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Ghrelin mRNA and GH secretagogue receptor mRNA in human GH‐producing pituitary adenomas is affected by mutations in the α subunit of G protein
Author(s) -
Kim Kyongsong,
Sanno Naoko,
Arai Keiko,
Takano Koji,
YasufukuTakano Junko,
Teramoto Akira,
Shibasaki Tamotsu
Publication year - 2003
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2003.01898.x
Subject(s) - endocrinology , medicine , ghrelin , secretagogue , messenger rna , prolactin , receptor , biology , protein subunit , growth hormone secretagogue receptor , gnas complex locus , hormone , gene , genetics
Summary 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 α 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. patients 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 α 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. conclusion 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.