Transport of thyroid hormones to target tissues.
Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively high incidence of neurological disorders in the offspring. The previous assumption that the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous suggestion that iodine per se has an essential role in brain development. Furthermore, the observed factorial rise in thyroxine-binding globulin (TBG) in pregnancy has often been misinterpreted as preventing thyroid hormone loss to either the fetal compartment or excretory systems. However, physiochemical analysis of the role of specific binding proteins in hormone delivery, combined with epidemiological evidence and evolutionary considerations has led us to postulate that a) maternal thyroxine (T4) is transported to the fetus, and is of crucial importance in early fetal development, and b) 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. Placental transfer of maternal T4 in a variety of mammalian species (including humans) is now well established. Further experimental studies in rats have shown that perturbation of the intrauterine thyroid hormone environment during critical phases of brain development results in a spectrum of biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx) rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT TRUNCATED AT 250 WORDS)
Ekins
R P
RP
Division of Molecular Endocrinology, University College London Medical School, United Kingdom.
Sinha
A K
AK
Pickard
M R
MR
Evans
I M
IM
al Yatama
F
F
D000818:Animals; D001921:Brain / Q000196:embryology; D002352:Carrier Proteins / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D005325:Fetal Organ Maturity / Q000502:physiology; D006043:Goiter, Endemic / Q000503:physiopathology*; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D013961:Thyroid Gland / Q000196:embryology; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000502:physiology; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D013974:Thyroxine; D013975:Thyroxine-Binding Proteins; D000097810:Thyroid Hormone-Binding Proteins