PARATHYROID HORMONE-RELATED PEPTIDE GENE IS EXPRESSED IN THE MAMMALIAN CENTRAL NERVOUS-SYSTEM
PARATHYROID HORMONE-RELATED PEPTIDE GENE IS EXPRESSED IN THE MAMMALIAN CENTRAL NERVOUS-SYSTEM
复制标题
DOI：
10.1073/pnas.87.1.108
复制
发表时间：
1990-01-01
影响因子：
11.1
通讯作者：
ROBBINS, RJ
中科院分区：
文献类型：
--
作者：
WEIR, EC;BRINES, ML;ROBBINS, RJ
甲状旁腺素相关肽（PTHRP）已被确定在人类肿瘤与恶性肿瘤的体液性高钙血症综合征。虽然甲状旁腺激素（PTH）基因的表达似乎是有限的甲状旁腺，PTHRP mRNA已被确定在各种正常组织。为了研究PTHRP在中枢神经系统中的表观表达，我们通过在PTH敏感性测定中测量腺苷酸环化酶刺激活性（阿克萨）来检测全大鼠脑提取物的PTHRP生物活性。提取物始终含有阿克萨，并且该活性完全被PTHRP抗血清抑制，但不受PTH抗血清的影响。阿克萨被发现在一些解剖的大鼠脑的亚区，是最大的皮质和端脑。RNA酶保护分析显示PTHRP转录本从整个大鼠脑和相同的解剖亚区制备的总RNA。通过原位杂交组织化学，我们发现PTHRP基因的表达水平最高发生在大脑皮层，海马和小脑皮质的神经元。这些研究表明，PTHRP mRNA和生物活性都存在于大鼠大脑的一些区域。该肽在多种类型神经元中的广泛表达表明PTHRP可能在神经元生理学中发挥普遍作用。
A parathyroid hormone-related peptide (PTHRP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. While parathyroid hormone (PTH) gene expression appears to be limited to the parathyroid glands, PTHRP mRNA has been identified in a variety of normal tissues. To investigate the apparent expression of the PTHRP in the central nervous system, we examined extracts of whole rat brain for PTHRP bioactivity by measuring adenylate cyclase-stimulating activity (ACSA) in a PTH-sensitive assay. Extracts consistently contained ACSA and this activity was completely inhibited by a PTHRP antiserum but was unaffected by a PTH antiserum. ACSA was found in a number of anatomic subregions of rat brain, being greatest in the cortex and telencephalon. RNase protection analysis revealed PTHRP transcripts in total RNA prepared from whole rat brain and from the same anatomic subregions. By in situ hybridization histochemistry, we found that the highest levels of PTHRP gene expression occurred in neurons of the cerebral cortex, hippocampus, and cerebellar cortex. These studies demonstrate that both PTHRP mRNA and biological activity are present in a number of regions of rat brain. The widespread expression of this peptide by multiple types of neurons suggests that the PTHRP may play a general role in neuronal physiology.