Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase

Abstract

Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3′,5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.J. Clin. Invest. 103:979-987 (1999).

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

“…Similar to a number of previous studies, we detected D3 expression in human amniotic membrane tissue samples [11,13,22]. These results suggest that in addition to the placenta and the uterus, the amniotic membrane, which expresses D3, may also regulate the transfer of thyroid hormones from the mother to the fetus in term pregnancy [13].…”

“…The uterus, placenta, and other maternofetal interfaces such as the fetal skin, respiratory and digestive system epithelium, and umbilical arteries and vein express D3 in order to protect the fetus from high thyroid hormone levels and to ensure that the thyroid hormones of the fetus are significantly lower than those of the mother or other adults [1,[10][11][12][13]. The mechanism of the placental D3 expression is not well understood.…”

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves’ disease

“…One mechanism is a high activity of the T 4 and T 3 inactivating deiodinase type 3 (DIO3) in the developing placenta and in the entire uterine wall shortly after blastocyte implantation that takes place in gestational week 4 (23,24). The high DIO3 activity leads to a high concentration of the inactive T 4 metabolite reverse T 3 in maternal blood from very early pregnancy (25,26).…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…In this assay, since the radioactive substrates are labeled in the outer-ring only, the iodide generated cannot be detected, and thus quantitation of the reaction necessitates the separation of the T 2 product from the substrate T 3 by HPLC or descending paper chromatography. Since the T 2 generated is also a good substrate for D3, it is important to dilute the enzyme preparation such that the percent deiodination is relatively low (<20%) and T 2 is the only detectable compound produced (147,(150)(151)(152).…”