Brain development thyroid hormones, maternal

Iodine and thyroid hormones affect all stages of human development, from in utero life to adulthood. Iodine deficiency leads to insufficient production of thyroid hormones, which play a vital role in the process of early growth and development of many organs. During pregnancy, both maternal and fetal thyroid hormones are required for normal fetal brain development. Of them, maternal hormones constitute the main source in the first and the second trimesters, whereas the contribution of fetal hormones becomes more important in the third trimester (de Escobar et aL, 1985 Vulsma et ai, 1989). Many studies indicate that iodine deficiency and iodine-induced maternal-fetal hypothyroxinemia result in impairment of central nervous system (CNS) development during fetal and early postnatal life. 

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. 

Iodine deficiency at any degree of severity causes maternal and fetal hypothyroxinemia. As thyroid hormones of the mother and the fetus must be kept at optimal levels, iodine prophylaxis should be provided, especially in iodine deficient areas. To establish normal fetal brain development, iodine supplementation must be started before pregnancy and should be continued during the gestational period. 

Thyroid hormones, T3 and T4, have been i cwn to play significant but poorly understood roles in development and differentiation of rodent and human brain (1-7). In the human, disorders of maternal and fetal thyroid function include maternal and secondary fetal iodine deficiency, maternal hypothyroidism or hyperthyroidism, as well eis disorders related to deficient fetal autcxiomous thyroid hormcaie secretion, i.e., goiter or i radic oongenitel hypothyroidism. These disorders are identifiable causes of mental retardation (4, 8, 9, 10), cer ral peilsy (11, 12), and other significant neurological abnormalities (5, 6, 11) ... 

These observations suggested that normal brain development requires the availability of both maternal and fetal thyroid hormones,a suggestion which is at variance with earlier reports (9) (14) (15) (16) that the placenta in many mammalian species is relatively impermeable to thyroid hormones and with the suggestion (17) (18) that early mammalian development takes place normally in the absence of thyroid homrones. The observations do agree however with a more recent report (19) that rat embryonic tissues are provided with T and T3 only four days after uterine implantation and well before the onset of fetal thyroid function at 17 days. y also supported by the work of Woods et al (20) who showed that T and T3, when injected into pregnant rats, entered the rat... 

Bonet and Herrera and Esa ar et al have recently reported that thyroid hormones cross the placenta from dam to fetus and that maternal hypothyroidism does affect fetal growth and development and brain T3 cc itent. Further studies in the rat and other species, inclxiding man, will further clarify this question. 

The data suggesting the direct role of elemental iodine on brain development is the observation that correction of iodine deficiency in mothers prevents the emergence of neurological cretinism only if correction takes place before or during early gestation, thus before the onset of fetal thyroid function (83). What we would like to know in greater detail is which parameter is corrected in the human fetus when maternal iodine deficiency is corrected before the onset of fetal thyroid function Is it the fetal deficiency in iodine, in thyroid hormones or in both ... 

R.P. Ekins, A.K. Sinha and R.J. Woods, Maternal thyroid hormones and development of the foetal brain, 3 Iodine nutrition, thyroxine and brain development", N. Kochupillai, M.G. Karmakar and V. Ramalingswami eds., Tata McGraw-Hill Publ., New Dehli (1986), pp. 222-245. 

Escobar del Rey F, Mallol J, Pastor P, Morreale de Escobar G, Effects of maternal iodine deficiency on thyroid hormone economy of lactating dams and pups maintenance of normal cerebral 3,5,3 -triiodothyrone concentrations in pups during major phases of brain development. Endocrinology 121 803 (1987)... 

P.O.D. Pharoah, K.J. Connolly, Maternal thyroid hormones and fetal brain development, in "Iodine and The... 

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