Thyroid hormones in tissues from human embryos and fetuses

Abstract

This study was intended to quantify T3 and T4 in various human tissues at different stages of gestation as a contribute in the evaluation of the role of thyroid hormones in fetal development, particularly before the maturation of fetal thyroid function. Moreover, for a better comprehension of the influence of thyroid hormone status in tissues, the study was extended to adults. Embryonic specimens were obtained from voluntary abortions between 6 and 12 weeks of gestation, fetal and neonatal specimens from fetuses and neonates between 15 and 36 weeks of gestation after spontaneous abortion or stillbirth, and adult specimens from men (age range: 45-65 years) after death for cardiovascular diseases. Thyroid hormones were measured by the method of Gordon and coworkers. In embryos T3 and T4 were measured in limbs, carcasses, brain and liver: considering all values measured in the period 9-12 weeks, a mean concentration of 0.11 ng/g for T3 and 1.28 ng/g for T4 was obtained. In pooled limbs of 6-8 weeks T3 was barely measurable (0.01 ng/g). In the carcasses there was an increase in T3 and T4 concentrations of 40 and 20 times respectively from the 9th to the 12th week, when thyroid follicles organization takes place. In fetuses and adults T3 and T4 were measured in brain, heart, kidney, liver, lung, skeletal muscle and skin (mean concentrations: 0.86 ng/g for T3 and 7.44 ng/g for T4 in fetuses and neonates; 1.36 ng/g for T3 and 12.75 ng/g for T4 in adults). Hormones concentration increased with gestational age; the T3/T4 ratio increased until 22-24 weeks, when the prevalent increment in T4 occurs. T3 concentration up to 30 weeks was generally higher in tissues than in cord serum of the corresponding age. During the last month of gestation T3 increment was faster in serum. T4 level was always predominant in serum. In conclusion, T3 and T4 have been detected in the limbs of embryos before the onset of thyroid hormone secretion. Concentrations were 1/150 and 1/70, of the normal maternal blood values respectively. It is conceivable that these hormones are of maternal origin, and the question of whether such small quantities may play a role in fetal development is open.

Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction

“…Current evidence points to a direct role for maternal TH in human fetal CNS development from the 1 st trimester of pregnancy [4,5] and this necessitates the transplacental passage of 60 maternal TH to the fetus. Transplacental transport of maternal TH is evidenced by the finding of a biologically significant concentration of free thyroxine (T4) in fetal coelomic fluid and in fetal tissues from as early as five weeks of gestation [6,7]. Even at term, the concentration of maternally-derived T4 in the circulation of fetuses with absent endogenous thyroid function reaches 25-50% of normal [8].…”

The Relationship Between Thyroid Status, Cortisol Level, Cognition And Neuropsychiatric Symptoms In Patients With Alzheimer Disease

“…In addition, patients with AD have been shown to have significantly increased rT3 levels and an increased rT3 to T4 ratio in the CSF [33]. Taken together, these findings suggest abnormal intracerebral metabolism of THs and possibly brain hypothyroidism in AD [34]. Although the A high concentration of glucocorticoid receptors exists in the hippocampus, and this brain region is thought to be involved in the negative-feedback mechanism of glucocorticoid secretion [35].…”

Thyroid hormone affects embryonic mouse lung branching morphogenesis and cellular differentiation

“…It has been suggested that local tissue conversion to biologically active T 3 may occur in fetal tissues. T 3 nuclear receptors, binding of T 3 , and increasing binding capacity are all present in human fetal lung tissue at 12-19 wk of gestation and in other species at comparable times (6,13,18,23). Thus low levels of endogenous T 3 may play a role in lung morphogenesis during the early pseudoglandular period of lung development.…”

“…T3 levels in human embryonic lung are 0.5 nM, and the nuclear binding coefficients of T3 receptors in rodent embryonic lung have been shown to be 0.5 nM. A similar range of T 3 concentrations has also been used in cultured fetal lung and showed a dose-response effect on surfactant phospholipid synthesis (13,25,26,36). Cultured lungs were maintained at 37°C in 95% room air-5% CO2 for the 72 h of culture.…”

“…In particular, in rodent lung organ cultures and human lung explant cultures, triiodothyronine (T 3 ), the active form of thyroid hormone, influences late fetal lung development by accelerating epithelial cell differentiation leading to surfactant phospholipid synthesis and by regulating lung structural development and alveolar septation (9,11,26,38). Little is known about the cellular expression pattern of T 3 receptors during fetal lung development, but they are present in rodent and human lung tissue during the pseudoglandular period and increase in quantity and binding affinity as lung development progresses (6,13,18,20,23). Although there are relatively low levels of T 3 and its receptors in early fetal life, maternal hypo-or hyperthyroidism leads to characteristic changes in lung growth, morphology, and function (6,10,17,32).…”