Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells

M. E. Sunday, H. J. Wolfe, Eliot Spindel, W. W. Chin, E. R. Spindel

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Gastrin-releasing peptide (GRP), the mammalian homolog of bombesin, is often studied as a prototypic neuroregulatory hormone and growth factor, but its own regulation and physiological roles remain to be fully defined. We now demonstrate that the GRP gene is expressed in human thyroidal calcitonin (CT)-containing neuroendocrine cells (C-cells) in an ontogenic pattern similar to its expression in pulmonary neuroendocrine cells and is also expressed at high levels in C-cell hyperplasias and neoplasias (medullary carcinomas of the thyroid). Mean GRP-like immunoreactivity is 20 times higher in 3-week-old to 5-month-old infants than in normal adults, with six of seven infants having GRP levels 6- to 67-fold higher than those in normal adults, the highest levels occurring at 2-2.5 months. CT levels are about 100 times greater than GRP levels at all time intervals, with levels of GRP and CT being linearly correlated (r = 0.98). By RNA blot analysis, GRP mRNAs are increased in neonatal thyroids compared to adult thyroids. In situ hybridization and immunoperoxidase analyses localize GRP mRNAs and peptide to a majority of C-cells in fetuses and neonates, but to only 5-18% of C-cells in normal adults. The majority of developing C-cells have a dendritic morphology, suggesting a paracrine role, although this morphology is not observed in adult C-cells. In addition, for unknown reasons, an increased percentage of C-cells positive for GRP occurs in normal thyroid adjacent to GRP-negative follicular adenomas and papillary carcinomas, an association that we term perineoplastic. We hypothesize that GRP gene expression may play a role in both normal and neoplastic growth processes.

Original languageEnglish (US)
Pages (from-to)1551-1558
Number of pages8
JournalEndocrinology
Volume122
Issue number4
StatePublished - 1988
Externally publishedYes

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Gastrin-Releasing Peptide
Neuroendocrine Cells
Thyroid Gland
Gene Expression
Calcitonin
Neoplastic Processes
Bombesin
Messenger RNA
Papillary Carcinoma
Adenoma
Hyperplasia
In Situ Hybridization
Intercellular Signaling Peptides and Proteins
Fetus

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Sunday, M. E., Wolfe, H. J., Spindel, E., Chin, W. W., & Spindel, E. R. (1988). Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells. Endocrinology, 122(4), 1551-1558.

Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells. / Sunday, M. E.; Wolfe, H. J.; Spindel, Eliot; Chin, W. W.; Spindel, E. R.

In: Endocrinology, Vol. 122, No. 4, 1988, p. 1551-1558.

Research output: Contribution to journalArticle

Sunday, ME, Wolfe, HJ, Spindel, E, Chin, WW & Spindel, ER 1988, 'Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells', Endocrinology, vol. 122, no. 4, pp. 1551-1558.
Sunday, M. E. ; Wolfe, H. J. ; Spindel, Eliot ; Chin, W. W. ; Spindel, E. R. / Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells. In: Endocrinology. 1988 ; Vol. 122, No. 4. pp. 1551-1558.
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