ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2007) 13 S1 
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The ever expanding role of somatostatin receptors in endocrine disease

Steven WJ Lamberts & Leo J Hofland

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Studies on the distribution of Somatostatin Receptor (sst)-subtypes on endocrine tumors, the development of sst-subtype specific analogues, the elucidation of phenomena like receptor desensitization and ligand-receptor internalization, and the potential consequences (and reversal) of the epigenetic silencing of sst offer new diagnostic and therapeutic modalities in endocrine diseases:

1. apart from sst2 activation, Somatostatin analogues targeting sst5 on part of GH-secreting pituitary adenomas increase the number of acromegalic patients that can be effectively treated medically.

2. corticotrophinomas differentially express sst5, dopamine2-receptors, as well as the potential of sst2, making effective medical therapy of Cushing’s disease a reality.

3. sst2 visualization of (neuro)-endocrine tumors not only provides insight in the localization of the primary tumor, but also of previously unknown distant metastases, and predicts response to Somatostatin analogue therapy.

4. the mechanism(s) of escape of hormone secretion and tumor growth control from Somatostatin analogue treatment in patients with malignant carcinoids and endocrine pancreatic tumors often includes disconnection of sst from its intracellular signaling systems.

5. the higher the number of sst, the better the success of targeted radiotherapy with somatostatin analogue-coupled β-emitting radionuclides.

6. (temporary/transient) upregulation of sst expression on sst-positive tumors is a new approach. In some instances hypermethylation of sst on neuroendocrine cancers can be reversed by epigenetic drugs.

Conclusions: Expression of sst on a variety of endocrine tumors in man allows successful diagnostic and therapeutic interventions. Building upon physiologic processes like sst-subtype expression on (tumor)-cell membranes, ligand-receptor activation of intracellular signaling systems which regulate hormone secretion, ligand-receptor internationalization of radionuclide-coupled analogues and manipulation by up- an down-regulation of sst on human (neuro-)endocrine tumors makes this field an example of practical molecular medicine.

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