The Effect of Thyroid Dysfunction and Fasting on Placenta Inner Ring Deiodinase Activity in the Rat*

Abstract

The placenta contains iodothyronine 5-deiodinase activity (P5-Dase) that probably acts on iodothyronines in the fetal circulation to convert T4 to rT3 and T3 to 3,3'-T2. Since thyroid status and fasting have profound effects on iodothyronine deiodinases in other tissues, the present studies were performed to determine if these perturbations affected P5-Dase. Control and treated rats were mated and killed near term on the 20th day of gestation. P5-Dase was determined in placenta homogenates enriched with dithiothreitol by measuring the conversion of T4 to rT3. In four of five studies, P5-Dase was similar in dams that underwent thyroidectomy (Tx) on day 7 of gestation and sham Tx dams. P5-Dase was not altered in dams that were treated with methimazole (MMI) to induce maternal and fetal hypothyroidism. Treatment of dams with supraphysiological doses of T4, beginning on the seventh day of gestation, did not significantly affect P5-Dase. In three of four studies, P5-Dase was similar in fed dams to values in dams fasted for the last 5 days of pregnancy. Placenta iodothyronine 5'-deiodinase activity (P5'-Dase) was also measured in some studies. P5'-Dase was not decreased in Tx rats and was modestly decreased in MMI-treated rats. However, the effect of MMI was not reversed by the administration of supraphysiological doses of T4, Tx, MMI treatment, and fasting all decreased hepatic T4 5'-deiodinase activity in pregnant rats. These results strongly suggest that thyroid status and fasting do not alter P5-Dase activity.

Thyroid Hormone Regulates Rat Placental Type III lodothyronine Deiodinase Activity by Inducing Kinetic Changes Different from Those in the Same Isozyme in Rat Brain.

“…concentrations, 13 nM and 1.3 iM T4. As in previous reports [13,14], the thyroid condition did not affect placental T4 5-D activity assayed at the higher substrate concentration, but enzyme activity determined at the lower substrate concentration was significantly increased in hyperthyroidism as was brain T4 5-D. These results suggest that placental T4 5-D activity is dependent on the thyroid condition.…”

“…As shown in Table 3, a reduction in the apparent Km of placental T3 5-D produced by hyType III 5-D in the rat brain is dependent on the thyroid condition, that is, increased in hyperthyroidism and decreased in hypothyroidism [15], whereas type III 5-D in rat [13,14] and human [26] placenta is independent of the thyroid condition. The mechanism responsible for this discrepancy in 5-D is obscure.…”

“…In previous studies showing that the thyroid condition had no effect on 5-D activity in placenta [13,14], the substrate concentration was much higher than the apparent Km of 5-D [19,27]. We therefore investigated placental T4 5-D activity in control and hyperthyroid rats by two substrate The phospholipid concentration is expressed as micrograms of phosphorus per ml.…”

“…Although a recent report demonstrated that this enzyme also contains selenocysteine as does type I enzyme [9], others suggested that it is not a selenoprotein [10][11][12]. Interestingly, type III 5-D in the placenta is independent of the thyroid condition [13,14], whereas that in brain is increased in hyperthyroidism and decreased in hypothyroidism [15]. The mechanism responsible for this discrepancy in type III enzyme is unknown.…”

Na+/I− Symporter and Type 3 Iodothyronine Deiodinase Gene Expression in Amniotic Membrane and Placenta and Its Relationship to Maternal Thyroid Hormones

“…D3 expression rate or half-life of the placental D3 is not known yet. A previous in vitro study suggested that placental D3 activity is not affected by hunger [28]. The role of iodothyronine deiodinases and thyroid hormones in the carbohydrate metabolism is subject of a recent debate [29,30].…”