Alterations in maternal and fetal prostaglandin dehydrogenase as a result of maternal ethanol consumption.
Various lines of research have suggested that ethanol consumption may alter prostaglandin-related physiology. Our laboratory has reported that chronic exposure to high doses of ethanol lowers the ability of kidney and lung homogenates from rats to catabolize prostaglandin E2 and F2 alpha via 15-prostagladin dehydrogenase (PGDH). Because of the apparently unique role played by prostaglandins in conception, growth and development of the fetus and parturition, we have attempted to determine if the alterations observed in male rats also occur in females and if any alterations in fetal metabolism result from maternal ethanol exposure. Further, we have measured the influence of ethanol administration on renal clearance of the 15-keto metabolite of PGF2 alpha in an attempt to determine the in vivo significance of the enzyme inhibition observed in vitro. Initial results indicate the following. 1) Female Holtzman rats doses at 2.0, 5.0 and 7.0 mg ethanol/kg during the first, second, and third trimesters of pregnancy, respectively, showed losses in renal PGDH activity similar to those found in males (1.52 versus 1.05 picomole/min/mg, p < 0.001 by matched t-test). 2) Placental tissue (amnion) isolated from these same animals on day 21 of the pregnancies also showed a significant decrease in PGDH activity (14.79 versus 11.77 picomoles/min/mg, p < 0.01). 3) Kidney homogenates from fetuses delivered on day 21 of the pregnancies showed a significant increase in PGDH relative to pair-dosed controls (16.77 versus 12.65 picomoles/min/mg, p < 0.01). 4) In a separate experiment, urinary clearance of PGF2 alpha metabolite was inhibited in a dose related manner up to a level of 6 gm/kg.
D011452:15-Oxoprostaglandin 13-Reductase / Q000037:antagonists & inhibitors*; D000437:Alcoholism / Q000201:enzymology*; D000650:Amnion / Q000201:enzymology; D000818:Animals; D005260:Female; D005333:Fetus / Q000201:enzymology*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology*; D051381:Rats
D010088:Oxidoreductases; D011452:15-Oxoprostaglandin 13-Reductase