Maternal hormones fetal thyroid function

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... 

Rey, F. Effects of maternal hypothyroidism on weight and thyroid hormone content of rat embryonic tissues,before and after onset of fetal thyroid function. Endocrinology 117 1890-1900 (1985). 

Work performed by Weiss and Novak 5 and by Sweney and Shapiroi strongly suggested the possibility that maternal thyroid hormones are available to the rat embryo before onset of fetal thyroid function, despite opinions to the contrary 1 . We decided to re-investigate this possibility by measuring T4 and T3 concentrations in embryonic and fetal tissues. We had developed specific and sensitive RIAs 18, and extensive extraction and purification... 

CONTRIBUTION OF MATERNAL HORMONES AFTER ONSET OF FETAL THYROID FUNCTION. 

Table 1 outlines the experimental design which we used. Methimazole (MMI) was used to block maternal and fetal thyroid function. Some of the MMI-treated dams received a replacement dose of T4 given by constant infusion, as described in detail elsewhere23. The main findings are summarized in Fig. 5, which shows the T4 and T3 concentrations in fetal carcass and brain. Comparison of the hormone levels in fetuses from C + MMI + T4 (or T + MMI + T4) dams with those from C + MMI (or T + MMI) mothers shows that infusion of T4 into the mothers not only ameliorates fetal deficiency of T4, but also of T3. This occurs without an increase of fetal plasma T3, suggesting that the fetal brain derived its T3 from local deiodination of T4. 

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 ... 

Therefore, based on the above Hmited evidence, we conclude that excess iodine exposure may influence maternal-fetal TH metabohsm by three mechanisms (1) excess iodine affects the maternal hormone thyroid level by inhibition of thyroid function and/or Dl activity (2) excess iodine has an effect on maternal—fetal TH transfer by affecting placental D2 and D3 activity and (3) excess iodine transferred by the placenta has a direct inhibition on the development and function of the fetal thyroid gland (Figure 88.2). 

Thus, under conditions of severe and chronic ID the developing embryo is thyroid hormone deficient both before and after onset of its own thyroid lunction. Before thyroid function embryonic and fetal tissues are entirely dependent on the maternal iodothyronines for their supply of thyroid hormones. As a result of the maternal hypothyroxinemia, the T4 available to the developing LID embryo and fetus is very low. The supply of T3 becomes increasingly deficient. 

Functionally iodine is important because of its role in the synthesis of the thyroid hormones and it has been postulated that hypothyroidism, either maternal or fetal, or even elemental iodine... 

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