COMPARATIVE-STUDY BETWEEN NORMAL RAT CHROMAFFIN AND PC12 RAT PHEOCHROMOCYTOMA CELLS - PRODUCTION AND EFFECTS OF CORTICOTROPIN-RELEASING HORMONE

The adrenal medulla of several species and some human pheochromocytoma s contain CRH. The first aim of the present work was to find out wheth er normal rat adrenal chromaffin cells and the PC12 rat pheochromocyto ma cell line produce CRH in vitro and what regulates its production. C RH was measured and characterized in the media of both types of chroma ffin cells under basal conditions and after exposure to K+, nicotine, interleukin-1 beta, and nerve growth factor (NGF). The second aim was to examine the biological effect of exogenous CRH (and of its antagoni st) on the production of catecholamines from these two types of cells. Our results are as follows: 1) Both types of chromaffin cells contain ed and secreted comparable amounts of immunoreactive-CRH under basal c onditions and after K+-induced depolarization, nicotine, and interleuk in-1 beta; 2) the physicochemical characteristics of the immunoreactiv e-CRH in the cells and the media were identical to the putative CRH pe ptide on both sieve chromatography and RP-HPLC; 3) synthetic CRH induc ed the production of catecholamines from both cell types in a dose- an d time-dependent manner; this effect was abolished by the antagonist, ct helical CRH; 4) exposure of PC12 cells to NGF (for 1 week) resulted in their neuronal differentiation and the stimulation of their produc tion of CRH by 30 times and of dopamine by 10 times, compared with par allel controls; this effect of NGF was abolished by alpha helical CRH. In conclusion, our data suggest that the production of CRH by PC12 ce lls represents the preservation of a normal chromaffin cell characteri stic rather than a tumor-induced ectopic phenomenon.