Angiotensin II regulates cytochrome P-450 steroid hydroxylase enzyme expression in human adrenal glomerulosa cells.
We have examined the regulation of cytochrome P-450 side chain cleavage enzyme (P-450SCC) and P-45011 beta (18) hydroxylase (P-450(11) beta) enzyme expression by angiotensin II (AII), the major regulator of aldosterone biosynthesis, in cultured human adrenal glomerulosa cells. We also examined the effect of lipoxygenase products of arachidonic acid on the expression of these enzymes since it has been previously shown that the 12-lipoxygenase pathway plays a key role in AII-induced aldosterone synthesis in rat and human adrenal glomerulosa cells. AII (10(-7) mol/L) induced a 3-fold stimulation of P-450SCC and over a 2-fold increase in P-450(11) beta protein expression. The 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) caused a 2-fold increase in P-450(11) beta levels without altering P-450SCC levels. These results show for the first time that AII can directly increase the levels of P-450SCC and P-450(11) beta enzymes in glomerulosa cells. The results also suggest that 12-HETE may mediate long term effects of AII action by stimulating P-450(11) beta levels.
Natarajan
R
R
Department of Diabetes, Endocrinology, and Metabolism, City of Hope Medical Center, Duarte, California 91010.
Yang
H
H
Hall
P F
PF
Nadler
J
J
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D015153:Blotting, Western; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000201:enzymology*
D006893:Hydroxyeicosatetraenoic Acids; D000804:Angiotensin II; D000450:Aldosterone; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme