Endocrine Abstracts

Thyroid hormone is critically important for many developmental processes. However, less is known about how this hormone elicits its actions, a question that becomes more puzzling given that that distinct target tissues respond in different ways and often at different times. How does this systemic hormonal signal elicit its diverse responses? Targeted mutagenesis of thyroid hormone receptors (TR) encoded by the Thrb and Thra genes has indicated that some specificity is conferred by distinct TR isoforms. Our recent studies have focused on sensory systems, a previously little-studied area of thyroid hormone action. As shall be discussed, these systems reveal the versatility of thyroid hormone signaling as well as unexpectedly novel functions. The auditory system provides a complex paradigm in which thyroid hormone and TRb coordinate the differentiation of multiple cochlear cell types. TRb is expressed in early embryonic cochlea but the phenotypic defects only become evident postnatally, suggesting that factors other than TRb control developmental timing. Type 2 deiodinase (Dio2) which converts thyroxine (T4) into tri-iodothyronine (T3), the major ligand of the receptor, is induced in postnatal cochlea. Dio2−/− mice are deaf suggesting that the cochlea stimulates its own maturation by amplifying T3 levels locally to prompt the onset of hearing. The colour visual system is a novel target in which thyroid hormone acts primarily on a single critical cell type in the retina, the cone photoreceptor. Mice lacking the TRb2 isoform exhibit a form of colour-blindness. Cones normally express opsin photopigments for sensitivity to short (S, blue) or medium (M, green) wavelengths of light but in TRb2−/− mice, M opsin is lost. Thus, a thyroid hormone receptor diversifies cones into the S and M subtypes necessary for color perception. Evidence also implicates deiodinases in cone development.