Mr. Pickard et al., Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta, J ENDOCR, 163(3), 1999, pp. 385-394
The influence of maternal hypothyroxinemia on the expression of the glucose
transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investi
gated. 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 g
estation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in pl
acental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum gluco
se levels were reduced at 16 dg. In fetal brain, the concentration of micro
somal protein was deficient at 16 dg and the abundance of parenchymal forms
of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hyb
ridization analysis demonstrated normal GLUT1 mRNA levels in placenta and f
etal brain.
In conclusion, maternal hypothyroxinemia results in fetal growth retardatio
n 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 fet
al thyroid hormone synthesis, these deficits are present during the critica
l period of neuroblast proliferation and may contribute to long term change
s in brain development and function seen In this model and in the progeny o
f hypothyroxinemic women.