Involvement of interleukin-1 and interleukin-1 receptor antagonist in rat pituitary cell growth regulation

Interleukin-1 (IL-1), one of the mediators of the interaction between the immune and the neuroendocrine system, is well known to modulate anterior pituitary hormone secretion. As IL-1 influences growth of various cell types, we investigated whether IL-1 is also a growth factor of pituitary cells. We demonstrate that IL-1 dose and time dependently inhibits the growth of normal rat pituitary cells under serum-free conditions. The inhibitory potencies of IL-1 alpha (ED50, 8 pg/ml) and IL-1 beta (ED50, 6 pg/ml) were nearly identical. In the presence of low amounts of serum, both IL-1 alpha (ED50, 130 pg/ml) and IL-1 beta (ED50, 90 pg/ml) were less effective in inhibiting growth. The IL-1-induced growth inhibition was IL-1 receptor mediated, because both IL-1 alpha- and IL-1 beta-mediated growth suppression could be completely reversed by the IL-1 receptor antagonist, the physiological counterpart of IL-1. In the mammosomatotroph GH3 rat pituitary tumor cell line, IL-1 failed to influence growth, indicating that either IL-1 receptors are missing or the IL-1 signaling pathway is uncoupled from the growth regulation. In contrast to growth, in our rat pituitary monolayer cell culture system, IL-1 did not affect ACTH, GH, or PRL secretion as described previously. This discrepancy suggests the involvement of different mechanisms in the IL-1-induced mediation of growth and hormone secretion.