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pubmed:otherAbstract |
PIP: This investigation describes metabolism of norethynodrel in the huma n endometrium, myometrium, and subcellular fractions of the myometrium. (6,7-tritiated) norethynodrel was purified by the paper chromatographic system; either benzene: hexane: methanol: water or petroleum ether: benzene:methanol:water. Uteri from 9 premenopausal women aged 22-45 years were collected immediately after surgery. Only normal tissues were used. Subcellular fractionation was carried out by differential ultracentrifugation. Measurements with identity confirmed by isotope dilution and recrystalization. The study revealed that norethynodrel is a very liable molecule, extensively metabolized by the human endometrium and myometrium. This tissues can convert labeled northynodrel to norethindrone; 17 alpha-ethinyl-3 alpha, 17 beta dihydroxy-5(10)-estrone: and 2 other unidentified metabolities. Under in vitro conditions 80-90% of the labeled norethynodrel was converted to its metabolities within 90 minutes. The metabolities formed were the same for both the endometrium and the myometrium. This conversion was more in the proliferative phase than in the secretary phase. Among the subcellular fractions of the myometrium, mitochondrial and microsomal fractions metabolized norethynodrel to norethindrone and 2 polar metabolities with low chromatographic mobility. In the myometrial 20500 x g supernatant fraction, 17alpha-ethinyl-3 alpha, 17 beta dihydroxy-5(10)-estrone was found in addition to norethindrone and the polar metabolities. Norethindrone is a potent progestin. This conversion was an enzymatic process. Such action of norethynodrel and its metabolities on the endometrium may distrub the biochemical make-up of the endometrium and thus prevent implantation.
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