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Regulation of Calcitonin Secretion and Calcitonin Gene Expression

  • Chapter
Medullary Thyroid Carcinoma

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 125))

Abstract

Medullary thyroid carcinoma (MTC) is a tumor of the calcitonin (CT)-secreting cells (C-cells or parafollicular cells). During embryogenesis C-cells migrate from the neural crest to the last branchial pouch and ultimately into the thyroid. In contrast to the follicular cells of the thyroid gland that produce the thyroid hormones under the control of thyroid-stimulating hormone (TSH), the C-cells secrete CT and related peptides under different control systems (Deftos and Roos 1989). CT helps to maintain the calcium homeostasis and as a feedback, physiological changes in blood-calcium concentration directly regulate CT secretion. In addition, 1,25 (OH)2D3 is involved in CT secretion and synthesis. CT release is also closely tied to feeding and gastrointestinal activity; gastrointestinal hormonal factors including gastrin, cholecystokinin (CCK), and glucagon participate in promoting CT release. Moreover neuroendocrine factors may be involved in the control of CT secretion. β-Adrenergic agonists stimulate CT secretion, while α-adrenergic agonists and dopamine inhibit it, which suggests a participation of the autonomic nervous system in the regulation of CT secretion. Somatostatin appears to have a paracrine or autocrine regulatory function as it is secreted by C-cells and it is able to inhibit CT secretion. While these phenomena can be studied in vivo, emphasizing their physiological relevance, the cellular and molecular mechanisms underlying regulation of CT secretion, synthesis, and transcription can only be studied in in vitro systems. The available in vitro systems include rat thyroid explants (Cooper et al. 1977), primary cell cultures of MTC (Raue et al. 1989), and permanent C-cell carcinoma cell lines (human TT: Leong et al. 1981; rMTC 6–23: Gagel et al. 1980). Cellular signaling processes thought to be involved in initiation of C-cell neoplasia and subsequent cellular changes during tumor progression are activation of adenylate cyclase, protein kinase C, and oncogenes.

This work was supported by a research grant from the Deutsche Forschungsgemeinschaft (Ra 327/1–4) and a DFG fellowship to Hans Scherübl.

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  1. H. Scherübl

    Present address: Abteilung für Innere Medizin/Gastnoenterologie, Freie Universität Berlin, Hindenburgdamm 30, 1000, Berlin 45, Germany

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  1. Abteilung für Innere Medizin I - Endokrinologie und Stoffwechsel, Universität Heidelberg, Luisenstraße 5, W-6900, Heidelberg 1, Germany

    F. Raue, A. Zink & H. Scherübl

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    Friedhelm Raue

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Raue, F., Zink, A., Scherübl, H. (1992). Regulation of Calcitonin Secretion and Calcitonin Gene Expression. In: Raue, F. (eds) Medullary Thyroid Carcinoma. Recent Results in Cancer Research, vol 125. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84749-3_1

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