RELATIONSHIP OF LOW PROTEIN DIET AND ASCORBIC ACID IN ESTROGEN INACTIVATION BY LIVER

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Abstract
It has been shown that an adequate protein intake is necessary for estrogen inactivation by the liver (13, 14). Since it has been reported that liver glutathione and ascorbic acid are decreased in either low protein or protein free diets (16, 17, 18), this investigation was carried out to determine if ascorbic acid and glutathione are involved in estrogen metabolism in the liver. This was studied by both in vivo and in vitro experiments using Sprague-Dawley female albino rats. In the in vivo experiments adult rats were ovariectomized and implanted with a pellet of estrone according to the method of Burrill and Greene (19). The inactivation of the estrogen was followed by the vaginal smear method. After three weeks of anestrous smears, the animals were placed on an 8% casein diet and within 10 days the animals lost the ability to inactivate the estrogen. Beginning on the first day of the 11th week, glutathione was injected intraperitoneally daily for two weeks, followed by daily injections of ascorbic acid in addition to the glutathione for two more weeks. In a separate experiment ascorbic acid alone was injected for 8 days. The effect of glutathione was sporadic but when ascorbic acid was added, either with glutathione or alone, the animals regained completely the ability to inactivate estrone. In the in vitro studies one group of adult female rats was maintained on the same 8[degree] casein diet used in the in vivo experiments. A second group of rats was maintained on an adequate 21[degree] casein diet in which there was an isocaloric substitution of the added casein for sucrose. After 2 1/2-3 months the rats were sacrificed and the livers removed and sliced. The liver slices were incubated with estrone or estradiol, with and without ascorbic acid, for 1-1 1/2 hours at 37[degree] C. The amount of estrogen inactivation was measured by the bioassay method of Lauson et al. (22). The effect of diphosphopyridine nucleotide, glutathione and liver extract on the inactivation of estrone by liver slices was also studied. The results of the in vitro experiments showed that liver slices from the 8[degree] casein diet rats could not inactivate estrone even in the presence of ascorbic acid, diphosphopyridine nucleotide, glutathione or liver extract. However, the 21[degree] casein diet rat livers inactivated 60[degree] in 1 1/2 hours. The data show that liver slices from the 8[degree] casein diet rats could inactivate estradiol as efficiently as liver slices from 21[degree] casein diet rats.