Placenta deiodination

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],... 

Type III deiodinase catalyzes the conversion of T4 to reverse T3, and the conversion of T3 to T2- These steps constitute 5 -deiodination reactions. The enzyme occurs in the brain and skin of rats. The physiological role of the type III enzyme is thought to be to protect the brain from possible toxic effects of active thyroid hormone (T3). The placenta is distinguished in that it contains both type II and type III deiodinases (Glinoer, 1997). 

Three types of deiodinases are currently known, and these are distinguished from each other primarily based on their location, substrate preference, and susceptibility to inhibitors. Type I deiodinase is found in liver and kidney and catalyzes both inner ring and outer ring deiodination (i.e., T4 to T3 and rTs to 3,3 -T2). Type II deiodinase catalyzes mainly outer ring deiodination (i.e., T4 to T3 and T3 to 3,3 -T2) and is found in brain and the pituitary. Type III deiodinase is the principal source of rTs and is present in brain, skin, and placenta (14). 

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),... 

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. 

Roti, S.L. Fang, K. Green, C.H. Emerson, and L.E. Braverman, Human placenta is an active site of thyroxine and 3,3, 5-triiodothyronine tyrosyl ring deiodination. J. Clin. Endocrinol. Metab. 53 498 (1981). 

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). 

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