Abstract |
We tested effects of selective somatostatin receptor 2 (SST2) agonist BIM-23120, SST5 agonist BIM-23206 and chimeric somatostatin- dopamine molecules (SRIF/DA) BIM-23A760 and BIM-23A761 on GH and PRL secretion and gene expression in human GH/PRL-secreting pituitary tumors in vitro. In "responders" group BIM-23120 suppressed GH levels by 26±4%, BIM-23206 by 31±5%, BIM-23A760 by 23±4%, BIM-23A761 by 39±8% and D(2)-dopamine agonist BIM-53097 by 31±5%. Using real-time PCR we demonstrated that GH inhibition was not accompanied by decreased GH mRNA levels. PRL secretion was inhibited by BIM-23A760 (29±5%), BIM-23A761 (34±4%), BIM-23206 (26±4%) and BIM-53097 (36±2%). SRIF/DA and BIM-53097 also suppressed PRL mRNA levels. Concluding, SST2 and SST5 agonists and SRIF/DA inhibit GH secretion, but do not suppress GH gene transcription. SRIF/DA and BIM-53097 inhibit both PRL secretion and PRL gene expression. SST5 agonist inhibits PRL secretion, but does not suppress PRL gene expression. D(2) affinity is crucial in SRIF/DA action on PRL gene expression.
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Authors | Anna Gruszka, Michael D Culler, Shlomo Melmed |
Journal | Molecular and cellular endocrinology
(Mol Cell Endocrinol)
Vol. 362
Issue 1-2
Pg. 104-9
(Oct 15 2012)
ISSN: 1872-8057 [Electronic] Ireland |
PMID | 22705877
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- BIM 23120
- BIM 23206
- BIM-23A761
- Receptors, Somatostatin
- Human Growth Hormone
- Somatostatin
- Prolactin
- TBR-760
- Dopamine
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Topics |
- Adenoma
(drug therapy, metabolism, pathology)
- Adult
- Aged
- Dopamine
(analogs & derivatives, pharmacology)
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Human Growth Hormone
(genetics, metabolism)
- Humans
- Male
- Middle Aged
- Pituitary Neoplasms
(drug therapy, metabolism, pathology)
- Prolactin
(genetics, metabolism)
- Receptors, Somatostatin
(agonists)
- Somatostatin
(analogs & derivatives, pharmacology)
- Transcription, Genetic
(drug effects)
- Tumor Cells, Cultured
(drug effects)
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