DOCSLIB.ORG

Control of Steroid, Heme, and Carcinogen Metabolism by Nuclear Pregnane X Receptor and Constitutive Androstane Receptor

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Control of Steroid, Heme, and Carcinogen Metabolism by Nuclear Pregnane X Receptor and Constitutive Androstane Receptor Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor Wen Xie*†‡, Mei-Fei Yeuh‡§, Anna Radominska-Pandya¶, Simrat P. S. Saini*, Yoichi Negishi*, Bobbie Sue Bottroff†, Geraldine Y. Cabrera†, Robert H. Tukey§, and Ronald M. Evans†ʈ *Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213; †Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; §Laboratory of Environmental Toxicology, Departments of Chemistry, and Biochemistry and Pharmacology, University of California at San Diego, La Jolla, CA 92093; and ¶Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 Contributed by Ronald M. Evans, December 31, 2002 Through a multiplex promoter spanning 218 kb, the phase II UDP- ogens, estrogen, and thyroxin metabolism. Moreover, activation of glucuronosyltransferase 1A (UGT1) gene encodes at least eight dif- PXR in transgenic mice is sufficient to increase levels of UGT ferently regulated mRNAs whose protein products function as the expression and activity, as well as bilirubin and steroid clearance. principal means to eliminate a vast array of steroids, heme metabo- lites, environmental toxins, and drugs. The orphan nuclear receptors Materials and Methods pregnane X receptor (PXR) and constitutive androstane receptor Animals. The generation of VP-hPXR, hPXR (previously known as (CAR) were originally identified as sensors able to respond to numer- VPSXR and SXR) transgenic mice and PXR null mice has been ous environmentally derived foreign compounds (xenobiotics) to described (8). promote detoxification by phase I cytochrome P450 genes. In this report, we show that both receptors can induce specific UGT1A UGT1A1 Promoter Cloning and Site-Directed Mutagenesis. The hu- isoforms including those involved in estrogen, thyroxin, bilirubin, and man UGT1A1 promoter was amplified by using a BAC clone carcinogen metabolism. Transgenic mice expressing a constitutively containing the entire UGT1 locus template (2). All primers were active form of human PXR show markedly increased UGT activity designed based on the sequence encoding the human UGT1A locus toward steroid, heme, and carcinogens, enhanced bilirubin clearance, published in the National Center for Biotechnology Information as well as massively increased steroid clearance. The ability of PXR and GenBank (accession no. AF297093). Site-directed mutagenesis was constitutive androstane receptor and their ligands to transduce both performed by PCR and confirmed by DNA sequencing. the phase I and phase II adaptive hepatic response defines a unique transcriptional interface that bridges the ingestion and metabolism of DNA-Binding Analysis. Electrophoretic mobility-shift assays environmental compounds to body physiology. (EMSA) were performed by using in vitro-transcribed and -trans- lated protein (TNT, Promega) as described (14). Oligonucleotides Ј he metabolism of steroid hormones, other endogenous com- were: UGT1A1, 5 -CTAACGGTTCATAAAGGGTATTAGGT- 3Ј; UGT1A6, 5Ј-CGAGTAGGTCATAAAGGTCACA-3Ј; and Tpounds, and xenobiotics occurs in the hepatogastrointestinal Ј Ј tract. This catabolic process is mediated by phase I enzymes, such UGT1A6m, 5 -CGAGTAGAACATAAAGAACACA-3 . as the monooxygenase CYP enzymes (1), as well as the phase II ͞ conjugating enzymes, such as UDP-glucuronosyltransferase Plasmid Construction and Transfection. The tk-UGT1A6 DR3-Luc (UGTs), sulfotransferases, and GSTs (2). The UGT 1A (UGT1A) and its mutant variants were generated by insertion of correspond- locus is controlled by 13 promoters (A1–A12), spanning Ͼ200 kb ing annealed oligonucleotides into the tk-Luc vector. The expres- of upstream sequence encoding overlapping but distinct mRNAs sion vectors for hPXR, VP-hPXR, and VP-CAR have been (3). Using UDP-glucuronic acid as a cosubstrate, UGT enzymes described (14). CV-1 cell transfection using N-[1-(2,3-dioleoy- convert a diverse set of lipophilic substances to water-soluble loxy)propyl]-N,N,N-trimethylammonium methylsulfate (Roche glucuronides and function as the principal means to eliminate Biochemicals) and HepG2 cell transfections using Lipofectamine steroids, heme metabolites, environmental toxins, and drugs from Plus (Invitrogen) were carried out as before (14, 15). the body (2). Crigler–Najjar syndrome type I results in a lethal Northern and Western Blot Analysis. accumulation of bilirubin due to a defect in the 1A1 promoter, Total RNA was prepared from liver tissues by using TRIzol reagent (Invitrogen). Northern hy- whereas Gilbert’s disease (7% of the population) is a more mild 1A1 bridization was carried out as described (8). Liver microsomes were promoter defect typified by increased sensitivity to certain drugs prepared and analyzed for UGT1A expression. Western blot pro- like Tylenol (2). files were conducted by using an anti-UGT1A antibody, which Nuclear receptor (NR) pregnane X receptor (PXR, also known recognizes only the UGT1A family of proteins, and an anti- as the steroid and xenobiotic receptor or SXR) and the constitutive UGT1A1 antibody that is specific for UGT1A1. androstane receptor (CAR) were originally shown to act through NR response elements localized in the promoters of the target UGT Analysis. The UGT analysis was similar to that described before CYP3A and CYP2B genes (4–10). Pharmaceutical compounds (16). In brief, mouse liver microsomes were prepared as described such as phenobarbital and rifampicin (RIF) have been reported as (16). The [14C]UDP-GlcUA was used as the sugar donor, and TLC UGT inducers, although the molecular basis remains to be defined was used to separate glucuronidation products. The products were (11, 12). Both phenobarbital and RIF have been empirically used to treat hyperbilirubinemia, a clinical accumulation of serum bili- rubin due to insufficient glucuronidation (11, 13). These com- Abbreviations: CAR, constitutive androstane receptor; PXR, pregnane X receptor; RIF, pounds are activators of PXR and CAR, suggesting a plausible rifampicin; TCPOBOP, 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene; UGT, UDP-glucurono- signaling pathway for UGT transcription. syltransferase; NR, nuclear receptor; EMSA, electrophoretic mobility-shift assay. In this report, we show that both receptors can induce specific ‡W.X. and M.-F.Y. contributed equally to this work. UGT1A isoforms including those specialized for bilirubin, carcin- ʈTo whom correspondence should be addressed. E-mail: [email protected]. 4150–4155 ͉ PNAS ͉ April 1, 2003 ͉ vol. 100 ͉ no. 7 www.pnas.org͞cgi͞doi͞10.1073͞pnas.0438010100 Downloaded by guest on October 3, 2021 MEDICAL SCIENCES Fig. 1. Induction of UGT1A expression and glucuronidation by PXR activation. (A) Liver microsomes were prepared from WT and VP-hPXR transgenic mice and subject to Western blot profiling by using a pan anti-UGT1A antibody and a specific anti-UGT1A1 antibody. (B) Mouse liver total RNAs were subjected to Northern blot analysis. The membranes were probed for UGT1A6, UGT1As, CYP3A11, and GAPDH as a loading control. (C) Induction of UGT1A mRNA by RIF in hPXR transgenic mice. WT or transgenic males were gavaged with a single dose of solvent or RIF (50 mg͞kg) 24 h before death. (D) The parental HepG2 cells or the HepG2-hPXR stable cells were treated with DMSO or 25 ␮M RIF for 24 h and subsequently harvested for Northern blot analysis to detect UGT1A1 mRNA. (E) Glucuronidation activity toward ␤-estradiol. The result is shown as the autoradiograph of a TLC plate. (F) Glucuronidation toward thyroid hormones (rT3 and T4) and xenobiotics (4-nitrophenol and 4-OH-PhIP). Results are presented as fold increase in glucuronidation activity over WTs and represent the mean and standard error. visualized with a Molecular Dynamics Storm 820 PhosphorImager. at 4 p.m. by retroorbital eye bleeding within 1 min of initial Alternatively, silica gel in zones corresponding to the glucuronide disturbance. The 24-h urine was collected by using mouse metabolic bands were visualized by autoradiography, or corresponding areas cages (Nalge). Corticosterone levels in plasma or urine were from control lanes were scraped into scintillation vials, and radio- measured with a Corticosterone [125I]RIA kit from ICN. The activity was measured by liquid scintillation counting. statistical analysis was performed with INSTAT 2.03 software. Bilirubin Clearance. Adult males were given a single does of bilirubin Results (10 mg͞kg body weight). Blood samples were collected in untreated tubes1hafterinjection.Serumwasprepared by centrifugation at Activation of PXR Induces UGT Expression and Glucuronidation in 4,000 rpm for 10 min. Total and conjugated bilirubin levels were Transgenic Mice. The regulatory locus of the UGT1A gene is highly measured by Antech Diagnostic (Lake Success, NY). The statistical complex. It harbors 12 promoters that control the independent analysis was performed with INSTAT 2.03 software. expression of a specific UGT isoform with distinctive substrate specificity (2). The isoforms vary at the amino terminus and Blood and Urine Collection and Hormone Analysis. Mouse blood share a common body coded by exons 2–5. For example, the 1A1 samples were collected in EDTA-coated tubes (Becton Dickinson) isoform metabolizes estrogens but not androgens or other Xie et al. PNAS ͉ April 1, 2003 ͉ vol. 100 ͉ no. 7 ͉ 4151 Downloaded by guest on October 3, 2021 Fig. 2. Cloning of the UGT1A1 gene
Load more

Recommended publications
  • Seco-Steroids C07C)
    CPC - C07J - 2021.08 C07J STEROIDS (seco-steroids C07C) Definition statement This place covers: Compounds containing a cyclopenta[a]hydrophenanthrene skeleton (see below) or a ring structure derived therefrom: • by contraction or expansion of one ring by one or two atoms; • by contraction or expansion of two rings each by one atom; • by contraction of one ring by one atom and expansion of one ring by one atom; • by substitution of one or two carbon atoms of the cyclopenta[a]hydrophenanthrene skeleton, which are not shared by rings, by hetero atoms, in combination with the above defined contraction or expansion or not, or; • by condensation with carbocyclic or heterocyclic rings in combination with one or more of the foregoing alterations or not. Preparation of steroids including purification, separation, stabilisation or use of additives unless provided for elsewhere, as specified below. Treatment and modification of steroids provided that • the treatment is not provided for elsewhere and • the resultant product is a compound under the subclass definition. Relationships with other classification places In class C07, in the absence of an indication to the contrary, a compound is classified in the last appropriate place, i.e. in the last appropriate subclass. For example cyclopenta [a] hydrophenantrenes are classified in subclass C07J as steroids and not in subclasses C07C or C07D as carbocyclic or heterocyclic compounds. Subclass C07J is a function-oriented entry for the compounds themselves and does not cover the application or use of the compounds under the subclass definition. For classifying such information other entries in the IPC exist, for example: Subclass A01N: Preservation of bodies of humans or animals or plants or parts thereof; biocides, e.g.
    [Show full text]
  • Proceedings of the Thirtieth Annual Meeting of the American Society for Clinical Investigation Held in Atlantic City, N
    PROCEEDINGS OF THE THIRTIETH ANNUAL MEETING OF THE AMERICAN SOCIETY FOR CLINICAL INVESTIGATION HELD IN ATLANTIC CITY, N. J., MAY 2, 1938 J Clin Invest. 1938;17(4):501-537. https://doi.org/10.1172/JCI100977. Research Article Find the latest version: https://jci.me/100977/pdf PROCEEDINGS OF THE THIRTIETH ANNUAL MEETING OF THE AMERICAN SOCIETY FOR CLINICAL INVESTIGATION HELD IN ATLANTIC CITY, N. J., MAY 2, 1938 READ BEFORE THE SCIENTIFIC SESSION The Successful Treatment of Pernicious Anemia by in powdered form hemostasis was readily obtained in Means of Non-Autolyzed Yeast. By MAXWELL M. hemorrhages following nine dental extractions and three WINTROBE, Baltimore, Md. external wounds in five hemophilic subjects. When ap- It has been the general opinion that yeast, if it pos- plied in liquid form as other hemostatics are usually em- sesses any antianemic potency whatever, is effective only 1 loyed the results were unsatisfactory. Since the co- after autolysis and then only by virtue of its content of agulation time of the circulating blood was unchanged the "extrinsic factor." The observations reported contradict effectiveness of powdered beef globulin substance when this view and indicate that dehydrated yeast which has locally applied to a bleeding wound in hemophilia is not been subjected to autolysis, contains an antiper- attributed to the rapid formation of a firm fibrin clot. nicious anemia substance. Yeast obtained from two dif- The failure of liquid preparations may be due to the ferent sources was effective in the treatment of classical inability to maintain a sufficient concentration of the cases of pernicious anemia.
    [Show full text]
  • Nomenclature of Steroids
    Pure&App/. Chern.,Vol. 61, No. 10, pp. 1783-1822,1989. Printed in Great Britain. @ 1989 IUPAC INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY and INTERNATIONAL UNION OF BIOCHEMISTRY JOINT COMMISSION ON BIOCHEMICAL NOMENCLATURE* NOMENCLATURE OF STEROIDS (Recommendations 1989) Prepared for publication by G. P. MOSS Queen Mary College, Mile End Road, London El 4NS, UK *Membership of the Commission (JCBN) during 1987-89 is as follows: Chairman: J. F. G. Vliegenthart (Netherlands); Secretary: A. Cornish-Bowden (UK); Members: J. R. Bull (RSA); M. A. Chester (Sweden); C. LiCbecq (Belgium, representing the IUB Committee of Editors of Biochemical Journals); J. Reedijk (Netherlands); P. Venetianer (Hungary); Associate Members: G. P. Moss (UK); J. C. Rigg (Netherlands). Additional contributors to the formulation of these recommendations: Nomenclature Committee of ZUB(NC-ZUB) (those additional to JCBN): H. Bielka (GDR); C. R. Cantor (USA); H. B. F. Dixon (UK); P. Karlson (FRG); K. L. Loening (USA); W. Saenger (FRG); N. Sharon (Israel); E. J. van Lenten (USA); S. F. Velick (USA); E. C. Webb (Australia). Membership of Expert Panel: P. Karlson (FRG, Convener); J. R. Bull (RSA); K. Engel (FRG); J. Fried (USA); H. W. Kircher (USA); K. L. Loening (USA); G. P. Moss (UK); G. Popjiik (USA); M. R. Uskokovic (USA). Correspondence on these recommendations should be addressed to Dr. G. P. Moss at the above address or to any member of the Commission. Republication of this report is permitted without the need for formal IUPAC permission on condition that an acknowledgement, with full reference together with IUPAC copyright symbol (01989 IUPAC), is printed.
    [Show full text]
  • Medical Treatment of Hirsutism in Women F
    2530 Current Medicinal Chemistry, 2010, 17, 2530-2538 Medical Treatment of Hirsutism in Women F. Lumachi*,1 and S.M.M. Basso2 1Department of Surgical and Gastroenterological Sciences; 21st School of General Surgery, University of Padua, School of Medicine, 35128 Padova, Italy Abstract: Hirsutism is the presence of excess hair growth in women in the typical male hair growth areas, thereby reflect- ing a deviation from the normal female hair pattern. It affects from 5% to 10% of women, depending on age, menopausal status and ethnic background. The presence of hirsutism is very distressing for women, and subsequently may have a negative impact on their psychosocial life. In the treatment of hirsutism several options are now available, including pharmacologic regimens and cosmetic measures. Both the hormonal profile of the patient and her expectations and prefer- ences should guide the therapeutic approach. The aims of the medical therapy are suppression of excessive androgen pro- duction, inhibition of peripheral action of androgens, and treatment of patients at risk for metabolic disorders or reproduc- tive cancers. For other diseases related to endocrine abnormalities, such as thyroid disorders or Cushing’s syndrome, spe- cific treatment is mandatory. After an ineffective local approach by direct hair removal, a pharmacological treatment should be suggested, using estrogen and progestin combinations, antiandrogens (i.e. cyproterone acetate, spironolactone) or both as a first line. Finasteride, gonadotropin-releasing hormone agonists, and glucocorticoids should be used in se- lected cases. Adequate contraception is also recommended if antiandrogens are used. Unfortunately, since systemic ther- apy reduces hair growth in less than 50% of cases, hirsute women frequently require cosmetic measures.
    [Show full text]
  • UNITED STATES PATENT OFFICE 2,231,017 ALLO-PREGNANE COMPOUNDS and METH OD of OBTAINING the SAME Russell Earl Marker, State
    Patented Feb. 11, 1941 2,231,017 UNITED STATES PATENT OFFICE 2,231,017 ALLO-PREGNANE COMPOUNDS AND METH OD OF OBTAINING THE SAME Russell Earl Marker, State. College, Pa., assignor to Parke, Davis & Company, Detroit, Mich., a corporation of Michigan No Drawing. Application March 12, 1937, Serial No. 130,582 6 Claims. (CI. 260-397) The invention relates to a new keto-alcohol of with a ketone reagent capable of reacting with the sterol series, and particularly to epi-allo the epi-allo-pregnane-ol- (3)-one- (20) but not pregnanol- (3)-One- (20) and its isolation from with the non-ketonic alcohols. mixtures with other sterol derivatives of a non 7. Separating the reaction product of step (6) 5 ketonic nature. from non-ketonic alcohols, and, It is known that the two non-ketonic alcohols 8. Decomposing the reaction product to obtain having a cyclopentano-10,13-dimethyl polyhy epi-allo-pregnane-ol- (3) -one- (20), which can drophenanthrene nucleus, pregnanediol and allo be readily separated by means of Organic Sol pregnanediol, belonging to the pregnane or pro vents from the decomposition products of this O gesterOne chemical group, may be isolated from Step. O the neutral or alcoholic fraction of human preg . The above series of eight steps is of Special nancy urine. However, no compounds of a keton value when the original mixture to be treated ic nature have been heretofore isolated from is a neutral carbinol fraction from human preg these or other like mixtures. nancy urine. In step (6) above the use of a It is an object of the invention to separate hydrazine compound capable of forming a and isolate the new ketonic alcohol, epi-allo water-soluble hydrazine derivative With the epi 5 pregnanol- (3)-One- (20), from its mixtures with allo-pregnanol- (3)-one- (20) is preferred as a pregnanediol and allo-pregnanediol or other like ketone reagent.
    [Show full text]
  • Steroid Mo~~~~Roa~~At~
    195 STEROID MO~~~~ROA~~AT~. P~S~~A~H~~~ CHARACTERISTICS AND USE IN GAS-LIQWID CRROMATOGRU'HP, B,J* van der Roles, D, Green and J,H* van der ma@ Departments of Obstetrics and Gynecology and Analytic&i!. Chemistry, State University, Utreeht, The Rstherlands. Received May 4, 1965 Synthesis and physical-chemical characteristics (melting points, infrared-, visibIls-and ultraviolet spectra, paper-, tbin-layer- and gas-liquid chromatographicbehaviour) of mono- chloroacetate derivatives of steroids representing the andros- tans-, pregnane-, estrane- and cholestane series are described, The usefulness of these derivatives in gas-liquid chromatogra- phy isdemonstrated. Through their strong electron absorbing properties the quantitatfon of nanogram amounts of these deri- vatives by electron capture detection is possible. shortly following the preliminary introduction of the electron capture detector in gas-liquid chromatography'I, the extreme sensitivity of this detector for chlorinated cOmpOU2Xds was used in the field of pesticides21 v The general observation that introduction of halide atoms in non-electron absorbing compounds might produce positive centers for electron attaoh- 4) ment3~, prompted ~~~~ AND LIPSKY to prepare a series of cholesteryl-haloacetatos5', They demonstrated, that the electron capture detector was far more sensitive towards the chlorinated than the free compounds. The sensitivity of elec- tron capture detection of the halo-acetates was highly increased as compared with&e sensitivity of flame and argon ionization detection of the free and halo-acetylated compounds, Whereas chXoroacetates in general proved to be more sensitlva for electron capture d&e&ion than bromo- and fluoro-acetates, the detection of monoch~oroacetate~proved to be more sensiti- ve than detection of the dichloro- and trichloro-acetates, We have been able to confirm this finding in the series of chlo- roaoetates6'.
    [Show full text]
  • Creation and Preliminary Characterization of Pregnane X Receptor and Constitutive Androstane Receptor Knockout Rats
    DMD Fast Forward. Published on July 17, 2017 as DOI: 10.1124/dmd.117.075788 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 75788 TITLE: CREATION AND PRELIMINARY CHARACTERIZATION OF PREGNANE X RECEPTOR AND CONSTITUTIVE ANDROSTANE RECEPTOR KNOCKOUT RATS Authors: Kevin P Forbes, Evguenia Kouranova, Daniel Tinker, Karen Janowski, Doug Cortner, Aaron McCoy and Xiaoxia Cui Downloaded from Horizon Discovery Group Company, Saint Louis, MO 63146 dmd.aspetjournals.org at ASPET Journals on September 25, 2021 1 DMD Fast Forward. Published on July 17, 2017 as DOI: 10.1124/dmd.117.075788 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 75788 RUNNING TITLE: PXR-/- and CAR-/- knock-out rats Author for correspondence Name: Kevin P. Forbes Address: 2033 Westport Center Dr., Saint Louis, MO 63146 Email: [email protected] Downloaded from Phone: 314-400-6609 dmd.aspetjournals.org Text pages #: 25 Table #: 5 supplemental tables Figures #: 5 main figures, 6 supplemental figures at ASPET Journals on September 25, 2021 References #: 43 Word count Abstract: 234 Word count Introduction: 745 Word count Results: 1390 Word count Discussion: 1432 2 DMD Fast Forward. Published on July 17, 2017 as DOI: 10.1124/dmd.117.075788 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 75788 Abstract: The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of Phase I (Cytochrome P450s), Phase II metabolizing enzymes and transporter genes in response to stimulation from xenobiotics, including prescription drugs.
    [Show full text]
  • In Ovo Metabolism of Progesterone to 5Β-Pregnanedione in Chicken Eggs: Implications for How Yolk Progesterone Influences Embryonic Development T ⁎ Ryan T
    General and Comparative Endocrinology 282 (2019) 113221 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen In ovo metabolism of progesterone to 5β-pregnanedione in chicken eggs: Implications for how yolk progesterone influences embryonic development T ⁎ Ryan T. Paitz , Erin Cagney School of Biological Sciences, Illinois State University, Normal, IL 61790, USA ARTICLE INFO ABSTRACT Keywords: Progesterone has received substantial attention for the essential role it plays in establishing and maintaining Progestogens pregnancy in placental vertebrates. Despite the prevalence of progesterone during development, relatively little Maternal effects is known about how embryos respond to progesterone. This is true of placental vertebrates as well as egg-laying Developmental endocrinology vertebrates where levels of progesterone in the yolk tend to be higher than most other steroids in the yolk. Bird Avian eggs provide an opportunity to investigate the effects of progesterone on embryonic development because progesterone can be easily manipulated without any confounding effects on maternal physiology. To understand how progesterone might influence embryonic development, it is important to characterize the metabolic fate of progesterone given its potential to be converted to a wide range of steroids. We investigated the metabolic fate of tritiated progesterone over the first four days of development using chicken eggs (Gallus gallus) and identified 5β- pregnanedione as the primary metabolite during this period. After only one day of development, 5β-pregna- nedione could be detected within the yolk. Levels of 5β-pregnanedione in both the yolk and albumen tended to rise early in development but conjugated metabolites began to accumulate towards the end of our sampling period.
    [Show full text]
  • ACS Style Guide
    ➤ ➤ ➤ ➤ ➤ The ACS Style Guide ➤ ➤ ➤ ➤ ➤ THIRD EDITION The ACS Style Guide Effective Communication of Scientific Information Anne M. Coghill Lorrin R. Garson Editors AMERICAN CHEMICAL SOCIETY Washington, DC OXFORD UNIVERSITY PRESS New York Oxford 2006 Oxford University Press Oxford New York Athens Auckland Bangkok Bogotá Buenos Aires Calcutta Cape Town Chennai Dar es Salaam Delhi Florence Hong Kong Istanbul Karachi Kuala Lumpur Madrid Melbourne Mexico City Mumbai Nairobi Paris São Paulo Singapore Taipei Tokyo Toronto Warsaw and associated companies in Berlin Idaban Copyright © 2006 by the American Chemical Society, Washington, DC Developed and distributed in partnership by the American Chemical Society and Oxford University Press Published by Oxford University Press, Inc. 198 Madison Avenue, New York, NY 10016 Oxford is a registered trademark of Oxford University Press All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the American Chemical Society. Library of Congress Cataloging-in-Publication Data The ACS style guide : effective communication of scientific information.—3rd ed. / Anne M. Coghill [and] Lorrin R. Garson, editors. p. cm. Includes bibliographical references and index. ISBN-13: 978-0-8412-3999-9 (cloth : alk. paper) 1. Chemical literature—Authorship—Handbooks, manuals, etc. 2. Scientific literature— Authorship—Handbooks, manuals, etc. 3. English language—Style—Handbooks, manuals, etc. 4. Authorship—Style manuals. I. Coghill, Anne M. II. Garson, Lorrin R. III. American Chemical Society QD8.5.A25 2006 808'.06654—dc22 2006040668 1 3 5 7 9 8 6 4 2 Printed in the United States of America on acid-free paper ➤ ➤ ➤ ➤ ➤ Contents Foreword.
    [Show full text]
  • IUPAC. Natural Products and Related Compounds
    Pure Appl. Chem., Vol. 71, No. 4, pp. 587–643, 1999. Printed in Great Britain. ᭧ 1999 IUPAC INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY ORGANIC CHEMISTRY DIVISION COMMISSION ON NOMENCLATURE OF ORGANIC CHEMISTRY (III.1) REVISED SECTION F: NATURAL PRODUCTS AND RELATED COMPOUNDS (IUPACRecommendations1999) Prepared for publication by P. M. GILES, Jr Chemical Abstracts Service, Columbus, OH 43210, USA Membership of the Working Party (1982–1997): J. R. Bull (Republic of South Africa), H. A. Favre (Canada), M. A. C. Kaplan (Brazil), L. Maat (Netherlands), A. D. McNaught (UK), G. P. Moss (UK), W. H. Powell (USA), R. Schoenfeld† (Australia), O. Weissbach (Federal Republic of Germany). Membership of the Commission on Nomenclature of Organic Chemistry during the preparation of this document was as follows: Titular Members: O. Achmatowicz (Poland) 1979–1987; J. Blackwood (USA) 1996–1998; H, J. T. Bos (Netherlands) 1987– 1995, Vice-Chairman, 1991–1995; J. R. Bull (Republic of South Africa) 1987–1993; F. Cozzi (Italy) 1996–; H. A. Favre (Canada) 1989–, Chairman, 1991–; P. M. Giles, Jr. (USA) 1989–1995; E. W. Godly (UK) 1987–1993, Secretary, 1989–1993; D. Hellwinkel (Federal Republic of Germany) 1979–1987, Vice-Chairman, 1981–1987; B. J. Herold (Portugal) 1994–; K. Hirayama (Japan) 1975–1983; M. V. Kisaku¨rek (Switzerland) 1994–, Vice-Chairman, 1996–; A. D. McNaught (UK) 1979– 1987; G. P. Moss (UK) 1977–1987, Chairman, 1981–1987, Vice-Chairman, 1979–1981; R. Panico (France) 1981–1991, Vice- Chairman, 1989–1991; W. H. Powell (USA), Secretary, 1979–1989; J. C. Richer (Canada) 1979–1989, Vice-Chairman, 1987–1989; P.
    [Show full text]
  • EFFECT of ORAL CYPROTERONE ACETATE on URINARY and SERUM FSH and LH LEVELS in ADULT MALES BEING TREATED for HYPERSEXUALITY Univer
    EFFECT OF ORAL CYPROTERONE ACETATE ON URINARY AND SERUM FSH AND LH LEVELS IN ADULT MALES BEING TREATED FOR HYPERSEXUALITY JANET BROTHERTON Schering Chemicals Ltd, Burgess Hill, Sussex, and School of Biological Sciences, University of Sussex (Received 12th February 1973) Summary. A group of eighteen male hypersexual patients received 50 mg cyproterone acetate orally twice a day. Radioimmunoassays of LH and FSH were carried out at intervals on serum and 24-hr urine speci- mens. All the six `pretreatment' and twenty-eight `during-treatment' levels of urinary FSH fell within the normal range of 2 to 17 i.u. 2nd IRP-HMG/24 hr. One of the six `pretreatment' and three of the twenty\x=req-\ eight `during-treatment' levels of urinary LH were higher than the normal range of 4 to 50 i.u. 2nd IRP-HMG/24 hr. Treated as a whole, the LH levels could be regarded as showing no difference due to treat- ment with cyproterone acetate but if the patient with the high pre- treatment level, who was also suffering from schizophrenia, was removed from the group then the LH levels during treatment showed a significant rise. The mean serum LH was 6\m=.\3mU MRC 69/104 standard/ml with an upper limit of 14\m=.\4mU and the mean serum FSH was 13\m=.\3mi.u. 2nd IRP-HMG/ml with a range of 6 to 33 mi.u. All these results were within the quoted normal ranges. The mechanism of action of cypro- terone acetate is discussed, taking into consideration the normal LH and FSH levels, low testosterone levels and inhibition of spermatogenesis and is compared with the actions of oestrogens, androgens, `pure' pro- gestagens and `pure' anti-androgens on these parameters.
    [Show full text]
  • Introduction (Pdf)
    Dictionary of Natural Products on CD-ROM This introduction screen gives access to (a) a general introduction to the scope and content of DNP on CD-ROM, followed by (b) an extensive review of the different types of natural product and the way in which they are organised and categorised in DNP. You may access the section of your choice by clicking on the appropriate line below, or you may scroll through the text forwards or backwards from any point. Introduction to the DNP database page 3 Data presentation and organisation 3 Derivatives and variants 3 Chemical names and synonyms 4 CAS Registry Numbers 6 Diagrams 7 Stereochemical conventions 7 Molecular formula and molecular weight 8 Source 9 Importance/use 9 Type of Compound 9 Physical Data 9 Hazard and toxicity information 10 Bibliographic References 11 Journal abbreviations 12 Entry under review 12 Description of Natural Product Structures 13 Aliphatic natural products 15 Semiochemicals 15 Lipids 22 Polyketides 29 Carbohydrates 35 Oxygen heterocycles 44 Simple aromatic natural products 45 Benzofuranoids 48 Benzopyranoids 49 1 Flavonoids page 51 Tannins 60 Lignans 64 Polycyclic aromatic natural products 68 Terpenoids 72 Monoterpenoids 73 Sesquiterpenoids 77 Diterpenoids 101 Sesterterpenoids 118 Triterpenoids 121 Tetraterpenoids 131 Miscellaneous terpenoids 133 Meroterpenoids 133 Steroids 135 The sterols 140 Aminoacids and peptides 148 Aminoacids 148 Peptides 150 β-Lactams 151 Glycopeptides 153 Alkaloids 154 Alkaloids derived from ornithine 154 Alkaloids derived from lysine 156 Alkaloids
    [Show full text]