Relationship between the Expression of Growth Hormone-Releasing Hormone Receptor Gene and Endocrinologic Profiles in GH-Secreting Pituitary Adenomas / 대한내분비학회지

ABSTRACT

BACKGROUND: Growth hormone-releasing hormone (GHRH) plays a key role in the regulation of the proliferation and differentiation of somatomammotroph cells as well as secretion of GH. The actions of GHRH are mediated through the GHRH receptor (GHRH-R) that is a G protein coupled receptor with seven transmembrane domains. It has been demonstrated that alternative splicing occurs in the third cytoplasmic domain of rat and human GHRH-R mRNA, However, the clinical significance of the altemative splicing remains to be unsolved. To find an insight into the clinical significance, we investigate the correlation between the GHRH-R gene expression and a variety of clinical clinical and endocrinological findings in 11 acromegalic patients. METHODS: Eleven acromegalic patients (3 males and 8 females, mean age 43.5 years) were included in this study. Six endocrine tests were carried out to evaluate the GH seeretory function of tumors. Invasiveness of tumors were evaluated by preoperative MRI findings on the basis of Hardys classification. Sequence the gsp oncogene and estimate the GHRH-R gene expression by RT-PCR and in vitro transcription. RESULTS: Three different sized cDNA fragments, 250 bp, 700 bp and 810 bp, were found after RT-PCR. The amount of 250 bp fragment was higher than those of the other two fragments. The clinical findings (age, size, GH level, frequency of paradoxical response to TRH or GnRH, octreotide response, hypothalamic somatostatinergic activity) of the group with high expression of the 250 bp fragment did not significantly differ from those of the group with low expression. The GHRH-R gene expression of tumors with gsp oncogene did not significantly differ from that of tumors without gsp oncogene. CONCLUSION: These results suggest that the expression of GHRH-R gene may not be an important determinant for tumor growth, and the lower GH response to GHRH of tumors with gsp oncogene may not be attributed to the lower expression of GHRH-R gene. The expression of GHRH-R is likely to be regulated by a certain property of tumors for GH secretion and growth.