- Accepted Preprint first posted online on 6 January 2011
Thyroid hormones and fetal neurological development
- 1School of Medicine, The University of Queensland, Herston, 4006 Brisbane, Queensland, Australia
2Conjoint Endocrine Laboratory, Queensland Institute of Medical Research, Bancroft Centre, Royal Brisbane and Women's Hospital, 300 Herston Road, Herston, 4029 Brisbane, Queensland, Australia
3Disciplines of Medicine, Obstetrics and Gynaecology, The University of Queensland, Herston, 4006 Brisbane, Queensland, Australia
- (Correspondence should be addressed to J Patel at Conjoint Endocrine Laboratory, Queensland Institute of Medical Research, Bancroft Centre, Royal Brisbane and Women's Hospital; Email: jatin.patel{at}qimr.edu.au)
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 (T4) 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. T4 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.
- Received in final form 21 December 2010
- Accepted 6 January 2011
- © 2011 Society for Endocrinology