Expression of hepatic microsomal cholesterol 7 alpha-hydroxylase activity in lean and obese Zucker rats

The activity of hepatic microsomal cholesterol 7 alpha-hydroxylase was studied in genetically obese and lean Zucker rats. The liver microsomal cholesterol 7 alpha-hydroxylase activity in fatty Zucker rats (fa/fa) is about 50% to 70% lower than that of the lean (Fa/-) rats of the same sex, when animals were sacrificed at the middle of the dark cycle. When rats were sacrificed at the middle of the light cycle, cholesterol 7 alpha-hydroxylase activity was the same as in the dark cycle in obese rats of both sexes, but was 65% lower in lean rats. However, cholesterol 7 alpha-hydroxylase activity was stimulated by the treatment with cholestyramine in both obese and lean rats. Our results suggested that the diurnal regulation of cholesterol 7 alpha-hydroxylase activity is lost in obese rats but was present under cholestyramine treatment in the genetically obese strain of rats.     

The role of cytochrome P-450 in cholesterol biogenesis and catabolism

1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [(14)C]acetate or [(14)C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7alpha-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7alpha-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.     

Regulation of cholesterol 7 alpha-hydroxylase by hepatic 7 alpha-hydroxylated bile acid flux and newly synthesized cholesterol supply

We measured hepatic cholesterol 7 alpha-hydroxylase activity, mass, and catalytic efficiency (activity/unit mass) in bile fistula rats infused intraduodenally with taurocholate and its 7 beta-hydroxy epimer, tauroursocholate, with or without mevalonolactone to supply newly synthesized cholesterol. Enzyme activity was measured by an isotope incorporation assay and enzyme mass by densitometric scanning of immunoblots using rabbit anti-rat liver cholesterol 7 alpha-hydroxylase antisera. Cholesterol 7 alpha-hydroxylase activity increased 6-fold, enzyme mass 34%, and catalytic efficiency 5-fold after interruption of the enterohepatic circulation for 48 h. When taurocholate was infused to the bile acid-depleted animals at a rate equivalent to the hepatic bile acid flux (27 mumol/100-g rat/h), cholesterol 7 alpha-hydroxylase activity and enzyme mass declined 60 and 61%, respectively. Tauroursocholate did not significantly decrease cholesterol 7 alpha-hydroxylase activity, mass and catalytic efficiency. The administration of mevalonolactone, which is converted to cholesterol, modestly increased cholesterol 7 alpha-hydroxylase activity and enzyme mass in the bile acid-depleted rats. However, when taurocholate was infused together with mevalonolactone, cholesterol 7 alpha-hydroxylase activity and catalytic efficiency were markedly depressed while enzyme mass did not change as compared with bile acid-depleted rats. These results show that (a) hepatic bile acid depletion increases bile acid synthesis mainly by activating cholesterol 7 alpha-hydroxylase with only a small rise in enzyme mass, (b) replacement with taurocholate for 24 h decreases both cholesterol 7 alpha-hydroxylase activity and mass proportionally, (c) when cholesterol is available (mevalonolactone supplementation), the infusion of taurocholate results in the formation of a catalytically less active cholesterol 7 alpha-hydroxylase, and (d) tauroursocholate, the 7 beta-hydroxy epimer of taurocholate, does not inhibit cholesterol 7 alpha-hydroxylase. Thus, bile acid synthesis is modulated by the catalytic efficiency and mass of cholesterol 7 alpha-hydroxylase. The enterohepatic flux of 7 alpha-hydroxylated bile acids and the formation of hepatic cholesterol apparently control cholesterol 7 alpha-hydroxylase by different mechanisms.     

Regulatory effects of sterols and bile acids on hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7alpha-hydroxylase in the rat

Specific activities of the hepatic microsomal enzymes 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase and cholesterol 7alpha-hydroxylase were studied in rats fed sterols and bile acids. The administration of bile acids (taurocholate, taurodeoxycholate, taurochenodeoxycholate) at a level of 1% of the diet for 1 wk reduced the activity of HMG CoA reductase. Taurocholate and taurodeoxycholate, but not taurochenodeoxycholate, inhibited cholesterol 7alpha-hydroxylase. Dietary sitosterol produced increases in the specific activity of HMG CoA reductase (3.6-fold) and cholesterol 7alpha-hydroxylase (1.4-fold), and biliary cholesterol concentrations in this group more than doubled. Compared with controls fed the stock diet, the simultaneous administration of sitosterol and taurochenodeoxycholate resulted in a 60% decrease of HMG CoA reductase activity and no change in cholesterol 7alpha-hydroxylase activity or biliary cholesterol concentration. Rats fed sitosterol plus taurocholate had nearly normal HMG CoA reductase activity, but cholesterol 7alpha-hydroxylase was inhibited and biliary cholesterol remained high. Bile acid secretion rates and biliary bile acid composition were similar in controls and sterol-fed animals. In all groups receiving bile acids, biliary secretion of bile acids was nearly doubled and bile acid composition was shifted in the direction of the administered bile acid. It is concluded that the composition of the bile acid pool influences the hepatic concentrations of the rate-controlling enzymes of bile acid synthesis.     

Sterol balance studies in the rat. Effects of dietary cholesterol and beta-sitosterol on sterol balance and rate-limiting enzymes of sterol metabolism.

Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed diets containing beta-sitosterol (0.8%) and cholesterol (1.2%). The activities of the rate-limiting enzymes of cholesterol synthesis (beta-hydroxy-beta-methylglutaryl-CoA reductase, EC 1.1.1.34) and bile acid synthesis (cholesterol 7 alpha-hydroxylase) were determined in the same animals. Cholesterol feeding increased cholesterol absorption from 1.2 to 70 mg/day. The increased absorption was compensated for by inhibition of hepatic cholesterol synthesis, enhanced conversion of cholesterol to bile acids (from 13.7 to 27.3 mg/day) and a slight increase in the excretion of endogenous neutral steroids (from 7.7 to 11.2 mg/day). Despite the adaptation there was accumulation of cholesterol in the liver (from 2.2 to 9.2 mg/g). Beta-Sitosterol feeding inhibited cholesterol absorption (calculated absorption was zero). In these rats there was enhanced cholesterol synthesis (from 20.0 to 28.8 mg/day, but no change in the rates of bile acid formation. Measurements of the activities of the rate-limiting enzymes showed fair correlation with cholesterol-bile acid balance. In cholesterol fed animals, beta-hydroxy-beta-methylglutaryl-CoA reductase was inhibited 80% and cholesterol 7 alpha-hydroxylase was enhanced 61%. In beta-sitosterol-fed animals, the reductase was increased 2-fold and cholesterol 7 alpha-hydroxylase was not significantly different from controls.     

Cholesterol 7 alpha-hydroxylase in isolated rat liver cells.

1. The activity of cholesterol 7 alpha-hydroxylase found in the 10000 x g supernatant prepared from isolated rat liver cells was comparable to that found with microsomal fractions from whole liver. 2. The activity of cholesterol 7 alpha-hydroxylase from cells prepared from livers of rats fed the bile salt sequestering agent cholestyramine was 2--3 fold higher than the activity of this enzyme found in cells isolated from animals on a control diet. 3. On incubation of hepatocytes in a suitable medium at 37 degrees C, cholesterol 7 alpha-hydroxylase activity declined to about 50% of its original value after three hours despite the fact that the cells retained a high level of viability over 5--6 h as measured by various sensitive criteria. 4. The decrease in cholesterol 7 alpha-hydroxylase activity was observed whether cholestyramine was included in the diet or excluded from the diet of the animals used as sources of the liver cells. 5. The change in cholesterol 7 alpha-hydroxylase activity seen on incubation of the cells was not affected by including in the incubation medium additional nutrients such as amino acids, the glucocorticoid cortisol, phospholipid dispersions, or sodium taurocholate. 6. Changing the incubation medium in which the cells were suspended at regular intervals during the three-hour experiments failed to prevent this decline in the cholesterol 7 alpha-hydroxylase activity during the incubation of these cells. 7. Although isolated liver cells have been shown to lose glutathione on incubation, addition of physiological levels of this compound did not prevent the decline in cholesterol 7 alpha-hydroxylase activity. 8. Cycloheximide addition to the incubation medium accelerated the decrease in cholesterol 7 alpha-hydroxylase activity. This suggests that some protein synthesis associated with cholesterol 7 alpha-hydroxylase activity occurs during the incubation and inhibition of such protein synthesis accelerated the decrease in this enzyme activity. 9. The cytochrome P-450 content of the 10000 x g supernatant prepared from hepatocytes declined slowly to about 65% of its original value after four hours of incubation at 37 degrees C. This decline in the 10000 x g supernatant cytochrome P-450 content may partly explain the observed loss of cholesterol 7 alpha-hydroxylase activity during incubations in vitro. 10. Isolated hepatocytes rapidly take up radioactively labelled sodium cholate. Subsequent excretion of the radioactivity was also very rapid even in the presence of large amounts of this bile salt in the medium.     

The effect of dimethyl sulfoxide on cholesterol and bile acid metabolism in rats

The effect of DMSO on cholesterol and bile acid metabolism was studied in rats. Male Sprague-Dawley rats were randomly assigned to one of two groups and given either tap water or 2% DMSO (v/v) in tap water to drink for 9 days. Both food (stock rat diet) and water were available ad libitum. Animals in both groups gained weight equally throughout the study. They also had similar liver weights (g/100 g body wt) at the end of the study (control: 5.0 +/- 0.1 (N = 6) vs DMSO: 4.9 +/- 0.1 (N = 6]. The activity of hepatic cholesterol 7 alpha-hydroxylase (pmole/mg/min), the rate-limiting enzyme of bile acid biosynthesis, was significantly (P less than 0.005) reduced in the treated animals (control: 9.7 +/- 1.0 (N = 6) vs DMSO: 4.3 +/- 0.7 (N = 6)). Plasma cholesterol (mg/dl) was significantly (P less than 0.005) elevated in the treated animals (control: 90 +/- 3 (N = 6) vs DMSO: 107 +/- 4 (N = 6)), a finding consistent with the reduced CH-7 alpha hydroxylase activity in this group. DMSO treatment did not affect either microsomal cholesterol content or hepatic glutathione content. Thus, this study has shown that DMSO treatment per se can affect cholesterol and bile acid metabolism. However, the precise mechanisms whereby DMSO exerts the observed effects are not known.     

Regulation of bile acid synthesis via direct effects on the microsomal membrane

Rats treated with ethinylestradiol (5 mg kg-1 day-1 for 5 days) secrete de novo synthesized bile acids at a markedly reduced rate (-57%). Administration of the nonionic detergent Triton WR-1339 to estradiol-treated rats rapidly restored the rate of secretion of de novo synthesized bile acids to control levels. In contrast, when Triton was administered to control rats, the secretion rate of bile acids was unaffected. The reduction in bile acid synthesis displayed by estradiol-treated rats was similar to the 50% decrease in the activity of hepatic microsomal 7 alpha-hydroxylase. The activity of 7 alpha-hydroxylase was also restored to control levels by the administration of Triton to estradiol-treated rats. We examined the possibility that estradiol acts directly on the hepatic microsomes. Adding increasing amounts of estradiol to microsomes obtained from control rats resulted in decreasing activities of 7 alpha-hydroxylase. The inhibition by estradiol of 7 alpha-hydroxylase obtained in vitro occurred with amounts of estradiol that were found to accumulate in the liver via in vivo treatment. Double-reciprocal analysis showed that at and below 50 micrograms of estradiol/0.5 mg of protein uncompetitive inhibition was displayed. Additional experiments showed that adding Triton to microsomes obtained from estradiol-treated rats increased the activity of 7 alpha-hydroxylase to control levels. In contrast, Triton did not increase the activity of 7 alpha-hydroxylase when it was added to control microsomes. These data show for the first time that the estrogenic steroid estradiol acts directly on the microsomes and inhibits both the activity of 7 alpha-hydroxylase and the rate of bile acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of cholesterol 7 alpha-hydroxylase in the liver. Purification of cholesterol 7 alpha-hydroxylase and the immunochemical evidence for the induction of cholesterol 7 alpha-hydroxylase by cholestyramine and circadian rhythm

Two cholesterol 7 alpha-hydroxylase isozymes were purified from liver microsomes of cholestyramine-treated female rats by using anion exchange high performance liquid chromatography. These two cytochrome P-450 isozymes were similar in electrophoretic mobility, immunocross-reactivity, and Vmax but differed in Km for cholesterol, turnover number, and charges. Antibody against the major isozyme was raised in rabbit. This antibody specifically inhibited microsomal cholesterol 7 alpha-hydroxylase activity. Immunoblot of microsomal polypeptides indicated that microsomal cholesterol 7 alpha-hydroxylase enzyme levels were increased in parallel with cholesterol 7 alpha-hydroxylase activity upon the treatment of rats with diet supplemented with cholestyramine. Both cholesterol 7 alpha-hydroxylase activity and enzyme levels were drastically reduced immediately after the removal of cholestyramine from the diet. Cholesterol 7 alpha-hydroxylase activity was also detected in the microsomes of kidney, heart, and lung in about 7-27% of the level found in the liver. 3-Methylcholanthrene treatment induced cholesterol 7 alpha-hydroxylase activity and enzyme level. In contrast, pregnenolone-16 alpha-carbonitrile or dexamethasone treatment greatly depressed enzyme and activity in rats. Cholesterol 7 alpha-hydroxylase enzyme level was 2-3-fold higher in liver microsomes of rats maintained under the reversed light cycle than under the normal light cycle. In genetically obese Zucker rats, cholesterol 7 alpha-hydroxylase activity and enzyme level did not respond to the change in the light cycle, however, were induced to the same levels as in the lean rats by cholestyramine treatment. This study provided the first direct evidence that the bile acid feedback regulation and circadian rhythm of microsomal cholesterol 7 alpha-hydroxylase activity involved the induction of cholesterol 7 alpha-hydroxylase enzyme level.     

Effects of treatment with clofibrate, bezafibrate, and ciprofibrate on the metabolism of cholesterol in rat liver microsomes

The effects of treatment of rats with clofibrate, bezafibrate, and ciprofibrate on the hepatic metabolism of cholesterol were studied in rat liver microsomes. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity, regulating cholesterol biosynthesis, was unaffected by clofibrate and ciprofibrate and slightly decreased (20%) by bezafibrate. Also cholesterol 7 alpha-hydroxylase activity, governing bile acid biosynthesis, was unaffected by clofibrate and was reduced by 25-30% in the two other groups of rats. A major new finding was that all three fibric acid derivatives reduced ACAT (acyl-coenzyme A:cholesterol acyltransferase) activity, catalyzing the esterification of cholesterol, by 50-70%. The hepatic content of free and esterified cholesterol was determined in the bezafibrate-treated rats. The concentration of microsomal cholesteryl ester was about 60% lower in the treated rats compared to the controls whereas the concentration of total cholesterol was unchanged.     

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females.These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.     

Regulation of hydroxylations in biosynthesis of bile acids. Isolation of a protein from rat liver cytosol stimulating reconstituted cholesterol 7 alpha-hydroxylase activity

Modulation of cholesterol 7 alpha-hydroxylase activity was studied in a purified, reconstituted system from rat liver microsomes. Cysteine, dithiothreitol, reduced glutathione, and thioredoxin activated the system whereas glutathione disulfide inactivated it. A protein, which stimulated cholesterol 7 alpha-hydroxylase activity in the presence of glutathione or thioredoxin, was purified to apparent homogeneity from rat liver cytosol. It has a minimum Mr of 25,000. The protein had no effect on 12 alpha-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one or 25-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. The cholesterol 7 alpha-hydroxylase stimulatory protein could not be replaced by the thioltransferase-dependent disulfide-reducing system nor by glutathione S-transferase A, B, or C. Neither ATP and MgCl2 nor sodium fluoride had any effect on the activity of the cholesterol 7 alpha-hydroxylase stimulatory protein. The results show that purified cholesterol 7 alpha-hydroxylase can be regulated by a mechanism involving disulfide bonds in the cytochrome P-450 molecule.     

Development of bile acid metabolism: effect of glucocorticoids on bile acid metabolism in the neonatal rat

The objective of this study was to examine the effect of glucocorticoid treatment in early neonatal life on plasma cholesterol and hepatic cholesterol 7 alpha-hydroxylase (CH-7A), the rate-limiting enzyme of bile acid biosynthesis from cholesterol, measured at weaning (Postnatal Day 20). Neonatal rat pups were injected subcutaneously with 5 micrograms of dexamethasone (DEXA) or vehicle (CON) for 5 days between Postnatal Days 4 and 8. On Postnatal Day 20, the animals were used for various studies. DEXA-treated pups weighed significantly less (P less than 0.001) than controls. Even though DEXA-treated animals had significantly smaller livers (P less than 0.001), microsomal protein per gram of liver was significantly greater (P less than 0.005) in the DEXA-treated animals. CH-7A activity (pmole/mg . min) was significantly lower (P less than 0.005) in the DEXA-treated animals (CON (4) 19.4 +/- 2.8; DEXA (4) 5.0 +/- 1.0). Plasma cholesterol (mg/100 ml) was significantly greater (P less than 0.005) in the DEXA-treated animals (CON (5) 179 +/- 7; DEXA (4) 223 +/- 5), a finding consistent with lower CH-7A activity in this group. Taurocholate absorption by in situ ileal loops in anesthetized rats was significantly greater in the DEXA-treated animals in agreement with the in vitro observations of Little and Lester. The basis for the reduced CH-7A activity in DEXA-treated pups is not known. It may be due in part to a new steady state in the enterohepatic circulation of bile acids resulting from a glucocorticoid-induced enhanced conservation of bile acids.     

Dietary soybean protein moderates the deleterious disturbance of lipid metabolism caused by exogenous oxidized cholesterol in rats.

Effects of dietary protein on oxidized cholesterol-induced disturbance of lipid metabolism were examined in 4 week old male Sprague-Dawley rats, using casein and soybean protein as dietary protein source. The rats were given one of the two proteins in 0. 078% cholesterol (control), 0.25% cholesterol or 0.25% oxidized cholesterol mixture (containing 0.078% cholesterol) diets. Dietary oxidized cholesterol, compared to cholesterol, tended to inhibit hepatic sterol biosynthesis in casein-fed rats, whereas this inhibitory action was slightly moderated by intake of soybean protein. As a result, the hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity was rather higher in the rats fed oxidized cholesterol than in those fed cholesterol in the soybean protein-fed group. The hepatic cholesterol 7alpha-hydroxylase activity tended to be higher in the rats fed oxidized cholesterol than in those fed control diet in the soybean protein-fed group, despite the fact that oxidized cholesterol lowered the hydroxylase activity in the casein-fed group. On the other hand, dietary oxidized cholesterol tended to slightly enhance the hepatic Delta6 desaturase activity in the casein-fed group; however, this observation was not shown in the soybean protein-fed group. Moreover, dietary soybean protein facilitated fecal oxidized cholesterol excretion and simultaneously inhibited the accumulation of oxidized cholesterol in serum and liver. In conclusion, dietary soybean protein alleviated the deleterious actions of exogenous oxidized cholesterol on hepatic cholesterol and linoleic acid metabolism, although these efficacies were not necessarily significant. A great part of these moderations may be exerted by the specific hypocholesterolemic function of soybean protein, such as the stimulation of fecal oxidized cholesterol excretion, the change of hormonal release and modulation of lipoprotein catabolism.     

Complexation of cytochrome P-450 isozymes in hepatic microsomes from SKF 525-A-induced rats

Potassium ferricyanide-elicited reactivation of steroid hydroxylase activities, in hepatic microsomes from SKF 525-A-induced male rats, was used as an indicator of complex formation between individual cytochrome P-450 isozymes and the SKF 525-A metabolite. Induction of male rats with SKF 525-A (50 mg/kg for three days) led to apparent increases in androst-4-ene-3,17-dione 16 beta- and 6 beta-hydroxylation to 6.7- and 3-fold of control activities. Steroid 7 alpha-hydroxylase activity was decreased to 0.8-fold of control and 16 alpha-hydroxylation was unchanged. Ferricyanide-elicited dissociation of the SKF 525-A metabolite-P-450 complex revealed an even greater induction of 16 beta- and 6 beta-hydroxylase activities (to 1.8- and 1.6-fold of activities in the absence of ferricyanide). Androst-4-ene-3,17-dione 16 alpha-hydroxylase activity increased 2-fold after ferricyanide but 7 alpha-hydroxylase activity was unaltered. An antibody directed against the male-specific cytochrome P-450 UT-A decreased androst-4-ene-3,17-dione 16 alpha-hydroxylase activity to 13% of control in hepatic microsomes from untreated rats. In contrast, 16 alpha-hydroxylase activity in microsomes from SKF 525-A-induced rats, before and after dissociation with ferricyanide, was reduced by anti UT-A IgG to 32 and 19% of the respective uninhibited controls. Considered together, these observations strongly suggest that the phenobarbital-inducible cytochrome P-450 isozymes PB-B and PCN-E are present in an inactive complexed state in microsomes from SKF 525-A-induced rat liver. Further, the increased susceptibility of androst-4-ene-3,17-dione 16 alpha-hydroxylase activity to inhibition by an antibody to cytochrome P-450 UT-A, following ferricyanide treatment of microsomes, suggests that this male sexually differentiated enzyme is also complexed after in vivo SKF 525-A dosage. In contrast, the constitutive isozyme cytochrome P-450 UT-F, which is active in steroid 7 alpha-hydroxylation, does not appear to be complexed to any extent in microsomes from SKF 525-A-induced rats.     

Effect of estrogen and progesterone on the hepatic cholesterol 7-alpha-hydroxylase activity in ovariectomized baboons

Cholesterol 7 alpha-hydroxylase activity was measured in livers from ovariectomized baboons fed a high cholesterol high saturated fat diet and maintained in four groups: untreated controls, estrogen (100 micrograms/g per week), progesterone (3 mg/kg per day) and estrogen + progesterone. Estrogen treatment alone increased hepatic 7 alpha-hydroxylase activity by 2.7-fold, whereas progesterone treatment alone did not influence hepatic 7 alpha-hydroxylase activity. The increase in 7 alpha-hydroxylase activity in estrogen + progesterone group was similar to that in the estrogen group.