Ghrelin mRNA and GH secretagogue receptor mRNA in human GH-producing pituitary adenomas is affected by mutations in the alpha subunit of G protein.
OBJECTIVE
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.


METHODS
Pituitary adenoma tissue was obtained at surgery from 20 patients with acromegaly.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kim
Kyongsong
K
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan. kyongson@nms.ac.jp
Sanno
Naoko
N
Arai
Keiko
K
Takano
Koji
K
Yasufuku-Takano
Junko
J
Teramoto
Akira
A
Shibasaki
Tamotsu
T
D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D054440:Receptors, Ghrelin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone