SYNTHESIS, METABOLISM AND SECRETION OF ESTROGENS IN THE HUMAN TERM PLACENTA.
Item
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Title
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SYNTHESIS, METABOLISM AND SECRETION OF ESTROGENS IN THE HUMAN TERM PLACENTA.
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Identifier
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AAI8611349
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identifier
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8611349
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Creator
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GULLER, SETH MARK.
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Contributor
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Erlio Gurpide
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Date
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1986
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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 | Biology, Animal Physiology
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Abstract
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This dissertation describes studies of metabolism and distribution of estrogens in the human placenta, conducted both at the subcellular and the whole organ levels.;Initially, preparations of microvillar membranes (i.e., microvillar vesicles from which cytoplasmic contamination has been removed) were employed to successfully search for plasma membrane associated enzymes involved in steroid metabolism (17(beta) dehydrogenases and sulfatases). Differences in kinetic characteristics for the dehydrogenation at C-17 of testosterone (T) and estradiol (E(,2)) were found in microvillar, microsomal, cytosolic and mitochondrial fractions. Comparison of pH optima for activity for the cytosolic and microvillar enzymes also revealed significant differences. The molecular weight of microvillar E(,2) 17(beta) dehydrogenase (E(,2)DH), estimated by gel filtration on Sephadex G-100 was found to be 137,000, approximately twice that observed for the cytosolic enzyme. However, similar isoelectric points were found for the cytosolic and the solubilized microvillar enzyme. Studies with trypsin and with antibody to purified cytosolic E(,2)DH revealed that both microvillar sulfatase and E(,2)DH enzymes are protected in the microvillar membrane environment. Although placental microvilli were a rich source of steroid metabolizing enzymes, specific binders for E(,2) were not found at this site.;In experiments in which labeled estrone (E(,1)), E(,2), and estriol (E(,3)) were generated within the syncytium during simultaneous maternal and fetal perfusion of isolated term placentas with unconjugated precursors, two major observations were made: (1) the distribution of ('3)H-E(,1), ('3)H-E(,2), and ('3)H-E(,3) between "fetal" and "maternal" perfusates was unexpectedly different for each compound and (2) ethynyl estradiol (EE), a competitor of estrogen binding, provoked a large and selective release of ('3)H-E(,2) to the "fetal" perfusate in placentas labeled with E(,1) and E(,2). This phenomenon was repeated using a variety of estrogen precursors and binding competitors as well as different perfusion conditions. These data are consistent with a model which depicts both the binding and metabolism of E(,2) at sites within the capillary endothelium.;It was suggested that steroid binding and/or metabolizing activities at the level of the microvillar membrane or capillary endothelium can influence the amount and potency of estrogen delivered to mother and fetus.
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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
