Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency.
OBJECTIVE
Allopregnanolone suppresses central nervous system activity and has neuroprotective actions in hypoxia-induced brain injury. In pregnant sheep allopregnanolone concentrations are high during fetal life and decline rapidly after birth. We investigated brain allopregnanolone concentrations of fetal and postnatal rats derived from normal and growth restricted pregnancies.


METHODS
Bilateral uterine vessel ligation (or sham) was performed at gestation day 18 to induce uteroplacental insufficiency in WKY rats (n = 7-8 per group). Brain allopregnanolone was measured by radioimmunoassay at 2 study ages, gestation day 20 (n = 6 per group) and postnatal day 6 (n = 6-8 per group), from control and growth-restricted pups.


RESULTS
Fetal brain allopregnanolone concentrations were higher in growth-restricted fetuses compared to control (p < 0.05). Allopregnanolone concentrations decreased at birth with a greater decline in growth restriction (p < 0.05). Postnatal day 6 brain allopregnanolone concentrations were lower in growth restriction (p < 0.05).


CONCLUSIONS
Growth restriction is a potent stimulus for neurosteroid synthesis in the fetal brain in late pregnancy. The low concentrations of allopregnanolone in the growth-restricted postnatal brain suggest a delay in the capacity of the adrenal gland or brain to synthesize pregnane steroids or their precursors and may render the postnatal brain vulnerable to hypoxia-induced injury.
Department of Physiology, The University of Melbourne, Melbourne, Vic., Australia. westcott@unimelb.edu.au
Kerryn T
KT
Westcott
Jonathan J
JJ
Hirst
Isabella
I
Ciurej
David W
DW
Walker
Mary E
ME
Wlodek
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism; D008026:Ligation; D021041:Placental Circulation / Q000502:physiology; D010927:Placental Insufficiency / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011280:Pregnanolone / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
D011280:Pregnanolone