ON THE RELATIONSHIP BETWEEN COMPLETION OF N-ACETYLLACTOSAMINE OLIGOSACCHARIDE UNITS AND IODINE CONTENT OF THYROGLOBULIN - A REINVESTIGATION

Lack of completion of N-acetyllactosamine-type glycosylation on thyrog lobulin (Tg) has been implicitly considered as an etiological factor o f some thyroid disorders, i.e. goiter and hypothyroidism. However, the re is some evidence that Tg with incompletely processed N-acetyllactos amine glycans occurs in the normal gland. Recent findings demonstrated that exposed N-acetylglucosamine (GlcNAc) residues present on interna lized glycoprotein in the thyrocyte may act as a retention signal that prevents lysosomal homing and triggers recycling of GlcNAc-bearing mo lecules through galactosyltransferase- and thyroperoxidase-containing compartments of the Golgi apparatus. This finding raises the possibili ties 1) that exposed GlcNAc residues are not randomly distributed, but are mainly present on immature Tg; and 2) that this process promotes elongation of complex glycans, thereby eliminating the retention signa l. To further validate this hypothesis, we reinvestigated the relation ship between the iodine content and the glycan completion of porcine T g of luminal origin. Tg subpopulations were separated according to the ir iodine content on rubidium chloride centrifugation gradients, and t heir interactions with various plant and animal lectins were analyzed in solid phase assays. Iodine content used as an index of age ranged f rom 0.6-1.2%. There was no significant correlation between iodine cont ent and either neutral sugar or oligomannosidic oligosaccharide conten t, as judged by chemical methods or interaction with [I-125]Solanum tu berosum and [I-125]Pisum sativum agglutinins. In contrast, the number of GlcNAc-accessible residues (as judged by interaction with [I-125]Ba ndeiraea simplificolia II) decreased as iodine content increased. Thes e changes were concomitant with an increase in galactose (measured by interaction with [I-125]R-icinus communis and [I-125]galactosidase (Ga l)/GalNAc rat hepatic lectin) and sialic acid content. Related experim ents using a Tg subpopulation depleted in GlcNAc-exposed residues by p assage through a B. simplificolia II affinity column showed that the c apacity of this subpopulation to bind to membranes was lowered compare d to that of the total Tg. These results support the following conclus ions: 1) in normal glands, all or part of the Tg molecules are secrete d in an incompletely glycosylated form; and 2) iodine organification i s correlated with glycan completion. Therefore, asialoagalactothyroglo bulin appears to be a physiological precursor for an efficient recycli ng mediated by the GlcNAc receptor to the iodination site. New insight s in thyroid disorders are discussed.