Unique binding pattern to Concanavalin A lectin of glycoprotein hormones α-subunit hypersecreted by non-functioning pituitary adenomas

This study analyses the structural differences of the carbohydrate chains of circulating free α-subunit (α-SU) hypersecreted in various non- tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH-, GH- and pure α- secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free α-SU were investigated by means of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free α-SU in three different fractions (unbound = UB, weakly bound = WB and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of α-SU in serum and in Coma fractions were measured by a sensitive and specific IRMA. Free α-SU hypersecreted from postmenopausal women, primary hypothyroids, and patients with chronic uremia showed similar binding patterns to Con-A, the percentage of UB fractions (UB: 44.5 ± 1.9%, 39.5 ± 3.8%, 48.2 ± 5.6% respectively) being higher than both WB and FB fractions (WB: 33.2 ± 1.4%, 30.7 ± 4.6%, 28.5 ± 2.1%; FB: 22.3 ± 0.7%, 29.8 ± 6.6%, 23.3 ± 4.2% respectively). In normal fetuses the amount of UB fraction was very high (UB:70.7 ± 5.4%). Free α-SU from patients with TSH- and GH-secreting adenomas showed a bInding pattern to Coma significantly different from that observed in postmenopausal women taken as controls, the WB fractions being significantly higher (WB: 56.9 ± 16.8% and 71 ± 12.4% respectively, P <0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature α-SU molecules eluted in the FB fractions, was found in patients with pure α-secreting adenomas. This chromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoids (FB: 41.8 ± 5.0%, 22.3 ± 0.7%, 16.8 ± 6.6%, 10.6 ± 2.0% respectively). Moreover, in these latter patients the pattern of free α-SU binding was exactly the opposite of that observed in pure α-secreting adenomas, with a prevalence of mature α-SU molecules (UB:59.1 ± 4.4 vs 18.3 ± 7.2%). In conclusion, our data on Con-A affinity chromatography clearly demonstrate that carbohydrate branching of circulating free α-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral conditions. Moreover, the finding of a greater proportion of circulating free α-SU forms that firmly bind to Con-A in patients with pure α-secreting adenomas, seems to be pathognomonic of non-functioning pituitary adenomas.