Skip to main content

Table 3 General summary about the developmental thyroid hormone mechanisms (deiodinases, transporters, sulfotransferases and receptors) in human, rat and chicken [16]

From: Hypothyroidism and brain developmental players

Human Rodent (rat) Chicken
Week post conception Day post conception Incubation day
1 W - D3 is detected in uterine wall. 1 GD D2 and D3 are observed in uterine wall. 5 h (blastula stage) - TRα mRNA is noticed and the levels markedly increased during neurulation.
3 W - Thyroid gland begins. 7 -8.5 GD - Time of implantation process. 24 h - mRNA levels of D1, D2, and D3 are detected in whole embryos.
- Very high D3 activity is detected in decidual tissue.
4-6 W - TBG is observed in thyroid follicle cells at GD 29. 9 GD - Thyroid gland is first visible as an endodermal thickening in the primitive buccal cavity. 48 h - OATP1C1 expression appears.
- TRH is detected in fetal whole-brain at 4.5 weeks of gestation.   - TH is detected in rat embryotrophoblasts
- T4 is transferred via the placenta and has been found in the gestational fluid sac from 4 to 6 W.
5-11 W - Maternal-embryo transfer of THs has been detected in embryonic coelomic fluid and amniotic fluid.
- All the mRNAs encoding THTs are expressed in placenta from 6 W and throughout pregnancy.
8 W - T4, T3 and rT3 are detected in coelomic/amniotic fluids. 10 GD - T4, T3 and TRβ are detected in embryo/trophoblast unit. E2-E4 - T3, THTs, Ds and TRs are expressed in whole embryos.
- TRs, D2 and D3 are noticed in fetal brain.
10 W - TSH is first detected in the fetal pituitary. E4 - OATP1C1 expression is more than 10-fold higher in the telencephalon and diencephalon compared to the mesencephalon and rhombencephalon.
- D2 mRNA levels are highest in the diencephalon.
8-10 W - The fetus is able to produce THs during this period, but prior to that time, is totally dependent on maternal THs. E5 - TRα mRNA is widely distributed in fore-, mid- and hind-brain.
11 W - TBG levels are detected in fetal serum and increased through gestation. E6 - T4 and T3 are detected in embryonic brain.
8-11 W - TRH is detected in fetal hypothalamus. E7 - D2 activity is observed in the brain before the onset of thyroid function and increases significantly.
12 W - T4 and T3 are observed in serum and brain. 13 GD - Placental circulation established. E8 - D2 mRNA is noticed in cell clusters throughout the brain, particularly in rhombencephalon.
- Total serum T4 and T3 are low, free T4 is relatively high.   - TRs and TH are observed in fetal brain.   - OATP1C1 levels are declined substantially in all brain regions.
- rT3 is noticed in serum relatively high.   - D3 and D2 are detected in uterus and placenta.
- TH synthesis begins in fetal thyroid.
- Decreased mRNA expression of OATP1A2 but no change for OATP4A1 at 9–12 W compared to term.
14 W - Expressions of mRNAs encoding MCT8, MCT10, OATP1A2 and 14 GD - TRH mRNA is detected in neurons of the fetal hypothalamus. E4-E8 - D3 mRNA levels are markedly different in the telencephalon and diencephalon but remain stable, while the levels in mesencephalon and rhombencephalon show a sharp decrease and increase, respectively, during these days.
LAT1 are significantly lower prior to 14 W compared to term
15 GD - Pituitary TSH mRNA expression begins. E9-10 - Several elements of the TH action cascade are observed in the brain of embryos long before their own thyroid gland starts hormone secretion.
- TRH mRNA is detected in the developing paraventricular nuclei of the hypothalamus.
16 W - D3 is observed in placenta and fetal epithelial cells. 16-19.5 GD - TRs are observed in liver, heart and lung. E10 - The thyroid gland is fully functional.
- D3 and TRs are detected in fetal liver.   - D1 and D2 are noticed in fetal tissues.
- D1 is noticed in heart and lung.   - TRH is produced in low levels in hypothalamus and increases approximately threefold by GDI9.5.
- Significant fetal TH secretion begins.
16-20 W - Duplication of TBG concentrations. 17 GD - TH synthesis begins in fetal thyroid E13 - Brain D2 is elevated at the peak of neuroblast proliferation.
- TSH protein and Sulfotransferase are observed.
18 -22 GD - The total T4 and T3 concentrations in fetuses are increased dramatically because of maturation of hormone synthesis of the fetal thyroid gland. E14 - The strong increase in intracellular T3 has been observed.
- The coordination between THTs and Ds is regulated both transplacental TH passage from mother to fetus and the development of the placenta itself through the progress of gestation.
20 W - A steady increase in serum TH levels begins and continues to term. 19 GD - Significant fetal TH secretion begins. E15 - Plasma T4 levels start rising markedly around this day.
- Marked rise in serum TH but levels at birth still below those in adult.
22-32 W - Serum total and free T4 and T3 near and below adult levels, respectively. 22 GD - Birth state. E16 - The decrease in DI activity in gonads is combined with the relatively high D3 activity.
- Thyroid system is less developed.
- The HPT axis begins to mature during the second half of gestation.   - As much as 17.5% of THs found in the newborn are of maternal origin.   - A significant increase in T3 production and in D2-activity and -mRNA expression are combined with a decreased in D3 activity.
- LAT1 and OATP4A1 have been localized only during the third trimester.
40 W - Birth state. 10 PND - Brain development equivalent to human birth. E13/14–E17 (synaptogenesis) - Brain D2 activity is moderately elevated, whereas D3 activity and mRNA expression are highest between these days, followed by a dramatic decrease thereafter.
- Complete maturation of thyroid system.
- MCT8 has been localized in the placenta in all three trimesters of pregnancy.
- High concentrations of the different iodothyronine sulfates, T4S, T3S, rT3S and T2S, have been documented in human fetal and neonatal plasma as well as in amniotic fluid during the pregnancy. 10-20 PND - Serum TH levels continue to rise and are higher than adult levels between these days. E18 - D1 and D3 are expressed in the granule cells, whereas D2 is found mostly in the molecular layer and the Purkinje cells at that time.
14-50 PND - The levels of pituitary and serum TSH slowly decrease from PND 14–16 until reaching adult levels at PND 40. E19 - The increase in brain T3 production correlates with the appearance of TRβ expression in the cerebellum, telencephalon and optic lobes.
- TRH levels increase to adult levels by PNDI7–29, then decrease transiently between PND 31–41; adult levels are once again reached at PND 50.
E20 (at the moment of pipping) - The brain is quite well developed at the time of hatching.
- Adult TRH mRNA expression patterns are observed at PND 22.   - The gradual increases in plasma T4 and hepatic D1 are detected.
- D3 levels are decreased in spleen and increased in skin and the lungs towards hatching.
- T3 production seems to be elevated markedly in liver.
- The rise of T4 is much more pronounced than in plasma.
- Diminished T4 sulfation is detected.
30 PND Complete maturation of thyroid gland. E14-E19/20 - The T3 breakdown capacity by D3 is high in liver but low in kidney.
E15/16-E20 - T4 levels in plasma increase gradually during these days.
- In contrast to TRα expression which increases gradually towards hatching, expression of TRβ shows an abrupt elevation in late development, especially in the cerebellum.
- The majority of tissues express D3 together with either D1 or D2.
E17-E20 - The levels of D3 activity noticed in liver are rapidly drop by more than 90%.
- D1 levels in testis and ovary strongly decrease around hatching.
E18–E20 - Brain D2 activity is moderately decreased, whereas D3 activity is low.
E19-E20 - The low T3/T4 ratio is associated with high T3 breakdown in liver and with high T4 inactivation or T3 secretion in kidney.
E20-C0 - D1 activity gradually increases, reaching a maximum around these period, and decreases slowly to posthatch levels thereafter.
C1 (first day posthatch) - The expression of D1 is limited to the mature granule cells and that of D3 to the Purkinje cells exclusively, whereas D2 remains clearly noticed in the molecular layer.
C2 - Highest D1-activities and -mRNA expressions are detected in the liver, kidney, and intestine.
C1-C7 - The circulating T3/T4 ratio started to increase gradually during the first week after hatching.
  1. - Abbreviations: W is week, GD is gestation day, E is incubation day, PND is postnatal day, C is posthatch day, THs is thyroid hormones, TRH is thyroid releasing hormone, TSH is thyroid stimulating hormone, THTs is thyroid hormone transporters, MCT is monocarboxylate transporter, OATP is organic anion transporter, Ds is deiodinases (D1, 2, 3), TRs is thyroid hormone receptors (TRα, β), T4 is Thyroxine, T3 is triiodothyronine, rT3 is reverse triiodothyronine, T2S is diiodothyronine sulfate, T3S is triiodothyronine sulfate, T4S is thyroxine sulfate, rT3S is reverse triiodothyronine sulfate, HPT is hypothalamic-pituitary-thyroid axis and TBG is thyroxin binding globulin.