Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta.
The influence of maternal hypothyroxinemia on the expression of the glucose transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investigated. Fetal growth was retarded in hypothyroxinemic pregnancies, but only before the onset of fetal thyroid hormone synthesis. Placental weights were normal, but placental total protein concentration was reduced at 19 days gestation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in placental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum glucose levels were reduced at 16 dg. In fetal brain, the concentration of microsomal protein was deficient at 16 dg and the abundance of parenchymal forms of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hybridization analysis demonstrated normal GLUT1 mRNA levels in placenta and fetal brain. In conclusion, maternal hypothyroxinemia results in fetal growth retardation and impaired brain development before the onset of fetal thyroid function. Glucose uptake in fetal brain parenchyma may be compromised directly, due to deficient GLUT1 expression in this tissue, and indirectly, as a result of reduced placental GLUT1 expression. Though corrected by the onset of fetal thyroid hormone synthesis, these deficits are present during the critical period of neuroblast proliferation and may contribute to long term changes in brain development and function seen in this model and in the progeny of hypothyroxinemic women.
Pickard
M R
MR
Division of Molecular Endocrinology, University College London Medical School, Mortimer Street, London W1N 8AA, UK.
Sinha
A K
AK
Ogilvie
L M
LM
Leonard
A J
AJ
Edwards
P R
PR
Ekins
R P
RP
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D015870:Gene Expression; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D014284:Triiodothyronine; D013974:Thyroxine