Mechanism of action of thyroid hormones during chick embryogensis

Abstract

SYNOPSIS. In order to better understand the action of thyroid hormones in chick embryo, we have studied their binding to cellular receptors from target tissues, the interaction of thyroid hormone-receptor complex with DNA and their effect on the synthesis of various mRNAs.Target tissues contain nuclear receptors which specifically bind L-thyroxine and L-triiodothyronine. L-triiodothyronine binds to a single receptor, which is a non-histone protein of Mr = 60,000 d with a sedimentation coefficient of 3.8S. Its association constant is 109-1010 M-1 and its maximal binding capacity varies between 0.8 and 3.1 fmoles/μg DNA, according to the tissue and age of the embryos. L-thyroxine is bound to two sites. The first site has a binding capacity similar to that of the L-triiodothyronine receptor, but its association constant is of 108 M-l, whereas the second site has a low affinity and a rather large capacity. Both high affinity sites for L-triiodothyronine and L-thyroxine sharply increase in target organs between the 9-12 days of incubation, when the embryo is growing fast.We have also found that during the same period of maturation, the hormone-receptor complex binds tightly to DNA, a step which is necessary to initiate transcription. Furthermore, thyroid hormones influence several mRNA sequences in developing brains, as shown by the decrease or disappearance of translated proteins in hypothyroid embryos. These findings confirm the essential role of thyroid hormones as regulators of transcription of specific mRNA during fetal growth.The resemblance of the binding properties and ontogenic patterns of the high affinity sites for the two hormones suggests that they are the same, single site having different affinities for the two hormones. The presence of such a site at day 9-12 of embryogenesis, when little or no L-triiodothyronine is produced, indicates that L-thyroxine plays the main metabolic function during this critical phase of development. © 1988 by the American Society of Zoologists.