J Korean Soc Endocrinol.
1999 Jun;14(2):241-254.
Relationship between the Expression of Growth Hormone-Releasing Hormone Receptor Gene and Endocrinologic Profiles in GH-Secreting Pituitary Adenomas
Abstract
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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.