Igarashi-Migitaka Junko, Yamada Shozo, Hara Masayuki, Sano Toshiaki, Ozawa Yasunori, Ohtani-Kaneko Ritsuko, Hirata Kazuaki
Department of Anatomy, St. Marianna University School of Medicine, Sugao, Kawasaki 216-8511, Japan.
Endocr J. 2003 Aug;50(4):459-67. doi: 10.1507/endocrj.50.459.
Thyrotropin releasing hormone receptor 1 (TRHR1) and 2 (TRHR2) mRNAs were examined using reverse transcription polymerase chain reaction (RT-PCR). These data were then correlated with endocrinological and histological characteristics in 65 human pituitary adenomas including one non tumorous pituitary gland, to clarify the role of TRHR1 and 2 gene expression in human pituitary adenomas, especially as it relates to the paradoxical stimulatory effects of TRH found in pituitary adenomas. TRHR mRNA was not identified in four ACTH cell adenomas, whereas TRHR mRNA expression was found in 12/23 acromegaly specimens, 7/8 prolactinomas, 3/3 TSH cell adenomas, and 22/27 clinically nonfunctioning adenomas. Specimens obtained from patients expressing the TRHR gene were found to express TRHR1 and TRHR2 or TRHR1 alone, whereas no cases were identified in which TRHR2 alone was expressed. In examining the relationship between GH, PRL, TSH, or gonadotropin subunit response to TRH administration and TRHR gene expression, TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without paradoxical GH response to TRH (non-responder), whereas TRHR genes were shown to be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH (responders) (chi2 = 11.73, p = 0.0009). However, there was no significant correlation between TRHR gene expression and responsiveness to PRL or gonadotropins to TRH administration in PRL cell adenomas (chi2 = 0.16, p = 0.87) or gonadotroph cell adenomas (chi2 = 0.0006, p = 1), respectively. We concluded that the existence of the TRH receptor in adenoma cells plays an important role in the paradoxical GH response to TRH administration in GH cell adenomas. It should be noted that the PRL response to TRH in prolactinoma or an abnormal response of gonadotropin and/or its subunits to TRH in gonadotroph cell adenomas is considered to be due to a mechanism other than direct TRH action in adenoma cells. However, further studies are required to elucidate the role of TRHR2 in pituitary adenomas.
采用逆转录聚合酶链反应（RT-PCR）检测促甲状腺激素释放激素受体1（TRHR1）和2（TRHR2）的信使核糖核酸（mRNA）。然后将这些数据与65例人垂体腺瘤（包括1个非肿瘤性垂体）的内分泌学和组织学特征相关联，以阐明TRHR1和2基因表达在人垂体腺瘤中的作用，尤其是其与垂体腺瘤中发现的促甲状腺激素释放激素（TRH）的矛盾刺激作用的关系。在4例促肾上腺皮质激素（ACTH）细胞腺瘤中未检测到TRHR mRNA，而在12/23例肢端肥大症标本、7/8例催乳素瘤、3/3例促甲状腺激素（TSH）细胞腺瘤和22/27例临床无功能腺瘤中发现了TRHR mRNA表达。从表达TRHR基因的患者获取的标本中，发现表达TRHR1和TRHR2或仅表达TRHR1，而未发现仅表达TRHR2的病例。在研究生长激素（GH）、催乳素（PRL）、TSH或促性腺激素亚基对TRH给药的反应与TRHR基因表达之间的关系时，发现10例对TRH无矛盾GH反应的GH细胞腺瘤（无反应者）中有9例不存在TRHR mRNA，而12例对TRH有矛盾GH反应的GH细胞腺瘤（反应者）中有10例显示TRHR基因表达（卡方=11.73，p=0.0009）。然而，在催乳素细胞腺瘤中，TRHR基因表达与PRL对TRH给药的反应性之间无显著相关性（卡方=0.16，p=0.87），在促性腺激素细胞腺瘤中，TRHR基因表达与促性腺激素对TRH给药的反应性之间也无显著相关性（卡方=0.0006，p=1）。我们得出结论，腺瘤细胞中TRH受体的存在在GH细胞腺瘤对TRH给药的矛盾GH反应中起重要作用。应当指出，催乳素瘤中PRL对TRH的反应或促性腺激素细胞腺瘤中促性腺激素和/或其亚基对TRH的异常反应被认为是由腺瘤细胞中TRH直接作用以外的机制引起的。然而，需要进一步研究以阐明TRHR2在垂体腺瘤中的作用。
