%0 Journal Article
%T The Emerging Roles of Thyroglobulin
%A Yuqian Luo
%A Yuko Ishido
%A Naoki Hiroi
%A Norihisa Ishii
%A Koichi Suzuki
%J Advances in Endocrinology
%D 2014
%R 10.1155/2014/189194
%X Thyroglobulin (Tg), the most important and abundant protein in thyroid follicles, is well known for its essential role in thyroid hormone synthesis. In addition to its conventional role as the precursor of thyroid hormones, we have uncovered a novel function of Tg as an endogenous regulator of follicular function over the past decade. The newly discovered negative feedback effect of Tg on follicular function observed in the rat and human thyroid provides an alternative explanation for the observation of follicle heterogeneity. Given the essential role of the regulatory effects of Tg, we consider that dysregulation of normal Tg function is associated with multiple human thyroid diseases including autoimmune thyroid disease and thyroid cancer. Additionally, extrathyroid Tg may serve a regulatory function in other organs. Further exploration of Tg action, especially at the molecular level, is needed to obtain a better understanding of both the physiological and pathological roles of Tg. 1. Introduction The thyroid gland is comprised of thyroid follicles, in which thyrocytes surround a follicular lumen with the apical surface of a thyrocyte facing the lumen while the basal surface faces a basket-like capillary network evenly surrounding each thyroid follicle. Thyroglobulin (Tg), which is well known as the macromolecular precursor of thyroid hormone, is the most important and abundant protein produced and stored in thyroid follicles [1]. In the last decade, in addition to its well-established role as the precursor of thyroid hormone, we have revealed important novel roles for Tg. We found that Tg can serve as a negative regulator of thyroid function-related genes and an inducer of thyrocyte growth. In this review, we will summarize these studies of newly recognized Tg action and discuss the potential involvement of Tg in the development of thyroid disorders. Despite enormous advances in understanding the structure and the role of Tg in hormonogenesis, our understanding of the molecular function of Tg remains incomplete. Therefore, we will also include discussion of unanswered questions regarding Tg in this review that we hope will inspire further studies. 2. The Synthesis of Tg and Secretion of Thyroid Hormones Tg is synthesized as a 12S molecule (330£¿kDa) and in its most stable state forms a 19S dimer (660£¿kDa). Biosynthesis of thyroid hormones and their release in the circulation include the following sequence of events [1, 2]. Iodide from the blood stream is concentrated by the sodium iodide symporter (NIS) [3] at the basolateral surface of a thyrocyte
%U http://www.hindawi.com/journals/aen/2014/189194/