Kim Kyongsong, Sanno Naoko, Arai Keiko, Takano Koji, Yasufuku-Takano Junko, Teramoto Akira, Shibasaki Tamotsu
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Clin Endocrinol (Oxf). 2003 Nov;59(5):630-6. doi: 10.1046/j.1365-2265.2003.01898.x.
Ghrelin and its receptor, growth hormone secretagogue (GHS) receptor (GHSR), are expressed in the normal pituitary gland and various types of pituitary adenoma. Somatic mutations in the subunit of Gs alpha protein (gsp), which led to a constitutive activation of adenylyl cyclase, are reported in GH-producing pituitary adenomas. We analysed the relationship between ghrelin mRNA and GHSR mRNA expression levels in gsp mutation-positive and -negative GH-producing pituitary adenomas.
Pituitary adenoma tissue was obtained at surgery from 20 patients with acromegaly.
The expression levels of human ghrelin mRNA and GHSR mRNA were quantified using a competitive RT-PCR method. To detect the gsp mutations, amplified Gs alpha subunit cDNA fragments were sequenced directly using RT-PCR method.
There was no significant difference in the expression of ghrelin mRNA between mutation-positive and -negative adenomas. The expression of GHSR mRNA was significantly lower in gsp mutation-positive than -negative adenomas. There was a significant negative correlation between the levels of ghrelin mRNA and GHSR mRNA expression in mutation-negative adenomas; no such correlation was found in mutation-positive adenomas.
These results suggest that GHSR mRNA expression is downregulated by ghrelin in gsp mutation-negative GH-producing pituitary adenomas, and that changes in intracellular signalling pathways in gsp mutation-positive GH-producing pituitary adenomas affect the expression of G protein-coupled receptors such as GHSR. The absence of negative correlation between ghrelin and GHSR expression might be induced by lowered GHSR expression in gsp mutation-positive GH-producing adenomas.
胃饥饿素及其受体，即生长激素促分泌素（GHS）受体（GHSR），在正常垂体及各类垂体腺瘤中均有表达。据报道，在分泌生长激素的垂体腺瘤中存在Gsα蛋白（gsp）亚基的体细胞突变，该突变导致腺苷酸环化酶的组成性激活。我们分析了gsp突变阳性和阴性的分泌生长激素的垂体腺瘤中胃饥饿素mRNA与GHSR mRNA表达水平之间的关系。
20例肢端肥大症患者在手术中获取垂体腺瘤组织。
采用竞争性逆转录聚合酶链反应（RT-PCR）方法定量检测人胃饥饿素mRNA和GHSR mRNA的表达水平。为检测gsp突变，使用RT-PCR方法直接对扩增的Gsα亚基cDNA片段进行测序。
突变阳性和阴性腺瘤之间胃饥饿素mRNA的表达无显著差异。GHSR mRNA在gsp突变阳性腺瘤中的表达显著低于突变阴性腺瘤。在突变阴性腺瘤中，胃饥饿素mRNA水平与GHSR mRNA表达之间存在显著负相关；而在突变阳性腺瘤中未发现这种相关性。
这些结果表明，在gsp突变阴性的分泌生长激素的垂体腺瘤中，胃饥饿素可下调GHSR mRNA的表达，并且gsp突变阳性的分泌生长激素的垂体腺瘤中细胞内信号通路的变化会影响G蛋白偶联受体如GHSR的表达。胃饥饿素与GHSR表达之间缺乏负相关可能是由于gsp突变阳性的分泌生长激素的腺瘤中GHSR表达降低所致。
