Ontogeny of Plasma-Free Thyroxine and Triiodothyronine Concentrations during the Perinatal Period and Maternofetal Transfer of Thyroid Hormones in the Rabbit

Abstract

Although rabbit has been used as a convenient animal model in understanding the role of thyroid hormones during the perinatal development, ontogenetic changes in plasma-free thyroxine or triiodothyronine concentration has not been studied in this species. We delineated the ontogeny of immunoreactive plasma-free thyroxine and triiodothyronine concentration during the perinatal period. It is generally believed that thyroid hormones do not cross the placenta from the mother to the fetus in sufficient concentrations to exert biological effects in the fetus. We administered 250 pg/kg of thyroxine (T4) or 125 pg/kg of triiodothyronine (T3) intramuscularly to the rabbit doe on the 25th and 26th day of gestation. Maternal and fetal plasma-free T4, T3 and glucose concentration and fetal liver glycogen content were quantitated on the 27th day of gestation. Maternal and fetal plasma-free T4 and T3 concentration was significantly higher than the control in T4-treated animals. Maternal and fetal plasma T3 concentration was higher and free T4 concentration lower than the control in T3-treated animals. T3 or T4 treatment resulted in fetal hyperglycemia and depletion of fetal hepatic glycogen content. We conclude that T4 or T3 cross the rabbit placenta and exert thyromimetic effects in the fetus. A convenient animal model to investigate in utero effects of T4 or T3 in mammalian fetal development is proposed.

Maternal Treatments with Corticosteroids and/or T₃ Change Lung Volumes and Rupture Pressures in Preterm Rabbits

“…The dose that we used caused a signifi cant improvement in static pressure-volume curves of the preterm rabbit lungs [7]. In similarly treated preterm rabbits we found cord blood elevations in fetal T3 to over 500 ng/dl [19], values comparable to those re ported by others [6,7], The effects of mater nal T3 administration may not cause a pure T3 effect on the fetal lung because the moth ers become thyrotoxic and the fetuses be come hyperglycemic [7,19], While precursor incorporation into surfactant was found to be supraadditive in vitro [21,22], T3 antago nized the increased fatty acid synthesis and glycogenolysis noted with corticosteroids [11], Devaskar et al [7] found that T3 pre vented the runting seen with maternal corti costeroid treatment but did not cause an increased deflation stability above that seen with corticosteroid alone. They also noted increased death after delivery in sponta neously breathing newborns relative to ani mals that received corticosteroids alone [7], Our previous results indicated that T3 improved dynamic compliance very little, and the effect of surfactant on T3-treated fetal lungs was less striking than the effect of surfactant on corticosteroid-treated lungs [19].…”

“…The dose of T3 was chosen based on the reports of Devaskar et al [6] demonstrating placen tal transfer in the rabbit of high doses of T3 given to the mother, a result similar to that reported by Gross et al [5] in the pregnant rat. The dose that we used caused a signifi cant improvement in static pressure-volume curves of the preterm rabbit lungs [7].…”

“…The clinical results were sup ported by studies in animals showing in creased surfactant synthesis, improved lung pressure-volume relationships, and morpho logic maturation [3], Surfactant treatments of preterm infants at delivery also decreased the incidence and severity of RDS [4], How ever, neither surfactant nor corticosteroids prevented RDS, perhaps in part because some infants had lungs that were quite im mature structurally. T3 recently was shown to cross the placenta if given to pregnant rats or rabbits in high doses [5,6] and to in fluence fetal lung maturation by increasing deflation stability [7], In vitro T3 and corti costeroids have additive and synergistic ef fects on markers of lung maturation [8][9][10], However, simultaneous administration o fT 3 and corticosteroids to pregnant rats resulted in augmentation of some aspects of lung maturation and interference with other maturational responses induced by corticoste roids [5,11]. Nardell and Brody [12] re ported that the pressures at which postnatal rat lungs ruptured with saline inflation cor related with alveolarization and connective tissue changes in the lungs.…”

Altered Thyroidal States Modulate the Insulin Receptor Characteristics of the Developing Rabbit Brain

“…Although the developmental changes of reverse T3 separate from active T3 have not been delineated in the rabbit, recent studies reveal the neonatal serum total T3 concentrations to be similar to the fetal levels till day 4 of life. An increase in total T3 is observed starting day 4 and reaching a peak on day 7 of life [27]. Serum T3 concentrations in the rat neonate do not correlate with the brain T3 concentrations, the former being dependent on production and clearance of T3 [28].…”