Maternal Thyroid Hormone Action during Embryo-Fetal Development

Tetraiodothyronine (T4) is secreted by the thyroid gland as a prohormone which is converted in the tissues to triiodothyronine (T3), the active hormone that binds to nuclear receptors and initiates thyroid hormone (TH) action. Maternal TH is necessary for differentiation, growth and metabolism in mammals as well as in lower organisms. The biological action of TH can be mediated by TH receptors (TRs) binding to TH-responsive elements (TREs) in the regions of target genes which regulate gene transcription by chromatin remodeling during brain development. Hormonal changes and metabolic demands during pregnancy result in alterations in the biochemical parameters of thyroid function. The main events occurring during pregnancy are: (i) a marked increase in serum thyroxine-binding globulin levels; (ii) a marginal decrease in free thyroid hormone concentrations; (iii) a frequent trend toward a slight rise in basal thyrotropin (TSH) values between the first trimester and term; (iv) a transient stimulation of the maternal thyroid gland by elevated levels of human chorionic gonadotropin (hCG), resulting in a rise in free TH and a decrease in serum TSH concentrations during the first trimester; and (v) altered peripheral metabolism of maternal TH. The changes that occur in T4 and T3 concentrations during pregnancy might generate clinical challenges during brain development. If so, T4 replacement would be needed in those women with hypothyroidism. We will review the most recent advances in: (i) molecular mechanisms of TH during embryo-fetal brain development, and (ii) morphological changes in the brain due to maternal hypothyroidism.