A Polymorphism in the Growth Hormone (GH)-Releasing Hormone (GHRH) Receptor Gene Is Associated with Elevated Response to GHRH by Human Pituitary Somatotrophinomas in Vitro
| Autor: | Michael Buchfelder, David R. Poyner, Eric F. Adams, Hedwig Symowski |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Receptors Neuropeptide endocrine system medicine.medical_specialty DNA Mutational Analysis Biophysics Biology Growth Hormone-Releasing Hormone Polymorphism Single Nucleotide Biochemistry Loss of heterozygosity Germline mutation Receptors Pituitary Hormone-Regulating Hormone Internal medicine Cyclic AMP Tumor Cells Cultured medicine Humans Pituitary Neoplasms Allele Threonine Codon Molecular Biology Gene Alanine Base Sequence Human Growth Hormone Cell Biology Middle Aged Growth hormone secretion Endocrinology Acromegaly Female hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Biochemical and Biophysical Research Communications. 275:33-36 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.2000.3247 |
| Popis: | A previous study has suggested that a G to A base change at position 169 of the GHRH-receptor gene in human somatotrophinomas is a mutation and confers hypersensitivity to GHRH. The alternative base converts codon 57 from GCG to AGC, resulting in replacement of alanine (Ala) with threonine (Thr). In the present study, two of five human GH-secreting somatotrophinomas were found to possess the codon 57 AGC sequence. The GCG allele was also detected, indicating heterozygosity. However, the patients' normal blood-derived DNA also yielded the same sequence pattern, indicating that the Ala=> Thr amino acid change is a normal polymorphism, and not a somatic mutation. Nevertheless, in vitro, the tumors possessing the Ala=> Thr amino acid change responded very strongly to GHRH in terms of cAMP formation, being increased 40- and 200-fold, in comparison to the 2-fold increases by tumors without the alternative GHRH-receptor sequence. Likewise, the in vitro response of GH secretion to GHRH was elevated. One of the two tumors with the alternative Thr residue, and the highest responder to GHRH, possessed a gsp muration, despite the fact that these defects are thought to reduce responsiveness to GHRH. These results fail to confirm that the GCG => AGC at codon 57 of the GHRH-receptor gene is a mutation, but do support the concept that the alternative form with Thr confers increased sensitivity to GHRH. (C) 2000 Academic Press. |
| Databáze: | OpenAIRE |
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