Developmental change in calcium homeostasis during perinatal period

甲状旁腺激素和1,25-二羟基维生素D是提高血清钙水平的主要激素，而将血清钙控制在8.5-10 mg/dl左右主要是通过甲状旁腺钙敏感受体来控制人体甲状旁腺激素的分泌。然而，在胎儿时期，胎儿从母亲那里接受钙和磷，因此甲状旁腺激素和1,25-二羟基维生素D在维持胎儿高钙血症中的作用可能很小。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激素相关肽的作用，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中的作用。为此，我们还对新生儿时期发现的伴有高钙血症和家族性甲状旁腺功能低下的Jansen干骺端软骨发育不良进行了分析。脐带血中甲状旁腺激素相关肽浓度高，这可能导致胎儿和新生儿早期尿排泄减少。我们发现甲状旁腺钙敏感受体的组成性激活是新生儿期发现的严重家族性甲状旁腺功能低下的一个原因，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。Jansen干骺端软骨发育不良伴高钙血症，可导致PTH/PTHrP受体的组成性激活，分析表明胎儿时期PTH/PTHrP受体的表达可能较低。因此，我们研究了胎儿时期PTH/PTHrP受体mRNA的水平。我们也发现胎盘钙敏感受体和甲状旁腺激素相关蛋白在细胞滋养层原代培养细胞中均有表达，但其意义尚待进一步研究阐明。

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.