Maternal hypothyroxinemia and brain development: I. A hypothetical control system governing fetal exposure to maternal thyroid hormones.
Maternal hypothyroxinemia consequent on endemic iodine deficiency is associated with an increased incidence of neurological disorders in the offspring. Such correlations were originally postulated as reflecting direct effects of elemental iodine on fetal brain development during early pregnancy, it being generally believed that maternal thyroid hormones do not cross the placenta in significant amount in consequence of the presence of elevated concentrations of TBG in maternal blood. However TBG possesses the capacity to enhance T4 transport to particular target organs during pregnancy. This realization led us to hypothesize a) that maternal T4 is transported to the fetus, and is of crucial importance to early fetal development, and b) that TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Subsequent studies in rats demonstrated that maternal T4 traverses the placenta in significant amounts prior to the development of the fetal thyroid. Other studies have led us to suggest that one or more isoforms of HCG may be implicated in a feed-back system interacting with the hypothalamic/pituitary system governing maternal thyroid hormone secretion. Though our experimental work has primarily focused on the effects of thyroid hormones on the fetal brain, we believe it to be likely that fetal exposure to maternal hormones is under placental control, and that other components of this putative system are worthy of study.
Sinha
A K
AK
Department of Molecular Endocrinology, University College and Middlesex School of Medicine, London, United Kingdom.
Pickard
M R
MR
Ekins
R P
RP
D000818:Animals; D001921:Brain / Q000196:embryology*; D006063:Chorionic Gonadotropin / Q000502:physiology; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D011247:Pregnancy; D013974:Thyroxine / Q000097:blood*; D013975:Thyroxine-Binding Proteins / Q000502:physiology
D006063:Chorionic Gonadotropin; D013975:Thyroxine-Binding Proteins; D013974:Thyroxine