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Interferon--2a Is a Potent Inhibitor of Hormone Secretion by Cultured Human Pituitary Adenomas

Department of Internal Medicine III, Erasmus University, 3015 GD Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: L. J. Hofland, Ph.D., Department of Internal Medicine III, University Hospital Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: hofland{at}inw3.azr.nl

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 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 IFN (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 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 effects of the dopamine agonist bromocriptine (10 nmol/L) or the somatostatin analog octreotide (10 nmol/L). The inhibition of hormone secretion by IFN was accompanied by inhibition of the intracellular hormone concentrations. The effect of IFN 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 IFN for various malignancies. In conclusion, the potent antihormonal effect of IFN 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 IFN 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.

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