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Protein Kinase-C in the Human Fetal Adrenal Gland^*

The Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Departments of Obstetrics and Gynecology and Biochemistry, University of Texas Southwestern Medical Center Dallas, Texas 75235-9032
INSERM U244, Centre D’Etudes Nucleaires de Grenoble 85X 38041 Grenoble, France

Address all correspondence and requests for reprints to: Bruce R. Carr, M.D., Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032.

The fetal zone (FZ) of the human fetal adrenal gland undergoes rapid growth and exhibits a high rate of steroidogenesis throughout fetal life. In addition to cAMP-dependent processes regulating steroidogenesis and possibly growth of the FZ, evidence is accumulating that cAMP-independent mechanisms are also involved. The purpose of this study was to determine if the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent stimulator of protein kinase-C activity, stimulates steroidogenesis in FZ cells and to characterize protein kinase-C activity in FZ, neocortex zone, and anencephalic adrenal tissues. Adrenal glands were obtained from first and second trimester abortions and two anencephalic fetuses. The FZ was dissected from the neocortex. In some experiments, dispersed FZ cells were incubated in the presence and absence of ACTH and TPA for 3 h. TPA and ACTH stimulated steroidogenesis 2- and 5-fold, respectively. In other experiments, the separated zones and anencephalic adrenal tissues were homogenized, and the homogenates were subjected to DEAE-cellulose column chromatography. A single peak with phospholipid- and calciumdependent activity was found. Subcellular distribution studies demonstrated greatest activity in the cytosolic fraction. The specific activity of protein kinase-C was significantly greater in FZ than neocortex zone, whether expressed per mg protein or per µg DNA content. The activity in anencephalic tissue was low. In addition, protein kinase-C (80,000-dalton molecular size protein) was detected in adrenal tissues after electrophoresis and immunoblotting using an antibody directed against protein kinase-C. Greater amounts of protein kinase-C were detected in FZ tissue than in NC or anencephalic adrenal tissue. These results indicate that the lower activities of protein kinase-C in neocortex and anencephalic adrenal tissues were due to low amounts of enzyme rather than inactive enzyme. In summary, TPA-stimulated steroidogenesis in fetal zone cells and fetal zone cells contained greater activity and a greater amount of protein kinase-C than neocortex cells. Minimal activity and enzyme protein were found in anencephalic tissues. These results suggest that cAMP-independent mechanisms may play a role in fetal adrenal steroidogenesis.

^* This work was supported in part by NIH Grants HD-17814 and HD-11149.

Received February 16, 1988.

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