Acute and chronic ethanol treatment in vivo increases malate-aspartate shuttle capacity in perfused rat liver.

The effects of acute and chronic treatment with ethanol on transport of reducing equivalents into mitochondria via the malate-aspartate shuttle were studied in perfused rat liver. The shuttle capacity was estimated from the decrease in rates of glucose production from the reduced substrate sorbitol caused by an increase in the NADH/NAD+ ratio in the cytosol due to metabolism of ethanol. The greater the capacity of the malate-aspartate shuttle, the smaller the inhibition of glucose synthesis by ethanol. Glucose synthesis was decreased about 2-fold less in livers from fasted rats treated acutely 2.5 h earlier with ethanol than in untreated controls. Chronic treatment with ethanol for 3-5 weeks prevented completely the decrease in glucose synthesis from sorbitol due to ethanol oxidation. Rates of ethanol uptake were elevated significantly from 69 +/- 7 mumols/g/h in livers from control rats up to 92 +/- 7 mumols/g/h in livers from SIAM rats. Similarly, rates of ethanol uptake were stimulated by chronic ethanol treatment from 71 +/- 6 to 222 +/- 15 mumols/g/h; this increase was largely sensitive to aminooxyacetate. Taken together, these data indicate that flux of reducing equivalents over the malate-aspartate shuttle is increased by both acute and chronic treatment with ethanol and that movement of reducing equivalents from the cytosol into the mitochondria via the malate-aspartate shuttle is an important rate determinant in hepatic ethanol oxidation

The balance between fetal oxytocin and placental leucine aminopeptidase (P-LAP) controls human uterine contraction around labor onset

A fetal pituitary hormone, oxytocin which causes uterine contractions, increases throughout gestation, and its increase reaches 10-fold from week 32 afterward. Oxytocin is, on the other hand, degraded by placental leucine aminopeptidase (P-LAP) which exists in both terminal villi and maternal blood. Maternal blood P-LAP increases with advancing gestation under the control of non-genomic effects of progesterone, which is also produced from the placenta. Progesterone is converted to estrogen by CYP17A1 localized in the fetal adrenal gland and placenta at term. The higher oxytocin concentrations in the fetus than in the mother demonstrate not only fetal oxytocin production but also its degradation and/or inhibition of leakage from fetus to mother by P-LAP. Until labor onset, the pregnant uterus is quiescent possibly due to the balance between increasing fetal oxytocin and P-LAP under control of progesterone. A close correlation exists between the feto-placental and maternal units in the placental circulation, although the blood in the two circulations does not necessarily mix. Fetal maturation results in progesterone withdrawal via the CYP17A1 activation accompanied with fetal oxytocin increase. Contribution of fetal oxytocin to labor onset has been acknowledged through the recognition that the effect of fetal oxytocin in the maternal blood is strictly regulated by its degradation by P-LAP under the control of non-genomic effects of progesterone. In all senses, the fetus necessarily takes the initiative in labor onset