title: Unique binding pattern to concanavalin A lectin of glycoprotein hormones alpha-subunit hypersecreted by non-functioning pituitary adenomas.
abstract: This study analyzed the structural differences of the carbohydrate chains of circulating free alpha-submit (alpha-SU) hypersecreted in various 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 of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free alpha-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 alpha-SU in serum and in Con-A fractions were measured by a sensitive and specific IRMA. Free alpha-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 alpha-SU from patients with TSH- and GH-secreting adenomas showed a binding pattern to Con-A 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 alpha-SU molecules eluted in the FB fraction, was found in patients with pure alpha-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 alpha-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 affinity chromatography clearly demonstrate that carbohydrate branching of circulating free alpha-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 alpha-SU forms that firmly bind to Con-A in patients with pure alpha-secreting adenomas, seems to be pathognomonic of non-functioning pituitary adenomas.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Asteria
authors.forename: L
authors.initials: L
authors.lastname: Persani
authors.forename: M
authors.initials: M
authors.lastname: Ferrari
authors.forename: P
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D000236:Adenoma / Q000097:blood*; D000328:Adult; D002276:Carcinoid Tumor / Q000097:blood; D002846:Chromatography, Affinity; D003208:Concanavalin A; D005333:Fetus; D006001:Glycoconjugates / Q000737:chemistry; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood; D007414:Intestinal Neoplasms / Q000097:blood; D010911:Pituitary Neoplasms / Q000097:blood*; D017698:Postmenopause; D011485:Protein Binding; D014511:Uremia / Q000097:blood
chemical_list: D006001:Glycoconjugates; D015292:Glycoprotein Hormones, alpha Subunit; D003208:Concanavalin A