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EXCESS FREE ALPHA RELATIVE TO BETA SUBUNITS OF THE GLYCOPROTEIN HORMONES IN NORMAL AND ABNORMAL HUMAN PITUITARY GLANDS

Extracts of thirteen normal pituitaries from five men, three premenopausal women, and five postmenopausal women were fractionated by Sephadex G‐100 chromatography; alpha subunit, TSH‐β, LH‐β, and FSH‐β, as well as complete TSH, LH, and FSH, were measured by radioimmunoassay (RIA) in each fraction collected. In spite of variability in subunit content among normal pituitaries, a consistent excess of free alpha subunits relative to the sum of all free pituitary beta subunits was demonstrated in each normal pituitary (P < 0·025); the alpha to beta subunit ratio ranged from 1·29–8·31. In addition, in normal pituitary extracts the ratio of free alpha to alpha combined with beta subunits in the complete glycoprotein hormones generally exceeded 1 (mean 1·57), although the free alpha to combined alpha excess was not statistically significant. In extracts of pituitaries from two hypothyroid and four hyperthyroid patients, the excess of alpha to all pituitary beta subunits persisted. Centrifugation of pituitary extracts at 35 000g, rather than 1500g, prior to gel chromatography decreased the small percentage of void volume immunoactivity in both complete glycoprotein hormone and subunit RIAs, suggesting that it may have been caused by adsorption to membrane components in the extracts. Different methods of preparing the pituitary homogenates did not change the amount or ratio of alpha to beta subunits extracted. Heterogeneity was observed in pituitary alpha and TSH‐β by gel chromatography, suggesting that differences in the amount of glycosylation existed among intrapituitary free alpha and TSH‐β subunits. These studies, as well as prior studies of de novo subunit biosynthesis and in vivo secretory rates, support the concept that the excess content of free alpha to all free beta subunits in the pituitary reflects greater synthesis of alpha subunits; beta subunit synthesis appears to be the limiting factor in the production of complete TSH, LH, and FSH.