Interferon-␣ (IFN␣) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFN␣ on hormone production by 15 GHsecreting pituitary adenomas, 4 clinically nonfunctioning or gonadotroph pituitary adenomas, and 4 prolactinomas in vitro. In the GHsecreting pituitary adenoma cultures, a short term (72-h) incubation with IFN␣ (50 -100 U/mL) significantly inhibited GH secretion in 3 of 7 cases and PRL secretion in 6

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... 7 cultures. During prolonged incubation (14 days) with IFN␣, GH and/or PRL secretion was significantly inhibited in 7 of 8 cultures (GH, 17-78% inhibition; PRL, 39 -88% inhibition). In the clinically nonfunctioning or gonadotroph cultures, incubation with IFN␣ resulted in inhibition of the secretion of gonadotropins and/or ␣-subunit in all cases (27-62%), whereas in the prolactinoma cultures PRL secretion was inhibited by IFN␣ in all cases (37-76%). The effect of IFN␣ was additive to the inhibitory