title: Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in gestational diabetes?
abstract: Synthesis of thyroid hormones, thyroxine (T4) and tri-iodothyronine (T3), in the human fetus starts from 17 to 19th weeks of gestation. Despite the majority of normal pregnant women reaching adequate levels of circulating thyroid hormones, in some cases, women with normal pregnancies have low level of free T4 during first trimester of pregnancy, suggesting that T4 action may be compromised in those women and their fetuses. In addition, pathological low levels of thyroid hormones are detected in isolated maternal hypothyroxemia (IMH) and clinical hypothyroidism. Nevertheless, human placenta regulates T3/T4 concentration in the fetal circulation by modulating the expression and activity of both thyroid hormone transporters (THT) and deiodinases. Then, placenta can control the availability of T3/T4 in the feto-placental circulation, and therefore may generate an adaptive response in cases where the mother courses with low levels of T4. In addition, T3/T4 might control vascular response in the placenta, in particularly endothelial cells may induce the synthesis and release of vasodilators such as nitric oxide (NO) or vasoconstrictors such as endothelin-1 mediated by these hormones. On the other hand, low levels of T4 have been associated with increase in gestational diabetes (GD) markers. Since GD is associated with impaired placental vascular function characterized by increased NO synthesis in placental arteries and veins, as well as elevated placental angiogenesis, it is unknown whether reduced T4 level at the maternal circulation could result in an altered placental endothelial function during GD. In this review, we analyze available information regarding thyroid hormones and endothelial dysfunction in GD; and propose that low maternal levels of T4 observed in GD may be compensated by increased placental availability of T3/T4 via elevation in the activity of THT and/or reduction in deiodinases in the feto-placental circulation.
authors.affiliation: Group of Research and Innovation in Vascular Health, Facultad de Ciencias de la Salud, Universidad San Sebastian Concepción, Chile ; Facultad de Ciencias de la Salud, Universidad San Sebastián Concepción, Chile.
authors.forename: Enrique
authors.initials: E
authors.lastname: Guzmán-Gutiérrez
authors.affiliation: Facultad de Ciencias de la Salud, Universidad San Sebastián Concepción, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Veas
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.affiliation: Group of Research and Innovation in Vascular Health, Facultad de Ciencias de la Salud, Universidad San Sebastian Concepción, Chile ; Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis, Department of Basic Sciences, University of Bío-Bío Chillán, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Escudero
authors.affiliation: Cellular and Molecular Physiology Laboratory, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile Santiago, Chile ; University of Queensland Centre for Clinical Research, Faculty of Medicine and Biomedical Sciences, University of Queensland Herston, QL, Australia.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
keywords: endothelial dysfunction; gestational diabetes; pregnancy; thyroxine