Difference in Glycosylation between Secreted and Pituitary Free α-Subunit of the Glycoprotein Hormones*

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Abstract
The sera of 12 patients with elevated serum concentrations of .alpha.-subunit (.alpha.) were fractionated by gel chromatography on Sephadex G-100. The partition coefficients (Kav) of serum .alpha., measured by radioimmunoassay in each fraction collected, were compared to the Kav of cochromatographed iodinated pituitary human TSH[thyrotropin].alpha.. Six patients had nonneoplastic disorders (2 post-menopausal women, 1 hypothyroid patient, 2 patients with chronic renal failure, and one with TSH-mediated hyperthyroidism). Six patients had neoplastic disorders (3 with TSH-secreting pituitary tumors and 3 with malignant carcinoid tumors). The mean Kav of serum .alpha. from the 12 patients was 0.39 .+-. 0.04, compared to 0.45 .+-. 0.04 for cochromatographed iodinated pituitary TSH.alpha. (P < 0.001). There was no difference in Kav between neoplastic and nonneoplastic serum .alpha.. Gel chromatography of 18 normal human pituitary extracts revealed no significant difference in Kav values between immunoactive intrapituitary .alpha. and cochromatographed iodinated pituitary TSH.alpha.. In contrast to the increased apparent size of serum .alpha., immunoactive serum and intrapituitary TSH.beta. had similar apparent sizes, as determined by gel chromatography. To determine whether the larger MW of serum .alpha. was due to increased terminal glycosylation, serum samples from 3 of the patients were treated with neuraminidase, .alpha. in neuraminidase-treated serum from 2 of the patients coeluted with iodinated pituitary TSH.alpha.. After further treatment of the 3rd patient''s serum with .beta.-galactosidase, serum .alpha. eluted similarly to iodinated pituitary TSH.alpha.. Similar treatment of intrapituitary .alpha. with these glycosidases resulted in minimal change in the Kav. Terminal glycosylation of free .alpha. subunit with galactose and particularly sialic acid appears to be temporally associated with its secretion and accounts for the larger apparent MW of serum, as compared to intrapituitary, .alpha. subunit.
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