Effects of long term treatment with corticotropin releasing factor on corticotropic tumor cells in vitro.

hCRF inhibits proliferation of corticotropic tumor cells cultivated in serum-reduced medium via interaction with CRF-receptors. This effect was attenuated by the specific antagonist hCRF (9-41), but not by a variety of substances which are inhibitors of cAMP production or cAMP-dependent kinases, suggesting that the effect was not mediated via cAMP. The growth inhibiting effect of hCRH was developed after 4 h incubation, a longer hCRF treatment did not change the effect observed after 4 h. Simultaneously, after hCRF treatment for 4 days the cells were insensitive for ACTH release by hCRF stimulation despite of an increase in the number of secretory granules. The results show that the inhibition of proliferation of pituitary tumor cells by hCRF seems to be a rapid receptor-mediated process connected with morphological changes, but not mediated via activation of adenylate cyclase.