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Low Levels of Raf Kinase Inhibitory Protein in Growth Hormone-Secreting Pituitary Adenomas Correlate with Poor Response to Octreotide Treatment
- Source :
- The Journal of Clinical Endocrinology & Metabolism. 93:1211-1216
- Publication Year :
- 2008
- Publisher :
- The Endocrine Society, 2008.
-
Abstract
- Excessive GH production by pituitary tumors causes acromegaly. Medical treatment of acromegaly with somatostatin analogs (SMSs), like octreotide, is well established, but the clinical effect is variable. One mechanism for octreotide effect is inhibition of the MAPK signaling pathway after binding to the G protein-coupled somatostatin receptor. Nonphosphorylated Raf kinase inhibitory protein (RKIP) binds to and inhibits Raf1 kinase, and thereby attenuates MAPK signaling, whereas phosphorylated RKIP inhibits G protein receptor internalization and degradation due to inhibition of G protein receptor kinase 2.Our objective was to study RKIP levels in pituitary somatotroph adenomas, and relate them to clinical characteristics and response to octreotide treatment in patients with acromegaly.RKIP level was analyzed by Western blot of proteins extracted from somatotroph tumors frozen a short time after surgery in 51 patients with active acromegaly. An acute somatostatin test was performed in 46 of the patients, and in 21 the IGF-I level before and 6 months after SMS treatment was available.The adenoma RKIP level correlated significantly to both the acute and the long-term octreotide responses on serum levels of GH and IGF-I, respectively. In multiple regression analyses, the RKIP level was a significant determinant for both the GH reduction in the acute test and the IGF-I reduction after approximately 6 months.The RKIP level in somatotroph adenomas seems to be important for the clinical effect of SMS treatment, in which low levels of RKIP correlate to poor clinical response to SMSs.
- Subjects :
- Adenoma
Adult
Male
medicine.medical_specialty
Antineoplastic Agents, Hormonal
Somatotropic cell
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Octreotide
Phosphatidylethanolamine Binding Protein
Biology
Biochemistry
Endocrinology
Internal medicine
Acromegaly
medicine
Humans
Somatostatin receptor 2
Receptors, Somatostatin
G protein-coupled receptor
Somatostatin receptor
Biochemistry (medical)
Pituitary tumors
Middle Aged
medicine.disease
Somatostatin
Female
Growth Hormone-Secreting Pituitary Adenoma
medicine.drug
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....afad908954b1b795fa8b0f4532567e27