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Deoxycorticosterone Biosynthesis from Progesterone in Kidney Tissue of the Human Fetus^*

C. A. WINKEL, M. L. CASEY, E. R. SIMPSON and P. C. MACDONALD

Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Departments of Obstetrics-Gynecology and Biochemistry, University of Texas Southwestern Medical School Dallas, Texas 75235

Address all correspondence and requests for reprints to: Paul C. MacDonald, M.D., Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, Texas 75235.

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 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]D0C formatio from [³H]progesterone (1 µM) proceeded in a linear fashion for 3 h, and the rate of formation of [³H]DOC from [³H]progesterone (1 µM) was linear with a microsomal protein concentration between 0.026–0.512 mg x ml^–1. The value computed for the apparent Kn, of steroid 21-hydroxylase in fetal kidney for progesterone was 0.146 µM. We conclude that the human fetal kidney may be an important site of DOC formation as well as a site of DOC action.

^* This work was supported in part by USPHS Grant 5-P50-HD- 11149. The views expressed in this report are strictly those of the authors and do not necessarily represent those of the U.S. Army.

Lt. Col., Medical Corps, United States Army.

Postdoctoral Fellow supported in part by USPHS Training Grant 1-T32-HD-07190.

Received November 13, 1980.

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