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Interferon-alpha-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas
L J Hofland1, W W de Herder, M Waaijers
1Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands. hofland@inw3.azr.nl
Abstract:
Interferon-alpha (IFN alpha) may exert direct inhibitory effects on cell proliferation and on the production of different peptide hormones. We investigated the effect of IFN alpha 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 alpha (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 alpha, 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 alpha resulted in inhibition of the secretion of gonadotropins and/or alpha-subunit in all cases (27-62%), whereas in the prolactinoma cultures PRL secretion was inhibited by IFN alpha in all cases (37-76%). The effect of IFN alpha 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 alpha was accompanied by inhibition of the intracellular hormone concentrations. The effect of IFN alpha 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 alpha for various malignancies. In conclusion, the potent antihormonal effect of IFN alpha 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 alpha 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.
Insights
Interferon-alpha (IFN alpha) effectively inhibited hormone secretion in various pituitary adenoma cell cultures. This suggests IFN alpha may be a potential treatment for specific, resistant pituitary tumors.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Interferon-alpha (IFN alpha) is known to inhibit cell proliferation and peptide hormone production.
- Pituitary adenomas are tumors of the pituitary gland that can overproduce hormones.
Purpose of the Study:
- To investigate the in vitro effects of IFN alpha on hormone secretion from different types of pituitary adenomas.
- To determine the potential of IFN alpha as a therapeutic agent for pituitary adenomas.
Main Methods:
- Primary cell cultures of human pituitary adenomas (GH-secreting, nonfunctioning/gonadotroph, and prolactinomas) were treated with IFN alpha.
- Hormone secretion (GH, PRL, gonadotropins, alpha-subunit) and intracellular hormone levels were measured.
- Dose-dependency and additive effects with bromocriptine and octreotide were assessed.
Main Results:
- IFN alpha significantly inhibited GH and/or PRL secretion in GH-secreting adenomas, with prolonged incubation showing marked inhibition.
- All nonfunctioning/gonadotroph adenoma cultures showed inhibition of gonadotropin and/or alpha-subunit secretion.
- Prolactinoma cultures exhibited significant inhibition of PRL secretion by IFN alpha.
- The inhibitory effect was dose-dependent with a low IC50 (2.3 U/mL) and additive to dopamine agonists and somatostatin analogs.
Conclusions:
- IFN alpha demonstrates potent in vitro antihormonal effects on cultured pituitary adenomas.
- IFN alpha may offer therapeutic benefits for selected patients with secreting pituitary adenomas, particularly those resistant to other treatments.
- Given adverse reactions, IFN alpha should be considered for inoperable, aggressive, and treatment-resistant pituitary macroadenomas.