Thyroid hormones fetal

Myxedema and goiter are the main conditions for which thyroid preparations are indicated. The treatment of cretinism is difficult because it is recognized only at or after birth. Even if this disease could be diagnosed m utero, thyroid hormones do not readily cross the placental barrier. In addition, the fetus, as does a premature infant, rapidly deactivates the thyroid hormones. The halogen-free analogue DlMlT [26384-44-7] (3), which is resistant to fetal deiodinases, may prove useful for fetal hypothyroidism (cretinism). 

Darnerud, P.O., Morse, D.C., Klasson-Wehler, E. et al. (1996). Binding of 3,3, 4,4 TCB metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice. Toxicology 106, 105-114. 

Adverse reproductive effects have been observed in animals fed PCB in the diet. Fetal resorptions were common, and dose-related incidences of terata were found in pups and piglets when females were fed Arochlor 1254 at Img/kg/day or more. Long-term low-level maternal exposure of rats before breeding and throughout gestation and lactation caused permanent hearing deficits, decreased serum thyroid hormones, and reproductive effects. PCBs have been observed in human cord blood and in tissues of newborn humans and animals. ... 

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, an increase in the thyroxine dose (about 30-50%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG levels and, therefore, elevated total T4 levels, adequate maternal thyroxine dosages warrant maintenance of TSH between 0.5 and 3.0 mll/L and the total T4 at or above the upper range of normal. 

Numerous animal studies and human clinical observations show that these hormones play an essential role in pre- and post-natal brain development in vertebrates. Thus, exposure to thyroid-acting agents during fetal life and early childhood, when normal levels of thyroid hormones are crucial to growth and neurological development, should be of greatest concern. 

Zoeller RT, Crofton RM. 2000. Thyroid hormone action in fetal brain development and potential for distribution by environmental chemicals. Neurotoxicology 21(6) 935-946. 

Simonian MH. ACTH and thyroid hormone regulation of 3 beta-hydroxysteroid dehydrogenase activity in human fetal adrenocortical cells. J Steroid Biochem 1986 25(6) 1001-6. 

The transplacental passage of maternal iodothyronines is quantitatively modest, although it might be sufficient to ensure adequate fetal development. Maternal thyroid hormone secretion is markedly increased during pregnancy (by 25-50%) thyroid therapy should therefore be carefully adjusted during pregnancy (58). 

Thyroid hormones Thyroxine Thyroid gland Fetal brain and bone development, oxygen consumption, gut motility... 

Fig. 5. Regulation of myosin heavy chains by thyroid hormones during development and in adulthood. T, represses the synthesis of the fetal /3 myosin heavy chain mRNA while inducing the expression of the adult a isomyosin mRNA.

The thyroidogenic effects and corresponding biochemical mechanisms of PCBs and other OHS were recently reviewed by Brouwer et al. [44]. The selective retention of certain OH-PCB congeners in blood (Sect. 5.2.2 and 5.3.2) is concomitant with effects observed on the plasma levels of thyroid hormones. Thyroxine is transported in plasma by a protein complex consisting of TTR and retinol binding protein (RBP). Rats administered CB-77 were shown to have reduced plasma levels of both thyroxine and retinol [196]. A major metabolite of CB-77, 4-OH-3,3, 4, 5-tetrachlorobiphenyl, was identified as the active compound [40]. The same hydroxy-PCB metabolite was found to be retained in mouse fetal soft tissue [191,197]. 

---