Abstract | OBJECTIVE: Currently, there is no effective medical treatment for patients with pituitary-dependent Cushing's disease. A novel somatostatin (SS) analogue, named SOM230, with high binding affinity to SS receptor subtypes sst(1), sst(2), sst(3) and sst(5) was recently introduced. We compared the in vitro effects of the sst(2)-preferring SS analogue octreotide (OCT) and the multi- ligand SOM230 on ACTH release by human and mouse corticotroph tumour cells. METHODS: RESULTS:
Corticotroph adenomas expressed predominantly sst(5) mRNA (six out of six adenomas), whereas sst(2) mRNA expression was detected at significantly lower levels. In a 72 h incubation with 10 nmol/l SOM230, ACTH release was inhibited in three out of five cultures (range -30 to -40%). Ten nmol/l OCT slightly inhibited ACTH release in only one of five cultures (- 28%). In AtT20 cells, expressing sst(2), sst(3) and sst(5), SOM230 inhibited ACTH secretion with high potency (IC(50) 0.2 nmol/l). Dexamethasone (10 nmol/l) pre-treatment did not influence the sensitivity of the cells to the inhibitory effect of SOM230, suggesting that sst(5) is relatively resistant to negative control by glucocorticoids. CONCLUSIONS:
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Authors | Leo J Hofland, Joost van der Hoek, Richard Feelders, Maarten O van Aken, Peter M van Koetsveld, Marlijn Waaijers, Diana Sprij-Mooij, Christian Bruns, Gisbert Weckbecker, Wouter W de Herder, Albert Beckers, Steven W J Lamberts |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 152
Issue 4
Pg. 645-54
(Apr 2005)
ISSN: 0804-4643 [Print] England |
PMID | 15817922
(Publication Type: Journal Article)
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Chemical References |
- Glucocorticoids
- RNA, Messenger
- Receptors, Somatostatin
- Somatostatin
- somatostatin receptor 5
- Adrenocorticotropic Hormone
- pasireotide
- Octreotide
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Topics |
- Adenoma
(metabolism)
- Adrenocorticotropic Hormone
(metabolism)
- Animals
- Gene Expression
(drug effects)
- Glucocorticoids
(pharmacology)
- Humans
- Mice
- Octreotide
(pharmacology)
- Pituitary Neoplasms
(metabolism)
- RNA, Messenger
(analysis)
- Receptors, Somatostatin
(genetics, physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Somatostatin
(analogs & derivatives, pharmacology)
- Tumor Cells, Cultured
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