title: Thyroid hormones and fetal neurological development.
abstract: The development of fetal thyroid function is dependent on the embryogenesis, differentiation, and maturation of the thyroid gland. This is coupled with evolution of the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism, resulting in the regulation of thyroid hormone action, production, and secretion. Throughout gestation there is a steady supply of maternal thyroxine (T(4)) which has been observed in embryonic circulation as early as 4 weeks post-implantation. This is essential for normal early fetal neurogenesis. Triiodothyronine concentrations remain very low during gestation due to metabolism via placental and fetal deiodinase type 3. T(4) concentrations are highly regulated to maintain low concentrations, essential for protecting the fetus and reaching key neurological sites such as the cerebral cortex at specific developmental stages. There are many known cell membrane thyroid hormone transporters in fetal brain that play an essential role in regulating thyroid hormone concentrations in key structures. They also provide the route for intracellular thyroid hormone interaction with associated thyroid hormone receptors, which activate their action. There is a growing body of experimental evidence from rats and humans to suggest that even mild maternal hypothyroxinemia may lead to abnormalities in fetal neurological development. Our review will focus on the ontogeny of thyroid hormone in fetal development, with a focus on cell membrane transporters and TR action in the brain.
authors.affiliation: School of Medicine, The University of Queensland, Herston, 4006 Brisbane, Queensland, Australia. jatin.patel@qimr.edu.au
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Landers
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: R H
authors.initials: RH
authors.lastname: Mortimer
authors.forename: K
authors.initials: K
authors.lastname: Richard
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D013963:Thyroid Hormones