Life without thyroid hormone receptors

摘要: Thyroid hormone (TH) has many important functions during development and in the adult individual. It reaches its target cells via blood system binds receptor (TR) located within cell nucleus where regulates genes. This hormone-mediated gene regulation is a finely tuned interplay of numerous parameters. These include i) usage several isoforms receptors (TRα1, TRβ1, TRβ2, TRβ3) encoded for by two distinct genes, ii) receptor-mediated repression expression absence activation presence T3, iii) enzymatic control relative concentrations active thyroid (T3) versus prohormone (T4) through deiodinase activity. There are also genes that respond opposite way to T3. thesis describes mice live without TRs. What have we learned from them? The show milder phenotype than with congenital incapacity producing In contrast not having being TRs less severe. due ability act as potent transcription factors hormone. devoid all known were generated lacking either TRα or TRβ gene. Since deficiency single TR resulted much weaker compared fully deficient animals, our data indicate can substitute each other variety physiological developmental functions. Despite importance life possible However, leads an extreme dysregulation T3 retarded growth. skeletal development. acts growth (GH) insulin-like factor 1 (IGF-1). whether it direct effect on bone been subject controversy. exhibit combined low levels GH IGF1. Supplementing normalises growth, suggesting caused production IGF-1. defective ossification epiphyses was rescued GH, which supports hypothesis exhibits bone. Effects brain clinically neurologic cretinism derived foetal almost vegetative life. effects extensively studied particularly cerebellar We therefore aimed determine if any brain. Assaying solely rapid responses cerebrum, found 150 responding notably, third these observed no