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Effects of somatostatin-14 and the receptor-specific somatostatin analogs on chromogranin A and alpha-subunit (alpha-SU) release from "clinically nonfunctioning" pituitary adenoma cells incubated in vitro.

Abstract
The aim of the study was to examine the effect of somatostatin (SST) and its analogs on the release of chromogranin A (CgA) and alpha-subunit (alpha-SU) from clinically non-functioning pituitary adenomas incubated in vitro. Seven pituitary macroadenomas surgically removed were investigated. All of the tumors were diagnosed before surgery as non-functioning, but they expressed either gonadotropins or their subunits as detected by immunohistochemistry. Two tumors additionally expressed prolactin and growth hormone. All adenomas also expressed chromogranin A (CgA) and at least 3 of 5 subtypes of somatostatin receptors. The cells isolated from the examined tumors were exposed in vitro to either native SST-14 or the following receptor-specific SST analogs: BIM-23926 (agonist of sst1 receptor), BIM-23120 (agonist of sst2 receptor), BIM-23206 (agonist of sst5 receptor) and BIM23A387 (somatostatin/dopamine chimera). The concentration of CgA was measured by means of ELISA method and of alpha-SU was measured by an immunoradiometric method. It was found that the exposure on SST-14 resulted in the decrease of CgA and alpha-SU release from tumor cells in majority of samples, and the effect on CgA was positively correlated with the expression of sst3 and also with the sst2A/sst2B expressions ratio. The inhibitory effect of SST-14 on CgA and alpha-SU seems also to correlate negatively with the expression of sst2B. CgA inhibition also correlates positively with sst5 expression. Among the other compounds studied, only the sst2 agonist decreased the release in all the investigated samples. The remaining substances (agonists of sst1 and sst5 and SST/DA chimera) produced the divergent changes (increased or decreased release, depending on the sample). The data suggest that the inhibition of CgA (and possibly of alpha-SU) release by SST is mediated via subtypes sst2A, sst3 and sst5, whereas sst2B subtype may induce the opposite effect.
AuthorsM Pawlikowski, H Lawnicka, H Pisarek, J Kunert-Radek, M Radek, M D Culler
JournalJournal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 58 Issue 1 Pg. 179-88 (Mar 2007) ISSN: 0867-5910 [Print] Poland
PMID17440235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Chromogranin A
  • Glycoprotein Hormones, alpha Subunit
  • Luteinizing Hormone, beta Subunit
  • Receptors, Somatostatin
  • somatostatin receptor 3
  • somatostatin receptor sst2A
  • Human Growth Hormone
  • Somatostatin
  • somatostatin receptor 5
  • Prolactin
  • Follicle Stimulating Hormone
Topics
  • Adenoma (metabolism, pathology, physiopathology)
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal (pharmacology)
  • Biomarkers, Tumor (analysis, metabolism)
  • Chromogranin A (metabolism)
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follicle Stimulating Hormone (analysis)
  • Glycoprotein Hormones, alpha Subunit (metabolism)
  • Human Growth Hormone (analysis)
  • Humans
  • Immunohistochemistry
  • Immunoradiometric Assay
  • Luteinizing Hormone, beta Subunit (analysis)
  • Male
  • Middle Aged
  • Pituitary Neoplasms (metabolism, pathology, physiopathology)
  • Prolactin (analysis)
  • Receptors, Somatostatin (agonists, metabolism)
  • Somatostatin (analogs & derivatives, pharmacology)
  • Tumor Cells, Cultured

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