Interferon-alpha-2a is a potent inhibitor of hormone secretion by cultured human pituitary adenomas.
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.
Hofland
L J
LJ
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands. hofland@inw3.azr.nl
de Herder
W W
WW
Waaijers
M
M
Zuijderwijk
J
J
Uitterlinden
P
P
van Koetsveld
P M
PM
Lamberts
S W
SW
D000236:Adenoma / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D015408:Gastrinoma / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology*; D015282:Octreotide / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism*; D011994:Recombinant Proteins; D013004:Somatostatin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured
D018491:Dopamine Agonists; D005755:Gastrins; D007328:Insulin; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D001971:Bromocriptine; D013004:Somatostatin; D011388:Prolactin; D015282:Octreotide