Skinner M M, Nass R, Lopes B, Laws E R, Thorner M O
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
J Clin Endocrinol Metab. 1998 Dec;83(12):4314-20. doi: 10.1210/jcem.83.12.5307.
The GH secretagogue (GHS) receptor (GHS-R) has been characterized and cloned. It is a member of a family of seven transmembrane receptors and is closely related to the neurotensin and TRH receptors. To determine the expression of this receptor in normal anterior pituitary and in 24 human pituitary adenomas, we analyzed GHS-R messenger ribonucleic acid (mRNA) using a RT-PCR assay. We found that normal human pituitary was positive for the GHS-R signal. In addition, all GH-secreting adenomas and the one TSH-secreting adenoma demonstrated the presence of GHS-R mRNA. Three of four ACTH-secreting tumors and three of nine gonadotroph adenomas were also positive for the GHS-R mRNA. To determine the amounts of GHS-R mRNA in normal pituitary and in representative tumors, semiquantitative competitive PCR was performed. We determined that normal pituitary had approximately 750 molecules/L GHS-R mRNA. The acromegalic tumor had approximately 1.5 x 10(5) molecules/L, and the TSH-secreting tumor had approximately 7.5 x 10(3) molecules/L. Other tumor types contained considerably less, with the ACTH-secreting and gonadotroph tumors expressing 7.5 x 10(2) and 3 x 10(2) GHS-R mRNA molecules/L, respectively. These results suggest that GH- and TSH-producing adenomas express GHS-R mRNA at levels 200 and 10 times higher, respectively, than the normal pituitary, and that this receptor expression may be involved in the pathogenesis and growth of these pituitary adenomas.
生长激素促分泌素(GHS)受体(GHS-R)已被鉴定和克隆。它是七跨膜受体家族的一员,与神经降压素和促甲状腺激素释放激素受体密切相关。为了确定该受体在正常垂体前叶和24例人类垂体腺瘤中的表达,我们使用逆转录聚合酶链反应(RT-PCR)分析了GHS-R信使核糖核酸(mRNA)。我们发现正常人类垂体GHS-R信号呈阳性。此外,所有分泌生长激素的腺瘤和1例分泌促甲状腺激素的腺瘤均显示存在GHS-R mRNA。4例分泌促肾上腺皮质激素的肿瘤中有3例以及9例促性腺激素腺瘤中有3例GHS-R mRNA也呈阳性。为了确定正常垂体和代表性肿瘤中GHS-R mRNA的量,进行了半定量竞争性PCR。我们确定正常垂体中约有750个分子/升GHS-R mRNA。肢端肥大症肿瘤约有1.5×10⁵个分子/升,分泌促甲状腺激素的肿瘤约有7.5×10³个分子/升。其他肿瘤类型所含的量要少得多,分泌促肾上腺皮质激素的肿瘤和促性腺激素肿瘤分别表达7.5×10²和3×10²个GHS-R mRNA分子/升。这些结果表明,分泌生长激素和促甲状腺激素的腺瘤表达GHS-R mRNA的水平分别比正常垂体高200倍和10倍,并且这种受体表达可能参与这些垂体腺瘤的发病机制和生长。