Substantial production of ghrelin by a human medullary thyroid carcinoma cell line

Ghrelin, an endogenous ligand for the GH secretagogue receptor, is a novel acylated peptide produced in the gastrointestinal endocrine cells as well a s neuroendocrine cells in the hypothalamus. The Ser(3) residue of ghrelin i s modified by n-octanoic acid, a modification necessary for hormonal activi ty. Human medullary thyroid carcinoma is known to produce a variety of gast rointestinal and neuroendocrine peptides. In the present study we investiga ted ghrelin production in the thyroid gland, especially in human medullary thyroid carcinoma. PCR amplification demonstrated prepro-ghrelin gene trans cripts in normal human thyroid tissue and two medullary thyroid carcinoma c ell lines (human TT cells and rat 6.23 cells), but not in a rat thyroid fol licular cell line. TT cells showed the expression of prepro-ghrelin mRNA of about 0.6 kb by Northern blot analysis. Furthermore, production of ghrelin in TT cells was demonstrated by RIA and immunocytochemistry. Accumulation of des-n-octanoyl ghrelin in the cultured medium of the cells was confirmed . Finally, human medullary thyroid carcinoma surgical specimens showed sign ificantly higher des-n-octanoyl ghrelin contents than normal thyroid tissue s. In conclusion, we revealed that ghrelin was produced by the human thyroi d parafollicular carcinoma cell line, TT cells. These findings suggest that ghrelin is produced in the thyroid C cells as well as in medullary thyroid carcinoma and may provide opportunities to investigate its physiological r ole in the thyroid gland.