Interferon-α-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas

Abstract

Interferon-α (IFNα) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFNα on hormone production by 15 GH-secreting pituitary adenomas, 4 clinically nonfunctioning or gonadotroph pituitary adenomas, and 4 prolactinomas in vitro. In the GH-secreting pituitary adenoma cultures, a short term (72-h) incubation with IFNα (50-100 U/mL) significantly inhibited GH secretion in 3 of 7 cases and PRL secretion in 6 of 7 cultures. During prolonged incubation (14 days) with IFNα, 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 IFNα resulted in inhibition of the secretion of gonadotropins and/or α-subunit in all cases (27-62%), whereas in the prolactinoma cultures PRL secretion was inhibited by IFNα in all cases (37-76%). The effect of IFNα was additive to the inhibitory effects of the dopamine agonist bromocriptine (10 nmol/L) or the somatostatin analog octreotide (10 nmol/L). The inhibition of hormone secretion by IFNα was accompanied by inhibition of the intracellular hormone concentrations. The effect of IFNα was dose dependent, with an IC50 for inhibition of hormone secretion of 2.3 ± 0.3 U/mL (n = 5), which is relatively low compared with the concentrations that are reached in patients treated with IFNα for various malignancies. In conclusion, the potent antihormonal effect of IFNα on cultured pituitary adenomas suggests that this drug might be of benefit in the treatment of selected patients with secreting pituitary adenomas. As treatment with IFNα is associated with considerable adverse reactions, studies with this drug should only be considered in inoperable, invasive aggressive, and dopamine agonist- and/or somatostatin analog-resistant functioning pituitary macroadenomas.