Highlights of the 78th Annual Meeting American Thyroid ... - Thyrolink

American Thyroid Association – Highlights of the 78 th Annual Meeting11Translational SymposiumThyroid Hormone Synthesisand ThyronaminesThe enzyme dehalogenase was cloned and four patientswith defects in the gene have been identified by JoseMoreno, Rotterdam, NL. Dehalogenase requires NADPHto recapture iodine from the monoiodotyrosine anddiiodotyrosine produced in the thyroid when iodinatedthyroglobulin is being degraded. All four of the patientsstudied had goiters, and the mutations identified alloccurred near the NADPH binding pocket in the enzyme.Two of these individuals had been screened as neonatesand, at that time, the test indicated that theywere euthyroid. One of them developed a large goiterat 18 months and became mentally retarded. The otherpatient developed large goiter at 8 years but was mentallynormal.Dual oxidase 2 (DUOX2) is one of two NADPH oxidasesexpressed on the apical membrane of the thyrocyte,which generate the H 2 O 2 needed to iodinate thyroglobulin.Attempts to transfect cells with the DUOX genesto express functional enzyme had been unsuccessfuluntil Helmut Grasberger, Chicago, IL, found the phylogeneticallyhighly conserved DUOX2A gene locatedhead-to-head with the DUOX2 gene on chromosome15. DUOX2A encodes a protein that resides in the endoplasmicreticulum, where it functions as a maturationfactor that is needed in order for DUOX2 to be expressedon the plasma membrane. In this meeting, Grasbergerreported finding a mutant DUOX2A gene in a goitrouspatient who has a positive perchlorate discharge test,whereas the DUOX genes were normal.A new thyroid hormone that has unusual activities inhibernating animals has been described. By improvinghis assay of 3-iodothyronamine (T1-AM), Tom Scanlon,Portland, OR, demonstrated that T1-AM is an endogenousmetabolite of thyroid hormone. It is found predominantlyin the thyroid, but lower levels are foundin fat. T1-AM in the blood is 99 % bound to alpha-2macroglobulin. Furthermore, T1-AM is a ligand forTAAR1, which was previously considered an orphannuclear receptor; however, T1-AM also appears to bindto alpha-2 adrenergic receptors. This substance has dramaticeffects on body temperature and blood glucoselevel when administered to hibernating rodents.Stem Cells and Thyroid DevelopmentReigh-Yi Lin, New York, NY, briefly reviewed stemcell biology and his 2003 report, which showed thatincubating mouse embryonic stem cells with TSH canresult in embryoid bodies that express PAX8, NIS, thyroperoxidaseand TSH receptor (in normal development,however, the thyroid anlage appears well beforethe appearance of TSH or its receptor.) A 2007 paperby Mitsutaki et al. used cell sorting to detect a sidepopulationin some thyroid cell lines, and was mostabundant in the ARO anaplastic carcinoma cell line.Cells from this side-population formed more clonesthan those from the main population. The abundanceof this side-population increased when ARO cells weregrown at low density, but cells from both populationscan form tumors in nude mice.Michel Polak and colleagues, Paris, France, reviewedhow gene expression changes during human thyroidorganogenesis. PAX8 is strongly expressed both in theultimobranchial body and in the thyroid anlage in thefloor of the midgut, and it persisted as follicular cellsdeveloped. TTF1 was expressed weakly and FOXE1was even weaker in the thyroid primordium, but bothremained expressed as the fetal gland developed. TPO,pendrin, and thyroglobulin expression increased as colloidfollicles appeared, while NIS expression increaseddramatically, first located around the nuclei but thenin the basolateral membrane. In contrast, the levels ofTSHR, PAX8, TTF1, and FOXE1 showed no changesover this time.Liuska Pesce and Peter Kopp, Chicago, Il, reportedthat TSH does not increase pendrin mRNA levels inthe thyroid: Pendred syndrome appears to reflect aproblem in transporting the iodide/chloride transporterpendrin from the endoplasmic reticulum to the plasma