Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas

Interleukins and their receptors are expressed intrinsically in the anterio r pituitary and regulate hormone production and cell proliferation. It has previously been shown that interleukin-6 (IL-6) regulates hormone secretion in normal pituitary cells and cell lints. Here we examined the effects of IL-6 on propiomelanocortin (POMC) expression and ACTH production in cortico troph adenoma cells in vitro. We found that IL-6 stimulates both ACTH secre tion and POMC gene expression in corticotroph adenoma cell cultures. This f irst demonstration of the stimulatory action of IL-6 on human corticotroph adenoma cell function provides further evidence for a direct action of IL-6 on corticotroph pituitary cells. We have confirmed previous reports of IL- 6 production by corticotroph adenoma cells and in addition. demonstrated fo r the first time that the synthetic glucocorticoid dexamethasone is a poten t suppressor of intratumoral IL-6 production. This intratumoral produced IL -6 may be in part responsible, in an autocrine manner, for the stimulation of ACTH synthesis and secretion. Our results suggest that IL-6 might play a role in the pathogenesis of Gushing's disease. However, elevated glucocort icoid levels in patients with Gushing's disease may prevent excessive actio n of IL-6 on ACTH production and tumor progression of corticotroph adenomas in vivo.