UNIQUE BINDING PATTERN TO CONCANAVALIN-A LECTIN OF GLYCOPROTEIN HORMONES ALPHA-SUBUNIT HYPERSECRETED BY NONFUNCTIONING PITUITARY-ADENOMAS

This study analyzes the structural differences of the carbohydrate cha ins of circulating free alpha-subunit (alpha-SU) hypersecreted in vari ous non-tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH- , GH-and pure alpha-secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free alpha-SU were investigated by means o f lectin affinity chromatography using Concanavalin A (Con-A), which a llows the separation of free alpha-SU in three different fractions (un bound = UB, weakly bound = WE and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of al pha-SU in serum and in Con-A fractions were measured by a sensitive an d specific IRMA. Free alpha-SU hypersecreted from postmenopausal women , primary hypothyroids, and patients with chronic uremia showed simila r 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 WE and EB fractions (WE: 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). I n normal fetuses the amount of UB fraction was very high (UB: 70.7 +/- 5.4%). Free alpha-SU from patients with TSH-and GH-secreting adenomas showed a binding pattern to Con-A significantly different from that o bserved in postmenopausal women taken as controls, the WE fractions be ing significantly higher (WE: 56.9 +/- 16.8% and 71 +/- 12.4% respecti vely, P < 0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature alpha-SU molecules eluted in the FB fract ions, was found in patients with pure alpha-secreting adenomas, This c hromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoi ds (FB: 41.8 +/- 5.0%, 22.3 +/- 0.7%, 16.8 +/- 6.6%, 10.6 +/- 2.0% res pectively). Moreover, in these latter patients the pattern of free alp ha-SU binding was exactly the opposite of that observed in pure alpha- secreting adenomas, with a prevalence of mature alpha-SU molecules (UB : 59.1 +/- 4.4 vs 18.3 +/- 7.2%). In conclusion, our data on Con-A aff inity chromatography clearly demonstrate that carbohydrate branching o f circulating free alpha-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral co nditions, Moreover, the finding of a greater proportion of circulating free alpha-SU forms that firmly bind to Con-A in patients with pure a lpha-secreting adenomas, seems to be pathognomonic of non-functioning pituitary adenomas.