Acute stimulation of chromaffin cell proliferation in the adult rat adrenal medulla.

Susceptible strains of rats develop adrenal medullary hyperplasia and neoplasia after long-term administration of the antihypertensive drug reserpine, or of other pharmacologic agents which alter neuroendocrine function. These proliferative lesions are of potential medical importance as a model for familial multiple endocrine neoplasia syndromes, and are of fundamental interest because they might elucidate mechanisms regulating chromaffin cell proliferation during normal development. To study the initiation of the adrenal lesions, chromaffin cell mitoses were counted in adult male rats injected with reserpine or control solvent for 5 days, with the final injection containing colcemid to arrest cells in mitosis. Rare mitoses were observed in mature-appearing epinephrine and norepinephrine cells in control adrenals. Reserpine caused an 8-fold increase in chromaffin cell mitoses in otherwise histologically normal glands, and the mitotic cells after reserpine administration showed marked granule depletion. Reserpine directly depletes catecholamine stores and reflexively increases neurogenic stimulation of chromaffin cells to increase catecholamine synthesis. The findings suggest that signals regulating function also regulate proliferation of mature chromaffin cells, and that prolongation of these signals or superimposed abnormalities may lead to pathologic proliferative states. The reserpine model may be a useful system for elucidating normal and pathologic mechanisms of signal transduction.