27S THYROID IODOPROTEIN. ISOLATION AND PROPERTIES.

thyroglobulin prepared by salting-out methods, of an ultracentrifugal component sedimenting faster than thyroglobulin (i.e. more than 198) has been known for some years (1, 2). Even though not proven, it has been suggested that this component is an iodoprotein (3). It was postulated to be “an aggregated or otherwise altered form of thyroglobulin itself” (4) or an artifact produced during the preparation of thyroglobulin (5). According to Ui and Tarutani (6), however, the so-called F (fast) component is not an artifact and might play a physiologically important role in the thyroid gland. Actually, the nature and significance of the faster sedimenting thyroidal component was unknown, since all prior attempts to isolate this protein had been unsuccessful (3). The purification of the faster sedimenting thyroidal protein has now been achieved by means of two techniques recently used (7) for the preparation of highly purified thyroglobulin: filtration through granulated agar gel and ultracentrifugation in a linear density gradient. Both techniques were designed to isolate thyroid proteins with discrete size and shape characteristics. The purification as well as some molecular and chemical properties of this newly isolated protein are reported in this paper

DUOX Defects and Their Roles in Congenital Hypothyroidism.

Extracellular hydrogen peroxide is required for thyroperoxidase-mediated thyroid hormone synthesis in the follicular lumen of the thyroid gland. Among the NADPH oxidases, dual oxidases, DUOX1 and DUOX2, constitute a distinct subfamily initially identified as thyroid oxidases, based on their level of expression in the thyroid. Despite their high sequence similarity, the two isoforms present distinct regulations, tissue expression, and catalytic functions. Inactivating mutations in many of the genes involved in thyroid hormone synthesis cause thyroid dyshormonogenesis associated with iodide organification defect. This chapter provides an overview of the genetic alterations in DUOX2 and its maturation factor, DUOXA2, causing inherited severe hypothyroidism that clearly demonstrate the physiological implication of this oxidase in thyroid hormonogenesis. Mutations in the DUOX2 gene have been described in permanent but also in transient forms of congenital hypothyroidism. Moreover, accumulating evidence demonstrates that the high phenotypic variability associated with altered DUOX2 function is not directly related to the number of inactivated DUOX2 alleles, suggesting the existence of other pathophysiological factors. The presence of two DUOX isoforms and their corresponding maturation factors in the same organ could certainly constitute an efficient redundant mechanism to maintain sufficient H2O2 supply for iodide organification. Many of the reported DUOX2 missense variants have not been functionally characterized, their clinical impact in the observed phenotype remaining unresolved, especially in mild transient congenital hypothyroidism. DUOX2 function should be carefully evaluated using an in vitro assay wherein (1) DUOXA2 is co-expressed, (2) H2O2 production is activated, (3) and DUOX2 membrane expression is precisely analyzed.info:eu-repo/semantics/publishe