Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas.
Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas.
复制标题
人垂体腺瘤中垂体腺苷酸环化酶激活多肽（PACAP）结合位点和 PACAP/血管活性肠多肽受体表达。
DOI：
10.1016/s0002-9440(10)65693-3
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Lloyd,RV
中科院分区：
文献类型：
--
作者：
Oka,H;Jin,L;Reubi,JC;Qian,X;Scheithauer,BW;Fujii,K;Kameya,T;Lloyd,RV
垂体腺苷酸环化酶激活多肽（PACAP）通过与垂体细胞上的PACAP受体相互作用刺激几种垂体前叶激素的释放。为了进一步了解PACAP及其受体在垂体腺瘤中的分布和可能的调节作用，我们采用受体放射自显影技术研究了血管活性肠肽（VIP）和PACAP结合位点的表达，采用逆转录聚合酶链反应（RT-PCR）、原位杂交、和催化报道沉积原位杂交（CARD-ISH）分析。PACAP mRNA在正常人下丘脑中表达，作为阳性对照，而在垂体腺瘤中不表达。受体放射自显影显示PACAP I型和II型结合位点在所有组的垂体腺瘤，泌乳素腺瘤除外。促性腺激素细胞腺瘤和空细胞腺瘤中的水平最高。RT-PCR结果显示PVR-2 mRNA在正常垂体和所有垂体腺瘤中均有表达，而PVR-1和PVR-3 mRNA在除大多数泌乳素腺瘤外的所有垂体腺瘤中均有表达。传统的原位杂交研究地高辛标记的探针显示，在大多数组织中PVR-1，-2和-3 mRNA的弱染色。CARD-ISH技术，增加了原位杂交方法的灵敏度，也揭示了PVR-2 mRNA的表达在所有腺瘤，而PVR-1和-3 mRNA的检测几乎在所有的腺瘤除了泌乳素瘤。PACAP mRNA的存在下丘脑，但不是在正常的垂体前叶或垂体腺瘤，和差异表达的PVRs在腺瘤中表明选择性调节内分泌和旁分泌作用的PACAP在正常和肿瘤性垂体前叶细胞。
Pituitary adenylate-cyclase-activating polypeptide (PACAP) stimulates release of several anterior pituitary hormones by interacting with PACAP receptors on pituitary cells. To learn more about the distribution and possible regulatory roles of PACAP and its receptors in human pituitary adenomas, we investigated the expression of vasoactive intestinal polypeptide (VIP) and PACAP binding sites using receptor autoradiography, PACAP and PACAP/VIP receptor (PVR) mRNAs by reverse transcription polymerase chain reaction (RT-PCR), conventional in situhybridization, and catalyzed reporter deposition in situ hybridization (CARD-ISH) analyses. PACAP mRNA was expressed in normal human hypothalamus, which was used as a positive control, but not in pituitary adenomas. Receptor autoradiography showed PACAP types I and II binding sites in all groups of pituitary adenomas, except prolactinomas. The highest levels were present in gonadotroph and null cell adenomas. PVR-2 mRNA was expressed in normal pituitaries and in all groups of pituitary adenomas by RT-PCR, whereas PVR-1 and -3 mRNAs were expressed in all groups of pituitary adenomas, except for most prolactinomas. Conventional in situ hybridization studies with digoxigenin-labeled probes demonstrated weak staining for PVR-1, -2, and -3 mRNAs in most tissues. The CARD-ISH technique, which increased the sensitivity of the in situ hybridization method, also revealed PVR-2 mRNA expression in all adenomas, whereas PVR-1 and -3 mRNAs were detected in nearly all adenomas except for prolactinomas. The presence of PACAP mRNA in the hypothalamus, but not in normal anterior pituitary or in pituitary adenomas, and the differential expression of PVRs in adenomas indicate a selective regulatory endocrine and paracrine role of PACAP in normal and neoplastic anterior pituitary cells.