Synthesis and Metabolism of 16α‐Hydroxy‐Steroids and Corticosteroids in Fetuses and Neonates

Abstract

This study involved the biosynthesis and metabolism of a series of 16α-hydroxy-steroids and gluco- and mineralocorticoids in the fetus and their concentrations in materno-fetal plasma and amniotic fluid. In the biosynthesis of 16α-hydroxy-steroids, 17α-hydroxylase and C17–20-lyase in the adrenals and 16α-hydroxylase in the liver which are distributed in the microsomal fractions, extremely high activities are observed in 16–20 week fetuses. High sulfokinase activity is also found in the 105,000xg supernatant fraction and the activity in decreasing order is adrenal, liver and small intestine. These enzyme activities are affected by some steroids present in the umbilical plasma. In the biosynthesis of gluco- and mineralocorticoids, 17α-, 21-hydroxylase are distributed in the extramitochondrial fraction of the definitive adrenal cortex while 11β-, 18-hydroxylase and 18-dehydrogenase are in the mitochondrial fraction. All of these enzymes show high activities relatively early in gestation and angiotensin-II shows a selective stimulation for 11β-, 18-hydroxylase and potassium together with ACTH for 18-dehydrogenase. All of the 16α-hydroxy-steroids are consistently higher in the fetal plasma than in maternal plasma and show a 2 to 4 fold increase during the 3rd trimester of gestation. All of corticosteroids assayed are also higher in the fetal plasma and increase during this period. It is well established that a portion of cortisol undergoes sulfate conjugation or conversion to tetrahydro-derivative and that aldosterone is largely converted to 3α' 5β-tetrahydro-aldosterone and a portion undergoes glucosiduronation. Thus, in the fetus, some trophic hormones and endogenous steroids become active in the control of 16α-hydroxy-steroid and corticosteroid biosynthesis and metabolism. In conjunction, the presence of protein bound, unbound fractions as well as sulfate or glucuronide conjugated, unconjugated fractions in the blood tends to maintain an equilibrium and control over these systems.