Abstract

Whereas total P-450 content is more than four times greater in the rat adrenal cortex mitochondria than in microsomes, aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2) activity is more than 60 times higher in adrenal cortex microsomes than in mitochondria. The rat adrenal microsomal hydroxylase activity is strongly inhibited by α-naphthoflavone in vitro; progesterone 21-hydroxylase is not. In rats hypophysectomized for 30 days, aryl hydrocarbon hydroxylase decreases to about 6% of control values, but progesterone 21-hydroxylase falls to about 38% of that in sham-operated control animals. Hypophysectomy causes a striking decrease in an ebectrophoretic band estimated to be about 57,000 daltons. Aryl hydrocarbon hydroxylase specific activity and this electrophoretic band are restored to normal levels in adrenal microsomes of hypophysectomized rats that have received exogenous ACTH treatment. Aryl hydrocarbon hydroxylase in adrenal microsomes is not induced, however, in the hypophysectomized or intact rat by 3-methylcholanthrene or high doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin. These data show that aryl hydrocarbon hydroxybase and progesterone 21-hydroxylase may be associated with different forms of adrenal microsomal P-450. It is of interest that aryl hydrocarbon hydroxylase in the adrenal of the untreated rat is similar (in sensitivity to α-naphthoflavone and in the presumed association with the 57,000-dalton apoprotein subunit on electrophoresis) to polycyclic aromatic compound-induced aryl hydrocarbon hydroxylase and its associated cytochrome P₁-450 in rat liver. The regulation of the adrenal hydroxylase by the large polypeptide hormone ACTH and the lack of inducibility by polycycic aromatic compounds, however, are characteristics distinctly different from those of the P₁-450-associated hepatic enzyme.