—Alcohol:NAD oxidoreductase (EC 1.1.1.1) was studied in brain cortex, hypothalamus, cerebellum and midbrain of adult and immature rats, and in the whole encephalon of neonatal rats. The rats used in this study were (i) from a colony which has been given 12% (v/v) aqueous ethanol as the only fluid for 54 generations (‘E.F.’ rats); (ii) rats removed from this colony after the forty‐eighth generation and thereafter fed water instead of the alcohol solution (‘E.F./H2O’ rats); and (iii) normal rats. Enzyme activity in the 20,000 g supernatant of tissue homogenates was measured by the method of Raskin and Sokoloff. Activity was found to be highest in neonatal rat brain and to decrease as the age increased. Activity in the hypothalamus of adult E.F. rats was significantly higher than that found in the same region of adult E.F./H2O rats. Immature rat cerebellum alcohol:NAD oxidoreductase activity was higher both in ‘E.F.’ and ‘E.F./H2O’ suggesting a possible genetic change be involved in this CNS region. It may be concluded that, with the exception of neonatal rats, ethanol consumption induces an increase in rat CNS alcohol :NAD oxidoreductase activity.
CONJUNCTIVE TUMORIGENESIS AND ESTROGENS 467.absorbed daily per square millimeter of a tablet of free estradiol. A similar quantity of estradiol was available daily from one square millimeter of a tablet ofl dipropionate (1.1 to 1.6 y), i. e., the rate of absorption was, in our experiments, so greatly enhanced by combination with propionic acid that a tablet of dipropionate gave up per day and per square millimeter the same number of molecules of estradiol as a tablet of the free hormone. On the contrary, five to six times less was absorbed daily per square millimeter of a tablet of caprylate. This would explain why dipropionate of estradiol is so similar to estradiol in the estrous test in the rat whereas other esters are much less estrogenic.$ Summary. The'rate of absorption of free estradiol, and dipropionate and caprylate of estradiol from subcutaneously implanted tablets has been studied in the guinea pig. The average percentage absorption per day was very similar to that found .by Emmens in the rut. Average percentage absorption from 17-caprylate tablets was 3 times less than that from tablets of free estradiol. On the contrary, average percentage of absorption from dipropionate tablets was greater than frdm estradiol tablets. Combination of estradiol with two molecules of propionic acid so greatly enhanced the percentage absorption in the guinea pig that the number of molecules of estradiol available from one square millimeter of a dipropionate tablet became similar to that available from one square millimeter of a tablet of the free hormone.As with natural follictllar hormones, free or esterifid, a prolonged treatment with an artifi@2al estrogen, such as stilbestrd, will induce a Miescher, K., Scholz, C., and Tschopp, E., Biochem. J., 1938, 82, 725.
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