Thyroid hormones and the control of cell proliferation or cell differentiation: Paradox or duality?

Abstract

Thyroid hormones and the control of cell proliferation or cell differentiation: paradox or duality?. Molecular and Cellular Endocrinology, Elsevier, 2009, 313 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryAmphibian metamorphosis perfectly illustrates a key paradox: thyroid hormones control diverse cellular processes depending on the tissue context. This point is also reinforced by a recent accumulation of evidence. For example, thyroid hormones and their nuclear receptor TRs have been described to function in different systems in synergy and/or in antagonism with other signaling pathways. This interaction helps explain their pleiotropic roles. This review summarizes the most important advances in this field, focusing in particular on the key action of thyroid hormones in controlling the balance between the processes of cell proliferation and cell differentiation in a few organs, with special attention paid to the intestine. We highlight similarities between the cellular and molecular events occurring during postnatal intestinal maturation at metamorphosis in amphibians, and comparable events observed at weaning in mice. 1-Introduction1.1 Thyroid hormone production Thyroid hormones (THs), L-thyroxine or T4 and 3,5,3'-L-triiodothyronine or T3, are essential for the development of several organs, including the central nervous system, skeleton, heart, intestine, skeletal muscle and sensory organs. Moreover, they also have important regulatory effects on oxygen consumption and metabolic rate (Oppenheimer et al., 1987). The follicular cells of the thyroid gland synthesize and secrete both hormones, but T4 is the most abundant. This process is under the control of circulating THs levels through the hypothalamuspituitary-thyroid feedback regulatory loop (rev. in Fredric and Wondisford, 2004). The intracellular concentration of T3 is dependent upon the uptake of T3 and T4, and their subsequent metabolism (Bianco and Kim, 2006). In fact, both hormones are actively transported across the cell membrane by specific transporter proteins, of which monocarboxylate transporter-8 is the best characterized (Dumitrescu et al., 2004;Friesema et al., 2004; rev. in Refetoff andDumitrescu, 2007 andVisser et al., 2007). Three iodothyronine deiodinase selenoenzymes (D1, D2 and D3) regulate TH activation and catabolism (Bianco and Kim, 2006). D1 and D2 catalyze the 5'-deiodination of T4 to its active metabolite T3. T3 is generated from the activity of D1, which is the main source of circulating T3. In contrast, D2 is the isoenzyme primarily responsible for local production of T3 in target cells. T3 derived from ...

Histological and immunohistochemical changes of the thyroid gland during the foetal and postnatal period of development in indigenous Large White crossbred pigs

“…The effects of the thyroid hormones on growth and metabolism in all stages of mammalian development are well documented (Janini et al, 1995;Huszenica et al, 2002;Capen & Martin, 2003). These hormones have important effects on cell proliferation, differentiation, and migration as well as growth and metabolism of embryos (Krees et al, 2009). They are also important in normal reproduction, productive performance such as growth, milk and hair fibre production in domestic animals and hence affect farm animal productivity (Tondini, 2007).…”

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“…In addition, the transport of T4 and T3 in and out of cells is controlled by several classes of transmembrane TH-transporters (THTs) [56], including members of the organic anion transporter family (OATP), L-type amino acid transporters (LATs), Na+/Taurocholate cotransporting polypeptide (NTCP), and monocarboxylate transporters (MCTs) [4,49,57,58]. Adding additional complexity, the metabolism of T4 and T3 is regulated by 3 selenoenzyme iodothyronine deiodinases (Ds: D1, D2 and D3) [59][60][61]. On the other hand, the congenital hypothyroidism can cause the following [49,[62][63][64], (1) congenital heart diseases; (2) diastolic hypertension; (3) reduced cardiac output, stroke volume and a narrow pulse pressure; (4) dilatation and overt heart failure; (5) elevation in the systemic vascular resistance [65][66][67][68].…”

In Vivo Study of Epithelial Adhesion via E-Cadherin-β- and α- Catenin-small GTP-Binding Proteins under T3 Regulation

“…The role of THs and TRs on cell proliferation and differentiation is not homogeneous. Cell response to THs, strongly depends on cellular context, that is, on the cell-type, ontogeny (progenitor or differentiated cell) and physiological state (normal or tumoral cell) [90]. Thus, the amphibian gastrointestinal remodeling comprises a first phase of cell apoptosis and then a burst in cell proliferation and differentiation.…”

“…Under the actions of increasing levels of THs and TRβ at the metamorphic climax, the lamina propria becomes thicker and permeable. This permeability promotes that both the differentiated and a few proliferating larval epithelial cells lose their contact at basal lamina, and that large numbers of cells undergo apoptosis [90]. Surprising, not only macrophages removal the apoptotic larval epithelial cells but also itself participate in the removal of their apoptotic neighbors even though they themselves are destinated to eventually die [35].…”