Calcitonin gene-related peptide in the human thyroid, pituitary and brain

Abstract

Alternative splicing of rat calcitonin (CT) gene transcripts resulting in the production of calcitonin gene-related peptide (CGRP) in neural tissue and of CT in the thyroid has been proposed by Rosenfeld et al. (1983b). We have recognized CGRP- and CT-like peptides in extracts of the human brain, pituitary and thyroid using a combination of gel filtration analysis and HPLC, and specific RIAs. Immunoreactive CGRP was estimated in a heterologous RIA using 125I-labelled rat CGRP as ligand and antibodies raised to the rat hormone, and human CT in a homologous RIA. The levels of CGRP and CT are measured against synthetic rat CGRP and monomeric human CT, respectively, and expressed in ng and μ g equivalents (eq). The content of immunoreactive CGRP of the neocortex ( n = 3), the cerebellar cortex ( n = 6), the periventricular mesencephalic region ( n = 3) and the thyroid ( n = 5) was similar (mean ± SE, 0.79 ± 0.16 ng eq/g wet tissue 1.51± 0.14 ng eq/g 1.84 ± 0.12 ng eq/g and 5.0 ± 0.9 ng eq/g, respectively), whereas pituitary glands ( n = 21) and medullary thyroid carcinomas ( n = 6) contained higher levels (31.3 ± 5.1 ng eq/g and 7.66 ± 5.42 μg eq/g, respectively). Immunoreactive CT was lowest in the neocortex, cerebellar cortex and the periventricular mesencephalon (0.31 ± 0.07 ng eq/g 0.30 ± 0.09 ng eq/g and 0.26 ± 0.09 ng eq/g, respectively), followed by the pituitary and thyroid (2.77 ± 0.62 ng eq/g and 146 ± 26 ng eq/g, respectively), and was highest in medullary thyroid carcinoma tissue (680 ± 372 μg eq/g). The identification of CGRP-like peptides in the thyroid, pituitary and brain suggests that the production of CGRP may not be organ-specific in man.