Deiodinase placental

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). 

Salvatore D, Low SC, Berry M, et al. Type 3 Iodothyronine deiodinase Cloning, in vitro expression, and functional analysis of the placental selenoenzyme. J CUn Invest 1995 96 2421-2430. 

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),... 

In addition to iodothyronine 5-deiodinase activity, placental hoanogenates and cultures of human chorionic decidual cells contain T4 and rT3 5 -deiodinase activity but this activity is far less than that observed for 5-deiodinase. 

Figure 3. Ihe ontogenesis of rat placental homogenate 5-deiodinase. Results are es ressed as a percentage of the maximal value of rT3 generated from T4 from days 14-20 of pregnancy.

It can be postulated that placental deiodinase activity has two effects on mtemal-fetal thyroid economy. Ihe first is that the placenta is a site for "peripheral deiodination" in the matemcd euA/or fetal circulation. Ihe meaning of "peripheral deiodination" in this discussion is restricted to the situation in which products of deiodinaticai are returned to the compartment from vhich the precursor... 

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. 

Ihe second possible effect of placental deiodinase activity on maternal-fetal thyroid econoty is that substrates from one cxanpartment are deiodinated and the products transferred into a second ocnpartment vhich also borders the deiodinating tissues. For exanple, mat nal plasma T4 may be deiodinated by the placenta and a portion of the rT3 generated transferred to the fetal vascular pool. According to this schema, fetal T4 could also be the source of some rT3 in maternal serum. In addition, as discussed earlier, maternal rT4 could contribute to AF rT3 by virtue of deiodinase activities in the chorion and amnion. 

Human placental thyroxine inner ring deiodinase in ccmplicated pregnancy, Metabolism 34 535 (1985). 

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