Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.

Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa.

Maternal hypothyroxinemia in early pregnancy is often associated with irreversible effects on neuropsychomotor development. To evaluate fetal tissue exposure to maternal thyroid hormones up to midgestation, we measured total T(4) and free T(4) (FT(4)), T(3), rT(3), TSH, and possible binding proteins in first trimester coelomic and amniotic fluids and in amniotic fluid and fetal serum up to 17 wk. Samples were obtained before interruption of maternal-fetal connections. The concentrations in fetal compartments of T(4) and T(3) are more than 100-fold lower than those in maternal serum, and their biological relevance for fetal development might be questioned. We found, however, that in all fetal fluids the concentrations of T(4) available to developing tissues, namely FT(4), reach values that are at least one third of those biologically active in their euthyroid mothers. FT(4) levels in fetal fluids are determined by both their T(4)-binding protein composition and the T(4) or FT(4) in maternal serum. The binding capacity is determined ontogenically, is independent of maternal thyroid status, and is far in excess of the T(4) in fetal fluids. Thus, the availability of FT(4) for embryonic and fetal tissues would decrease in hypothyroxinemic women, even if they were euthyroid. A decrease in the availability of FT(4), a major precursor of intracellular nuclear receptor-bound T(3), may result in adverse effects on the timely sequence of developmental events in the human fetus. These findings ought to influence our present approach to maternal hypothyroxinemia in early pregnancy regardless of whether TSH is increased or whether overt or subclinical hypothyroidism is detected.

Transfer of maternal thyroxine (T4) to the human fetus near term has recently been demonstrated. We investigated whether maternal thyroid hormone is available to the conceptus during the first trimester of pregnancy as well. Transvaginal ultrasound-guided puncture of the embryonic cavities was performed during the first trimester of pregnancy to obtain coelomic fluid between 6 and 11 weeks, and amniotic fluid between 8 and 11 weeks of pregnancy. T4 was found in coelomic fluid with mean values (+/- SEM) being 961 +/- 193 pmol T4/L (747 +/- 150 pg/mL). Concentrations increased both with gestational age and with rising maternal serum T4. Concentrations of 3,5,3'-triiodothyronine (T3) were at least 30 times lower, and those of 3,3',5'-triiodothyronine (rT3) four times higher, than coelomic fluid T4. Thyroxine and rT3 in amniotic fluid (8-11 weeks) were markedly lower than in the coelomic fluid, and T3 was undetectable. These results show that maternal thyroxine can cross the placental barrier as early as the second month of pregnancy. T4 from the coelomic fluid may reach the embryo via the yolk sac. This finding raises the possibility that the increase in maternal T4 occurring during the first trimester may be functionally important for the developing embryo, when its thyroid is not yet functioning.