Relationship between glucose and 20 alpha-hydroxysteroid dehydrogenase in fetal sheep erythrocytes

We have examined whether glucose supply to fetal sheep erythrocytes limits the rate of 20 alpha-reduction of progesterone in blood and as such is associated with the progressive loss of 20 alpha-hydroxysteroid dehydrogenase activity which has been observed from 30 days before term. Enzyme activity in erythrocytes depleted of glucose by washing was regained in the presence of at least 0.167 mmol glucose/1. The cofactor NADPH was necessary to support the reaction in lysed cells. Addition of glucose to whole blood diluted 20-fold for assay of 20 alpha-hydroxysteroid dehydrogenase did not increase the rate of reaction. Infusion of dextrose to increase fetal plasma glucose concentrations had no effect on 20 alpha-hydroxysteroid dehydrogenase activity. Over the period from 114 to 137 days of gestation, both dextrose- and saline-infused fetuses showed a decline in enzyme activity from a combined mean of 1.45 +/- 0.21 (S.E.M.) to a mean of 0.78 +/- 0.18 mumol/ml erythrocytes per h. Fetal leucocytes did not contribute significantly to the activity of 20 alpha-hydroxysteroid dehydrogenase in whole blood. The rate of 20 alpha-reduction of progesterone in the blood of eight fetuses with indwelling carotid catheters declined from 2.31 +/- 0.09 mumol/ml erythrocytes per h at 90-95 days of gestation to 0.73 +/- 0.04 mumol/ml per h at 141-145 days. However, a consistent decline was only observed after 116-120 days. The apparent equilibrium position for progesterone reduction to 20 alpha-dihydroprogesterone varied between 83.9 +/- 1.8 and 65.7 +/- 4.2%.(ABSTRACT TRUNCATED AT 250 WORDS)