Effects of antenatal glucocorticoids on cerebral protein synthesis in the preterm ovine fetus.
OBJECTIVE
Although antenatal glucocorticoids have well-known benefits for infants who are born preterm by the enhancement of pulmonary maturation, adverse effects on brain growth and development have been reported in several animal-based studies. We have used the chronically catheterized ovine fetus to determine the effects of synthetic glucocorticoids that are administered at doses used clinically on cerebral protein synthesis during early brain development using [13C]-leucine tracer method.


METHODS
Chronically instrumented pregnant sheep at 0.85 gestation received 2 intramuscular injections of betamethasone at 170 microg/kg maternal weight or saline 24 hours apart together with a continuous infusion of L-[1-(13)C]-leucine to the fetus on the second day of experimentation. Measurements were obtained for fetal plasma leucine enrichment at steady-state and brain tissue intracellular free and protein-bound leucine enrichment at necropsy, followed by the determination of cerebral protein fractional synthetic rates (FSRs). A coefficient of variation was determined for plasma and tissue enrichment measurements to assess the inherent methodologic variance with the use of [13C]-leucine tracer technology.


RESULTS
The cerebral protein FSR averaged approximately 112% per day and approximately 35% per day when the intracellular free and plasma enrichment values were used for the precursor pool measurements, respectively, providing for maximal and minimal FSR values. There were no differences between cortical and cerebellar tissues nor between the saline control and the betamethasone animal groups. The coefficient of variation for the plasma-enrichment values averaged approximately 2%; the coefficient of variation for the tissue enrichment values averaged approximately 10%, with an inverse relationship between the [13C]-leucine enrichment values and the coefficient of variation values.


CONCLUSIONS
Although cerebral FSR values for the preterm ovine fetus are high and indicate high rates of protein synthesis and degradation, we found no evidence that these are altered by betamethasone as used clinically and thereby do not account for the reported structural alterations in the brain after a single-course of antenatal glucocorticoids.
McCallum
Jeremy
J
Department of Obstetrics and Gynecology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Smith
Norman
N
MacLachlan
James N
JN
Coksaygan
Turhan
T
Schwab
Matthias
M
Nathanielsz
Peter
P
Richardson
Bryan S
BS
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001783:Blood Flow Velocity; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D007273:Injections, Intramuscular; D008098:Litter Size; D018811:Maternal Exposure; D008565:Membrane Proteins / Q000096:biosynthesis*; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000502:physiology*; D011897:Random Allocation; D012016:Reference Values; D034561:Sheep, Domestic
D005938:Glucocorticoids; D008565:Membrane Proteins; D001623:Betamethasone