Thyroid hormone (T3) works through nuclear receptors which are encoded by two genes TRalpha and TRbeta. Each gene encodes several isoforms among which some are not true receptors as they do not bind to DNA or do not bind thyroid hormone. In the absence of T3, thyroid hormone the receptors (apo-receptors) behave as transcription repressors toward target genes. Upon binding the hormone, the apo-receptors are transformed into holo-receptors which work as tanscription activators. This model assumes that the absence of T3 should have much more detrimental effects than the absence of receptors. The use of genetically modified mice has indeed shown that the model of apo-receptor has a physiologic relevance in hypothyroid animals. Moreover we will show that natural situations exist during fetal and post natal development where apo-receptors naturally play a physiologic role for the proper development of organs.
These data suggest then that the local availability of T3 is determinant for the genetic program controlled by thyroid hormone receptors. Data obtained from genetically modified mice show that this model of local distribution of the hormone is valid during the development of several tissues in the mouse.
Then thyroid hormone is playing crucial roles during development as well through its presence as through its absence.
22 - 24 Mar 2004
British Endocrine Societies