IN VITRO METABOLISM OF C19 STEROIDS IN HUMAN ENDOMETRIUM.
Item
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Title
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IN VITRO METABOLISM OF C19 STEROIDS IN HUMAN ENDOMETRIUM.
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Identifier
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AAI8302516
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identifier
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8302516
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Creator
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HAUSKNECHT, VIRGINIA ANN.
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Date
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1982
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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In order to quantitate the extent of intracellular or metabolic conversions of C(,19) steroids in human endometrium, specimens of proliferative and secretory tissue were superfused at a constant rate with several pairs of labeled compounds at low concentrations.;From these superfusions it was determined that 10 to 20% of the dehydroepiandrosterone sulfate which interacts with the endometrium is hydrolyzed to dehydroepiandrosterone, regardless of the phase of the menstrual cycle.;Testosterone and androstenedione are interconverted in endometrial tissue by 17(beta) hydroxysteroid dehydrogenase with a preference toward oxidation. Both the oxidative and reductive activities of this endometrial enzyme increase during the luteal phase of the menstrual cycle, likely under the influence of progesterone. The testosterone taken up by endometrial cells is mostly oxidized to androstenedione and released from the tissue as androstenedione, while the androstenedione taken up by the tissue is mostly removed from the tissue by diffusion.;The physiologically active androgen dihydrotestosterone is formed in endometrial tissue. It arises from the testosterone entering the cells which is directly 5(alpha) reduced (about 1%) and from the androstenedione which is first 5(alpha) reduced to androstanedione and then 17(beta) reduced to dihydrotestosterone. The intracellular concentrations of these two precursors, testosterone and androstenedione, determine the relative importance of the two pathways of 5(alpha) reduction. With a tissue concentration of testosterone larger than the tissue concentration of androstenedione, most of the testosterone is directly 5(alpha) reduced to dihydrotestosterone. Under these conditions, most of the androstenedione is still metabolized to dihydrotestosterone through androstanedione.;Other C(,19) metabolites produced by endometrial tissue are androsterone and 5(alpha)-androstane-3(alpha),17(beta)-diol.;Human endometrial cancer cells in culture contain the same enzymes capable of metabolizing C(,19) steroids as are found in normal human endometrium. The HEC-1 cell line and a unique cell culture derived from an epithelial carcinoma of the uterus of a phenotypic female with an XY genotype metabolized testosterone to androstenedione, androsterone and 5(alpha)-androstane-3(beta),17(beta)-diol. The HEC-1 cells preferentially produced 5(alpha)-androstane-3(alpha),17(beta)-diol and the XY cell culture preferentially produced androstenedione.;The results of these experiments with normal human endometrial tissue demonstrated that the conversion of the main circulating C(,19) steroids in women, i.e., dehydroepiandrosterone sulfate and androstenedione to dihydrotestosterone, the compound considered to be the true intracellular androgen, is very small.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
