Ribosomal protein synthesis in 16 and 19 day gestation fetuses of hypothyroid mothers

Thyroid hormones are transported across the placenta. Thyroid hormone receptors are present in the midgestation rat fetus and fetal tissues selectively accumulate thyroid hormones prior to the onset of fetal thyroid function. It has not been demonstrated adequately that maternal thyroid hormones are essential for early fetal physiologic functions and neurological development. The present study compares the effects of maternal thyroid hormone versus fetal thyroid hormone on the regulation of rRNA and ribosomal protein synthesis in the developing fetus. This was accomplished by first comparing 16-day gestation (just prior to the onset of fetal thyroid function) fetuses of control and hypothyroid mothers. Then 19-day gestation (fetal thyroids are functional) fetuses of control and hypothyroid mothers were compared as development of fetal thyroid function lags in hypothyroid mothers. Rats made hypothyroid (Tx) by radiothyroidectomy were given replacement doses of thyroxine (T4) until the day that they were placed with a male for mating. Control, Tx and growth hormone (GH)-treated Tx dams and their fetuses were sacrificed on either the 16th or 19th day of gestation. Ribosomes (r) were isolated from placentas and from fetal brains and livers and rRNA, total 14C-leucine incorporation, and 14C-leucine incorporation into ribosomal protein per microgram of rRNA were determined. On the 16th day of gestation, prior to the onset of fetal thyroid function, all three of the above metabolic parameters were reduced significantly below control levels in the placentas of Tx rats and in the brains and livers of their fetuses. This was true also for the fetal brains and livers of GH-treated Tx mothers. Development of fetal thyroid function lags in the Tx mother. rRNA, total 14C-leucine incorporation, and 14C-leucine incorporation into ribosomal protein per microgram of rRNA continue to be significantly depressed in these fetal tissues and placentas of Tx rats on the 19th day of gestation. In fact, brain protein synthesis falls further behind in fetuses of Tx dams at this gestational age when compared with control fetal brains. These data support the hypothesis that maternal thyroid hormones are important, by at least midgestation, for normal fetal physiologic development and support the concept that appropriate maturation of the fetal pituitary-thyroid plays a role in fetal brain protein synthesis and therefore neurological development.