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.
Deanesly and Parkes made use of their ingenious method of subcutaneously implanted tablets to study the question of the rate of hormone absorption. Emmensl has recently communicated important results on the comparative rate of absorption of estrogens and androgens and their esters in the rat.In the course of our work on the fibromatogenic action of a prolonged treatment with estrogens in the guinea pig, we have applied the method of Deanesly and Parkes with most satisfactory results2 In this way, we also became interested in the rate of absorption of different hormones. In the present paper, we shall give the results obtained in 52 female guinea pigs with 3 estrogens: free estradiol, dipropionate of estradiol and 17-caprylate of estradiol. Our results (Table I ) which confirm those of Emmens, present new relevant details and render it possible to compare the rate of absorption in two different species.The range of weight of the disc-shaped tablets, or their fragments, was the same in all 3 groups, and range of surface was very likely the same. This is important because absorption is related to the surface. There was considerable scattering of percentage of absorption in each of these three groups (fifth row of Table I and Fig. l ) , but it is remarkable that the range of scattering of percentage of absorption coincided with the range of weight of tablets in the respective group (fourth row of Table I, figures in parentheses). The smaller or the thinner a tablet, the greater the surface in relation to the weight and the greater also the percentage of absorption.The average absorption of estradiol was 20% in 73 days, or 0.28% per day (sixth row of Table I). The caprylate tablets lost 6.1 % in 74 days or 0.08% per day.
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