetus maintain hypercalcemia. The aim of present study is to elucidate the role of parathyroid hormone-related peptide and the role of parathyroid calcium-sensing receptor and placenta calcium-sensing receptor during fetal and neonatal adaptation. For this porpose, analysis of Jansen metaphyseal chondrodysplasia with hypercalcemia and familial hypoparathyroidism identified during neonatal period was also performed. Parathyroid hormonerelated peptide concentration in cord blood was high which may contribute to a reduction in urine Caexcretion in fetal and early neonatal life. We revealed that a constitutive activation of parathyroid calcium-sensing receptor is a cause of severe familial hypoparathyroidism identified during neonatal period, which may indicate the role of parathyroid calcium-sensing receptor to maintain serum calcium level during perinatal period. Analysis of Jansen metaphyseal chondrodysplasia with hypercalcemia, which cause is constitutive activation of the PTH/PTHrP receptor, suggests that the expression of PTH/PTHrP receptor during fetal life may be low. Therefore, we have examined the level of the PTH/PTHrP receptor mRNA during fetal life. We have also identified that both placental calcium-sensing receptor and parathyroiod hormone-related protein are expressed in cytotrophoblast primary culture cell, however further study is required to elucidate their significance.

甲状旁腺素和1，25-二羟维生素D是提高血清钙水平的主要激素，将血清钙控制在8.5-10 mg/dl左右主要是通过类甲状腺素钙敏感受体来控制人的类甲状腺素分泌。然而，在胎儿期，胎儿从母亲那里接受钙和磷，因此甲状旁腺素和1，25-二羟维生素D的作用，25-二羟维生素D维持胎儿高钙血症可能是轻微的。我们不知道胎儿维持高钙血症的原因。本研究的目的是阐明甲状旁腺相关肽的作用，甲状旁腺钙敏感受体和胎盘钙敏感受体在胎儿和新生儿适应过程中的作用。为此目的，还分析了在新生儿期发现的Jansen干骺端软骨发育不良伴高钙血症和家族性甲状旁腺功能低下的病例。脐血甲状旁腺素相关肽浓度高，可能与胎儿及新生儿早期尿钙排泄减少有关。我们发现，甲状旁腺钙敏感受体的组成性激活是在新生儿期发现的严重家族性甲状旁腺功能减退症的原因，这可能表明甲状旁腺钙敏感受体在围产期维持血清钙水平的作用。分析Jansen干骺端软骨发育不良伴高钙血症，其原因是PTH/PTHrP受体的组成性激活，表明胎儿期PTH/PTHrP受体的表达可能较低。因此，我们研究了PTH/PTHrP受体mRNA的水平在胎儿的生活。我们还发现胎盘钙敏感受体和甲状旁腺素相关蛋白在细胞滋养层原代培养细胞中均有表达，但其意义尚需进一步研究。