Iodothyronine placenta

Evidence has accumulated for the existence of a specific deiodinase for the inner ring of iodothyronines which is further distinguished from the type I enzyme because of its insensitivity to sub-mM PTU concentrations. Thus, type III iodothyronine deiodinase converts T4 to rT3 but not to T3 and produces 3,3 -T2 from T3 but not from rT, (Table I). It has been detected in chick embryo heart [94] and liver [95] cells, monkey hepatocarcinoma cells [96], rat CNS [71,75,97], human [98], rat [98] and guinea pig [99] placenta, and rat skin [100], With higher enzyme activities in cerebral cortex than in cerebellum, the distribution of the type III deiodinase is different from that of the type II enzyme [75], In brain cell cultures type III deiodination appears associated with the presence of glial cells [76,78,79],... 

To confirm the maternal origin of the iodothyronines found in early embryonic samples, we determined their concentrations in fetal tissues obtained from normal (C) mothers and from dams which had been thyroidectomized (T) a few months before mating 20. When the embryonic samples were obtained from T mothers, concentrations of both T4 and T3 were below the limits of detection in all tissues, placentas included, at least up to 17 gd (Fig. 2 A). 

Homogenates of rat and human placentas actively deiodinate T4 and T3 in the tyrosyl (5) ring, generating rT3 from T4 and 3,3 -T2 and 3 -Ti from T3 (Figure 1). rT3 generated from T4 or rT3 added directly to the homogenates was not further deiodinated. This 5-deiodinase activity was in the microsomal fraction and was protein, pH, time, and DDT dependent. The effects of PIU, iodothyronines and other agents on placental microsomal 5-deiodinase activity were assessed. The apparent Michaelis-Menton (%) for the deiodinase in human placental microsomes was 1.2 x I0 m. T3, 3,3 -T2, iopanoic acid (lA),... 

Figure 2. The inhibitory effect of iodothyronines (3,5,3 -T3 and 3,5,-T2), i( )anoic acid, prcpranolol, and the sulfhydryl oxidizing agents (iodoacetic acid, diamide, and PIU) on inner ring iodothyronine deiodinase activity in the microsomal fraction of human placenta. The T4 concentration was 6.4 x 10" M. The incubation time was 60 min.

Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, studies were performed to determine if these perturbations affected 5-deiodinase activity. C3ontrol and treated rats were mated and killed near term on the 20th day of gestation. 5-deiodinase activity was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of 5 studies, 5-deiodinase activity was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and... 

Differiences in placentation among species may determine (diether the placenta is also a site for peripheral deiodination of maternal iodothyronines. In the hemochorial placenta, maternal and fetal blood is in direct contact with placental tissue. therefore, in these placentas, iodothyronines from both the maternal and fetal circulations are litely to provide substrates for inner ring deiodinase activity. Species with hemochorial placentation include the rat, guinea pig, and human. In the she, ihich has endotheliochorial placentation, only fetal blood is in contact with placental tissue. For this reason the placental deiodination of maternal iodothyronines in the sheep may be limited. 

Effect of propylthiouracil, iodothyronines, and other agents on thyroid hormone metabolism in human placenta. J. Clin. 

J.T. Hidal, and M.M. Kaplan, Characteristics of thyroxine 5 -deiodination by cultured human placenta cells. Regulation by iodothyronines. J. Clin. Invest. 76 947 (1985). 

The other major role of selenium is in the production of the thyroid hormones (see p. 127), for which it is a component of the enzyme type I iodothyronine deiod-inase (IDi), which convertsT4 to the physiologically activeT3.AVhen there is a deficiency of selenium the ratio ofT4 T3 increases. The enzyme is found primarily in the liver and kidney and not in the thyroid of farm animals. Type II iodothyronine deio-dinase (ID2) does not contain selenium and also converts T4 toT3, but as it is imder feedback control from T4 an increase in the latter, when selenium is deficient, compounds the problem. The major enzyme in ruminants is ID and in non-ruminants ID2. A third selenium-containing enzyme, ID3, has been found in the placenta. ID is particularly important in the brown adipose tissue of newborn ruminants and releases T3 for use in other tissues. 

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