Ring A Reduction of Cortisol by Hypertensive Rat Liverin Vitro

Abstract

To further elucidate our previous findings that male rats with renal hypertension have a greater than normal capacity for in vitro reduction of steroid ring A by liver whole ho- mogenate, the 2 A 4 -reducing enzyme systems in- volved have been fractionated by differential centrifugation. Enzyme activities were deter- mined in both normal and hypertensive male rats and the results were compared with normo- tensive female rats. The enzyme responsible for A 4 -5/3-hydrogenation of cortisol found in the liver supernatant (105,000 Xg) revealed no statisti- cally significant differences between the normal and hypertensive male rats. On the other hand, the activity of the A 4 -5«-hydrogenase in the mi- crosomal fraction from livers of hypertensive rats was significantly higher (5-fold) than in normal male rats (p<0.01). Comparison of the ring A reducing ability of normal female, normal male and hypertensive male rat livers revealed that normal female rat liver homogenates (10,000 Xg supernatant) have 2.5 times as much ring A reductase activity as male rat livers, and that this increase in rate is due to greater microsomal A 4 -5a-hydrogenase activity, confirming earlier re- ports in this respect; furthermore, the pattern in hypertensive male rat is quite similar to normal female rat. On the basis of these studies, we would postulate that high blood pressure, or its causative factors, in some way affects the enzy- matic activity involved in the metabolic trans- formation of corticosteroids by the liver. (Endo- crinology 88: 1071, 1971)