Genetic Diagnosis in Pituitary Tumors

垂体瘤的基因诊断

• 批准号: 11671391
• 负责人: ABE Taku
• 金额: $ 2.3万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671391/
• 关键词: Human; Pituitary gland; Prolaction-releasing peptide; Pituitary adenoma; Receptor; Immunohistochemistry; ACTH; Reverse transcription-polymerase chain reaction; 遺伝子診断; プロラクチン放出因子

Prolactin-releasing peptide (PrRP) and its receptor (PrRP-R) have recently been characterized and cloned. PrRP functions as a prolactin-secreting factor through binding with PrRP-R, which is extensively expressed in the human pituitary. However, its other biological functions remain unknown.We studied the expression of PrRP-R in human pituitary adenomas. Pituitary adenomas were collected from 13 patients by transsphenoidal resection. Six patients had prolactin-secreting adenomas, three had ACTH-secreting adenomas, one had a GH-secreting adenoma, and three had nonsecreting adenomas. All pituitary adenomas examined by RT-PCR analysis expressed PrRP-R. When semiquantitative competitive PCR was performed to determine the relative amounts of the PrRP-R mRNA expression level, there was no correlation between plasma prolactin levels and PrRPR expression levels. These results suggest that the plasma prolactin level is regulated by means other than signal transduction through PrRP-R activation.Using immunohistochemistry, we examined the distribution of the PrRP receptor in various human tissues, as well as the precise localization of the PrRP receptor in the human normal pituitary. Among various tissues examined, PrRP receptor immunopositive cells were detected only in the pituitary gland. A double immunohistochemical procedure was used to examine PrRP receptor positive cells from 10 normal human pituitary glands and it was determined that all PrRP receptor positive cells are also positive for ACTH but negative for PRL. Neither GH, j3 TSH, j3 FSH, 13 LH or a subunit positive cells tested positive for the presence of PrRP receptors. Thus, we suggest that PrRP receptor and probably PrRP may play a regulatory role in ACTH secretion, rather than in the release of PRL from the human anterior pituitary. This is the first report to demonstrate colocalization of the PrRP receptor and ACTH by immunohistochemistry.

催乳素释放肽（Prolactin-releasing peptide，PrRP）及其受体（PrRP-R）是近年来发现并克隆的一种催乳素释放肽。PrRP通过与PrRP-R结合而作为催乳素分泌因子发挥作用，PrRP-R在人垂体中广泛表达。我们研究了PrRP-R在人垂体腺瘤中的表达。收集了13例经蝶窦切除的垂体腺瘤。6例患者有催乳素分泌腺瘤，3例ACTH分泌腺瘤，1例GH分泌腺瘤，3例非分泌腺瘤。RT-PCR分析所有垂体腺瘤均表达PrRP-R。当进行半定量竞争性PCR，以确定相对量的PrRP-R mRNA表达水平，血浆催乳素水平和PrRPR表达水平之间没有相关性。这些结果表明，血浆催乳素水平的调节手段以外的信号转导通过PrRP-R activation.Using免疫组织化学，我们研究了PrRP受体在各种人体组织中的分布，以及PrRP受体在人正常垂体的精确定位。在检查的各种组织中，仅在垂体中检测到PrRP受体免疫阳性细胞。用免疫组化双重法检测了10例正常人垂体PrRP受体阳性细胞，发现所有PrRP受体阳性细胞均为ACTH阳性而PRL阴性。GH、α 3 TSH、α 3 FSH、α 3 LH或α亚单位阳性细胞均未检测到PrRP受体的存在。因此，我们认为，PrRP受体，可能PrRP可能发挥调节作用的ACTH分泌，而不是在释放PRL从人垂体前叶。这是第一份报告，证明共定位的PrRP受体和促肾上腺皮质激素的免疫组织化学。

项目成果

Takumi Abe: "Mucocele-like formation leading to neurological symptoms in prolactin-secreting pituitary adenomas under dopamine agonist therapy"Surgical Neurology. 52. 274-279 (1999)

Takumi Abe：“在多巴胺激动剂治疗下，分泌催乳素的垂体腺瘤中出现粘液囊肿样形成导致神经系统症状”，《神经外科》。

Takumi Abe: "Does prolactin-releasing peptide receptor regulate prolactin-secretion in human pituitary adenomas?"Neuroscience Letters. 29・1. 159-162 (2000)

Takumi Abe：“催乳素释放肽受体调节人垂体腺瘤中的催乳素分泌吗？”《神经科学快报》29・1（2000）。

Takumi Abe: "Silent mixed corticotroph and somatotroph macroadenomas presenting with pituitary apoplexy"Acta Neuropathologica. 102(5). 435-440 (2001)

Takumi Abe：“伴有垂体中风的无症状混合性促肾上腺皮质激素和生长激素大腺瘤”《神经病理学报》。

Takumi Abe: "Cellular Localization of Prolactin-releasing Peptide Receptors in the Human Pituitary"Neuroendocrinology, in press.

Takumi Abe：“人类垂体中催乳素释放肽受体的细胞定位”神经内分泌学，正在出版。

Takumi Abe, et al: "Metastatic skull tumors from cancers associated with subcutaneous mass lesions"Brain and Nerve (Tokyo). 51(4). 353-359 (1999)

Takumi Abe 等人：“来自与皮下肿块病变相关的癌症的转移性颅骨肿瘤”《大脑和神经》（东京）。