Endocrine Abstracts

Thyroid hormone receptors are ligand dependant transcription factors. They mediate a genomic response initiated by the thyroid hormone triiodothyronine, T3.

In mice and humans two isotypes, TRα and TRβ, are produced from two different genes, and several isoforms of each isotype are present in the tissues. The knock out of either TRα or TRβ genes induces different phenotypes and several studies led to the conclusion that the TRα receptor plays a major role in the development and maturation of many tissues during the fetal to neonatal transition.

In the absence of T3 unliganded TRα (so called apo-receptors) work as transcription repressors. Combination of mutations that abrogate either the production of the receptors and/or the production of thyroid hormone allowed dissecting the physiological roles of apo-receptors in vivo.

We have shown that during fetal development and in hypothyroid pathological conditions in adults, TRα are under the configuration of apo-receptors and repress development of heart and erythropoietic tissues. At birth the surge of thyroid hormone transforms these apo-receptors into holo-receptors ensuring the normal postnatal development of these tissues.

Then the switch from apo to holo-receptor plays a major role in controlling normal development at the transition between fetal and neonatal life and in hypothyroid pathological conditions in the adult.