This occurs, for example, in the synthesis of the Nylon family of polymers in which the eliminated H2O molecule comes from the hydroxyl group of the acid and one of the amino hydrogens: Note that the monomeric units that make up the polymer are not identical with the starting components. or polymerization involves the rearrangement of bonds within the monomer in such a way that the monomers link up directly with each other: In order to make this happen, a chemically active molecule
(called an ) is needed to start what is known as a .
In rat thyroid FRTL-5 cells, Tg (at physiologic concentrations) suppresses the mRNA expression levels of several genes involved in TH synthesis, including Tg, Tpo, and Slc5a5 (NIS) (). Tg is proposed to regulate cell growth and gene transcription by mimicking transforming growth factor (TGF)-β in certain cell types (;). Tg binds several proteins on the surface of thyroid cells (e.g., asialoglycoprotein receptor (ASGPR; ()), megalin (gp300; ()), and an N-acetylglucosamine receptor ()), but none are significantly associated with intracellular signaling. These Tg-binding proteins are not specific to Tg, and are able to bind other large glycoproteins.
Tg synthesis is restricted to the thyroid gland. Tg is secreted and stored in the colloid inside of the thyroid follicles. Newly secreted Tg remains near the apical membrane of thyroid cells, where it undergoes hormone formation and is internalized and/or degraded rapidly. Tg in the center of the follicle is stored in the form of aggregates to function as an iodine and hormone reservoir.
Within the thyroid gland, epithelial cells synthesize thyroid hormones and are arranged as thyroid follicles. Between the thyroid follicles are parafollicular (alternatively, C cells), which secrete the hormone calcitonin. Tg is secreted by the thyroid cell into the follicular lumen by regulated (nonconstitutive), merocrine secretion (;). Upon stimulation by thyroid-stimulating hormone (TSH), Tg is reabsorbed by endocytosis/pinocytosis or phagocytosis (rodents only) to form endocytic/pinocytic vesicles or phagosomes, respectively (;). Thyroid hormone synthesis is regulated by the hypothalamic-pituitary-thyroid axis (HPT) negative feedback system, which involves interactions between the thyroid gland and circulating hormones. In the HPT, thyroid hormone synthesis is induced by TSH, which is secreted from anterior pituitary endocrine cells called thyrotropes. Increased thyroid hormone levels suppress further TSH secretion by acting on the hypothalamus, subsequently inhibiting the release of TSH-releasing hormone (TRH). TSH binding to the TSHR at the basal membrane of the thyroid follicle stimulates Tg expression via an increase in the intracellular level of cyclic adenosine monophosphate (cAMP) as well as the stimulation of thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS) (). After synthesis, Tg is transported to the apical membrane whereby it is released into the follicular lumen. At the apical membrane TPO and H2O2 catalyze the iodination of tyrosine residues on Tg to produce mono- (MIT) and di-iodotyrosines (DIT). Subsequent coupling of MIT and DIT catalyzes the production of T3 and T4. The iodinated Tg is pinocytosed through the apical membrane and into lysosomes where it undergoes proteolysis to release T3 and T4 through the basal membrane into the blood for action at peripheral target tissues whereby they control metabolism ().
