Developmental regulation of thyrotropin receptor gene expression in the fetal and neonatal rat thyroid: Relation to thyroid morphology and to thyroid-specific gene expression

The TSH receptor plays a pivotal role in thyroid gland function, growth, an d differentiation, but Little is known about its role or regulation in the fetus and neonate. To explore these questions, we systematically evaluated TSH receptor gene expression at the level of messenger RNA (mRNA) in thyroi d glands obtained from rat fetuses and neonates, from 14 days gestation to day 5 of postnatal life. Results were compared with histological evidence o f differentiation and to thyroid-specific gene expression. Northern blot an d RT-PCR analysis revealed that TSH mRNA was first detected at low levels o n fetal day 15, but it increased 3- to 15-fold on fetal days 17-18. Up-regu lation of TSH receptor mRNA on fetal day 17-18 was accompanied by the first appearance of colloid formation and of follicular development on morpholog ical examination. It was also paralleled by increased expression of the thy roid-specific genes thyroglobulin (Tg) and thyroid peroxidase. Unexpectedly , TSH mRNA abundance was 2- to 3-fold higher in pregnant dams than in nonpr egnant adult females or adult males. In view of the 8-day lapse between the first appearance of the thyroid dive rticulum and up-regulation of TSH receptor gene expression, we conclude tha t pituitary TSH, acting through its receptor, plays an important role in te rminal thyroid maturation, but it is not involved earlier in gestation. Sim ilarly, these data support previous evidence that the weak thyrotropic acti vity of human CG could not be of significance in early fetal thyroid gland development. The increased TSH receptor mRNA on fetal day 17-18 may be attr ibutable to up-regulation by TSH, which is first secreted into the fetal ci rculation at this time. The significance of the increased TSH receptor expr ession during pregnancy remains to he explored.