Deoxycorticosterone biosynthesis from progesterone in kidney tissue of the human fetus

The levels of deoxycorticosterone (DOC) and DOC sulfate are extraordinarily high in the umbilical cord plasma of human newborns. However, the sources of DOC and DOC sulfate in the human fetus are not defined. Recently, it was shown that plasma progesterone was converted to DOC in extraadrenal tissues in pregnant, nonpregnant, and adrenalectomized women and in men. Thus, DOC formation from plasma progesterone constitutes another example of the formation of a biologically active steroid hormone from a circulating precursor. In addition, the conversion of [3H]progesterone to [3H]DOC in homogenates and microsome-enriched preparations of adult human kidney tissue was demonstrated. To investigate the origin of DOC in the human fetus, we sought 1) to ascertain whether steroid 21-hydroxylase activity was present in human fetal kidney tissue and 2) to establish the kinetics of the reaction catalyzed by this enzyme should it be present in fetal kidney. We employed microsome-enriched preparations of kidney tissue obtained from human abortuses of 9-20 weeks gestation. [3H]DOC formation from [3H]progesterone (1 microM) proceeded in a linear fashion for 3 h. and the rate of formation of [3H]DOC from [3H]progesterone (1 microM) was linear with a microsomal protein concentration between 0.026-0.512 mg X ml-1. The value computed for the apparent Km of steroid 21-hydroxylase in fetal kidney for progesterone was 0.146 microM. We conclude that the human fetal kidney may be an important site of DOC formation as well as a site of DOC action.