Secretion of Glycoprotein Hormoneα-Subunit by Pituitary Tumors*

Abstract

Serum glycoprotein hormone alpha-subunit levels were determined in 165 patients with pituitary adenomas. Elevated serum alpha-subunit levels were found in 17 patients (acromegaly, 5 of 58; prolactinoma, 6 of 56; nonfunctioning adenoma, 5 of 32; and ACTH-producing adenoma, 1 of 19), most of whom had normal serum TSH and gonadotropin levels. When TRH (0.5 mg) was injected iv in the 6 prolactinoma patients with elevated serum alpha-subunit levels, serum PRL and alpha-subunit levels increased in only 1 patient. Four acromegalic patients with high serum alpha-subunit levels received TRH; serum GH and alpha-subunit increased in 1 patient and did not change in 2, and only serum GH increased in the remaining patient. Oral administration of bromocriptine (5 mg), on the other hand, consistently decreased serum alpha-subunit and PRL levels in 2 patients with prolactinoma and alpha-subunit and GH levels in 1 acromegalic patient. When serum from 3 patients was subjected to Sephadex G-100 gel filtration, immunoreactive alpha-subunit eluted in a single peak, which emerged in fractions corresponding to [125I]TSH alpha. Concanavalin A (Con A) affinity chromatography revealed that the major portion of immunoreactive alpha-subunit was retained to Con A. A pituitary adenoma removed at surgery from a patient with acromegaly was studied in monolayer cell culture. Secretion of both alpha-subunit and GH from cultured adenoma cells was stimulated by TRH and suppressed by dopamine in a dose-dependent manner. Immunohistochemistry of the pituitary adenomas removed from patients with prolactinoma and acromegaly who had high serum alpha-subunit levels demonstrated alpha-subunit-containing cells as well as PRL- or GH-containing cells. These results suggest that elaboration of glycoprotein hormone alpha-subunit occurs without concurrent production of glycoprotein hormones in a substantial number of patients with pituitary adenomas and that alpha-subunit responses to stimuli in such adenomas are generally parallel with those of the concomitantly produced hormones.