Thyroid hormone receptors, cell growth and differentiation

Background: Tissue homeostasis depends on the balance between cell proliferation and differentiation. Thyroid hormones (THs), through binding to their nuclear receptors, can regulate the expression of many genes involved in cell cycle control and cellular differentiation. This can occur by direct transcriptional regulation or by modulation of the activity of different signaling pathways. Scope of review: In this review we will summarize the role of the different receptor isoforms in growth and maturation of selected tissues and organs. We will focus on mammalian tissues, and therefore we will not address the fundamental role of the THs during amphibian metamorphosis. Major conclusions: The actions of THs are highly pleiotropic, affecting many tissues at different developmental stages. As a consequence, their effects on proliferation and differentiation are highly heterogeneous depending on the cell type, the cellular context, and the developmental or transformation status. Both during development and in the adult, stem cells are essential for proper organ formation, maintenance and regeneration. Recent evidence suggests that some of the actions of the thyroid hormone receptors could be secondary to regulation of stem/progenitor cell function. Here we will also include the latest knowledge on the role of these receptors in proliferation and differentiation of embryonic and adult stem cells. General significance: The thyroid hormone receptors are potent regulators of proliferation and differentiation of many cell types. This can explain the important role of the thyroid hormones and their receptors in key processes such as growth, development, tissue homeostasis or cancer. This article is part of a Special Issue entitled Thyroid hormone signalling. (C) 2012 Elsevier B.V. All rights reserved.