Histopathological and physiological characteristics of cultured human ACTH-secreting cells derived from a rapidly growing pituitary adenoma.

We observed the histopathological and physiological characteristics of adrenocorticotropic hormone (ACTH)-secreting adenoma cells derived from a rapidly growing pituitary adenoma, which have firm cell attachment and well-preserved hormonal function in a relatively longterm culture. Corticotrophs, obtained from a 43-year-old woman with Cushing's disease in whom plasma ACTH levels increased in response to 1-deamino-8-D-arginine vasopressin (DDAVP) stimulation and the proliferative potential was very high, were grown in tissue culture for up to 6 months. The morphological features were observed by phase contrast and electron microscopy. The cultured cells were incubated with corticotroph-releasing hormone (CRH), arginine vasopressin (AVP), or DDAVP, and ACTH in the medium was measured by radioimmunoassay (RIA). The morphology of the ACTH-secreting adenoma cells in culture revealed a mixed population of formed clusters and spindle-shaped fibroblast-like cells. The adenoma cells were immunohistochemically positive only for ACTH. On electron microscopic observation, pituitary tumor cells obtained 6 days after seeding demonstrated many secretory granules, well-developed rough endoplasmic reticulum, and mitochondria; fewer secretory granules were observed after cultivation for 24 days. ACTH levels in the incubation media were elevated with stimulation by DDAVP, AVP, or CRH. In this study, the establishment of relatively longterm culture of human pituitary adenoma cells seemed to be due to the high proliferative potential of this adenoma. This in vitro study may imply that DDAVP as well as AVP directly stimulates ACTH release from corticotropic adenoma cells.