ONTOGENY OF THYROID-HORMONE RECEPTORS AND C-ERBA EXPRESSION DURING BROWN ADIPOSE-TISSUE DEVELOPMENT - EVIDENCE OF FETAL ACQUISITION OF THE MATURE THYROID STATUS

We have determined the developmental changes in thyroid hormone recept or expression and thyroid hormone status in rat brown adipose tissue ( BAT). The present study demonstrates that c-erbAalpha and -beta genes are expressed in the developing BAT. The 6.5-kilobase (kb) beta1, 2.6- kb alpha2, 5.5-kb alpha1, and 6.6-kb a transcripts showed peak values on day 20 of fetal life. High affinity T3-binding sites were found in fetal BAT. Binding capacity was similar (18-day-old fetuses) or higher (20-day-old fetuses) than in postnatal or adult brown fat. In contras t, T3 receptors were scarce in fetal liver, and values in adult liver were similar to those in fetal BAT on day 20. The profiles of iodothyr onine 5'-deiodinase, nuclear T3 content, and receptor occupancy also s howed peak values in fetal BAT on day 20, but they were very low in fe tal liver. Thus, BAT has already achieved complete maturation of its t hyroid status on day 20 of gestational age. This highly tissue-specifi c developmental pattern is unique among other mammalian thyroid-sensit ive tissues studied to date. Between days 18 and 20 of rat fetal devel opment, there is a specific induction of the uncoupling protein gene e xpression, the main marker of differentiated adipocytes. The results s uggest that thyroid hormones may be involved in the establishment of t he differentiated phenotype of the brown fat cell in fetal life.