The Effects of Exogenous ACTH on 5-3B-Hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland

Total Page:16

File Type:pdf, Size:1020Kb

The Effects of Exogenous ACTH on 5-3B-Hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland Loyola University Chicago Loyola eCommons Master's Theses Theses and Dissertations 1968 The Effects of Exogenous ACTH on 5-3b-hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland Grover Charles Ericson Loyola University Chicago Follow this and additional works at: https://ecommons.luc.edu/luc_theses Part of the Medicine and Health Sciences Commons Recommended Citation Ericson, Grover Charles, "The Effects of Exogenous ACTH on 5-3b-hydroxysteroid Dehydrogenase Activity in the Embryonic Avian Adrenal Gland" (1968). Master's Theses. 2264. https://ecommons.luc.edu/luc_theses/2264 This Thesis is brought to you for free and open access by the Theses and Dissertations at Loyola eCommons. It has been accepted for inclusion in Master's Theses by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. Copyright © 1968 Grover Charles Ericson THE EFFECTS OF EXOGENOUS ACTH ON d -JB-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN THE EMBRYONIC AVIAN ADRENAL GLAND by Grover Charles Ericson A The.is Submitted to the Faculty ot the Graduate School of La.vo1. University in Partial Fulfillment ot the Requirements for the Degree ot Master ot Science February 1968 BIOGRAPHY Grover Charles Ericson was born in Oak Park, D.linois, on February 17. 1941. He •• graduated f'rom the Naperville COIIUlIW1ity High School, Naperville. D.l1nois in June, 19.59. He entered North Central College, Naperville. Illinois, in September, 19.59, and was awarded the Bachelor of Arts degree in June, 1964. While attending North Central College. the author lllBrried a fellow student, the former Miss Barbara Joye Hoed •• In September, 1964, he began his graduate studies in the Department of' Anatomy, Loyola University Strltch School of Medicine, Chicago. llllnois. ii The author wishes to express his sincere appreoiation to his adviaor. Dr. Lincoln V. DOllDll, Protessor ot Anatomy, and Chairman, Department ot Anatomy, Emeritus, tor his approval of the probl•• 1nTalwable help, guidance and encouragement throughout thia investigation. The author would also like to expre.s hi. appreciation to Dr. Lealie A. Ehmert, Asslatant Prote.sor ot Anatany. tor h1a helpful critlciam and sug­ gestions on histochemical problema, to Dr. Robert C. Clawon. A.sistant Pro­ feasor ot Anatomy tor his advice and counael on avian embryology; and to Dr. Lucia Smelte, Senior Technician in the Department of Anatomy tor her help and counce! in preparing the histological material. Last, but not least, I would like to take th1a opportunity to expre.s my profound gratitude to my w1!e, Barbara. tor the aid. understanding and encouragement so generously provided. Th1a study WlS supported in part by USPBS, NIH, Reaearch Grants AM 03895 and AM 09926, and a USPBS, NIH, General Re.earch Support Grant. The Grants were administered by' Dr. Lincoln V. Damm. i11 TABLE OF CONTENTS Page INTRODUCTION........................................................ 1 REVI&i OF TliE Lnw.TtJRE............................................. 4 Early Development of the Adrenal Glanda........................ 4 The Adrenal Cortex........................................ 4 The Adrenal Me~....................................... ? Adrenal Steroid Production..................................... 8 H1atochami.tr.y ••••••••••••••••••••••••••••••••••••••••••••••••• 10 Ad renal-P1tu1 ta ry- Axia...... • • • • • • • • • • • • • • • • • •• • • • • • • • • • • • • • • • • 1.3 MATERIALS AND METHODS •••••••• •••••••••••••••••••••••••••••••••••••• 20 OBS.E:R.VATIONS ..................... 41' ............ .. ••••••••••••••••••••• 25 Early Development of the Adrenal Gland ..•...•..•....•.•..•..... 25 Development ot Adrenal~-3B-BSD Activity•••••••••••••••••••••• 28 Histochemical Method tor d-.3B-HSD Uaing DBA as the Substrate.. 28 Histochemical Method tor d -3B-HSD Using Pregnenolone as the Substrat••••••••••••••••••••••••••••••••••••••••••••••••••••••• )0 Effecta of Exogenous ACTH on Adrenal d_.3B-HSD Activity........ )0 Stage 22 Embr.7os •••••••••••••••••••••••••••••••••••••••••• J1 stage 23 ~os •••••••••••••••••••••••••••••••••••••••••• 31 stage 23-24 Embry-o ••••••••••••••••••••••••••••••••••••••••• .32 Stage 24 Embr.yoa •••••••.•••••••••••••••••••••••••••••••••• J2 stage 25 Embry-o ••••••••••••••••••••••••••••••••••••••••••• )3 DISCUSSION •••••••••••••••••••••••••••••••••••••••••••.•••••••.•••••• )4 iv TABLe OF CONTENTS (cont'd) Page SUMMARI AND CONCLUSIONS............................................... 40 LITERATURE CITED ••••••••••••••••••••••••••••••••••••••• ~ •••••••••••••• 42 TABLES •••••••••••••••••••••••••.••••.••.•••.•••••••••••••••••••••••••• 48 PLATES AND FIGURES ••••.••••••••••••••••••.•••.••••••••.••••••••••••••• 57 v LIST OF TABLES Table Page 1 MORPHOLOGICAL AND CHRONOLOGICAL AGES OIt' BRa.ffl .AND ~mrrE LEGHORN EMBRyOS ••••••.•••••••••••••••••••••••••••••••••••••••••• 48 2 INTENSITY OF A.DREHAL FORMAZAN DEPOSITION IN d-JB_HSD PREPkRATIONS.................................................... ;0 J TREAT.MEh~ OF STAGE 22 EMBRyOS •••••••••••••••••••••••••••.••••••• 52 4 TREATMENT OF STAGE 23 E1~OS................................... 5) 5 TREATMENT OF STAGE 23-24 ru~yOS................................ 54 6 TREATMENT OF STAGE 24 ru~yos ••••••••••••••••••••••••••••••••••• 55 ? TREATMENT or STAGE 25 ~~yos................................... 56 LIST OF FIGURES FIGURES Pi.Gli: 1 CROSS SECTION OF it. STAGE 21 BROWN LEGHORN ENBRYO............... 57 2 CROSS SECTION OF it. STAGE 22 BRO~~ LEGHORN EMBRYO............... 57 3 A HIGHER MAGNIFICATION OF THE STA.GE 22 BRCHlN LEGHORN E.t1BRIO SHOWN IN FIGURE TWO............................................ 57 4 CROSS SECTION or A STAGE 23 BROWN LEGHORN EMBRyo............... 57 5 A HIGHER MAGNIFICATION OF THE STAGE 23 ~1i LEGHORN EMBRYO SHOWI II FIGURE FOUR........................................... 57 6 CROSS SECTION OF A STAGE 24 BROWN LEGHCIUf EMBRyO............... .58 7 A HIGHER MAGNIFICATION OF THE STAGE 24 BROWN LEGHORN EMBRYO SHOWN IN FIGURE SIX............................................ 58 8 CROSS SECTION or it. STAGE 25 BRaiN LEGHORN mmRYO............... 58 9 CROSS SECTION OF A STAGE 26 WHITE LEGHORN EMBRYO............... 58 10 CROSS SECTION or A STAGE '2:l BROWN LEGHORN EMBRyO............... .58 11 CROSS SECTION OF A STAGE 28 BROWN Lb13HORN EMBRyo............... 59 12 A HIGHER MAGNIFICATION OF THE ADRENAL OF THE STAGE 28 BROWN LEGHORN EMBRYO JHOWN IN FIGUP~ ELEVEN.......................... 59 13 CROSS SECTION OF THE ADRENAL OF A STAGE 29 WHITE LEGHORN EMBRYO .......................................... or • • • • • • • • • • • • • • • • 59 14 CROSS SECTION or THE ADRENAL or A STAGE 30 WHITE LEGHORN ~\fBRYO. • • • • • • • • • •• • • • • • • • • • • •• • • • • • • • • • • • • • • • • • • • • • • •• •• •• • • • • • 59 1.5 CROSS SEeTIO» OF THE ADRENOCORTICAL CELL MASS OF A STAGE 23 COKTROL BROWH LEGHORN EMBRYO INCUBA.TED WITH DEHIDROEPIAN- DROSTERONE (DBA)............................................... 60 16 CROSS SECTION OF THE ADRENOCORTICAL CELL 11ASS OF J,. STAGE 2,3 ACTH TREATED BRC1NN LEGHORN DmRYO SACRIFICED FIVE HOURS P~"T- INJECTION AND INCUBATED WITH DBA............................... 60 LIST OF FIGURES (oonttd) FIGURES PAGE 17 CROSS SECTION OF THE ADRENOCORTICAL CELL }1ASS OF A STAGE 23- 24 CONTROL BRCWH LEGHORN EMBRYO INCUBATED WITH DBA.............. 60 18 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 23- 24 ACTH TREATED BROtlH LEGHORB EMBRYO SACRIFICED THREE HOURS POST.INJECTION AND INCUBATED WITH DI~.••••••••••••••••••••••••••• 60 19 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 24 CONTROL BROWN LEGHORN EMBRYO INCUBATED WITH DHA ••••••••••••••••• 60 20 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 24 ACTH TREATED BROWN J.EGHORN EMBRYO SACRIFICED FOUR HOURS POST- INJECTION AND INCUBATED WITH DHA •••••••••••••••••••••••••••••••• 60 21 CROSS Sl!.'C1'ION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 24 CONTROL WHITE LEGHORN EMBRYO INCUBATED WITH DNA ••••••••••••••••• 61 22 CROSS SECTION OF THE ADREHOCORTICAL CELL MASS OF A STAGE 25 CONTROL BROWN LEGHORN EMBRYO INCUBATED WITH DRA ••••••••••••••••• 61 23 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 25 ACTH TREATED BRCWN LEGHORN EMBRYO SACRIFICED FIVE HOURS P~'T- INJECTION AND INCUBATED WITH DRA ••••• ..........•............... 61 24 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 25 ACTH TREATED BR(ltIN LEGHORN EMBRYO SACRIFICED 2.5 HOURS POS'T .. INJECTION AND INCUBATED WITH DBA... • • • • • • • • • • •• • • • •• • • • • • • • • • • • • 61 25 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 23 CONTROL BR(7NN LEGHORN .l!.'MBRYO INCUBATED -VIITH PREGNENOLONE. • • • • • • • 62 26 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF THE STAGE 23 CONTROL BROWN LEGHORN EMBRYO SHGIN IN FIGURE 2.5 IHCUBATED \rlITH DHA.. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 62 27 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF A STAGE 27 CONTROL BROWN LEGHORN EMBRYO INCUBATED WITH PREGNENOLONE........ 62 28 CROSS SECTION OF THE ADRENOCORTICAL CELL MASS OF THE STAGE 27 CONTROL BRCWN LEGHORN EMBRYO SHOWN IN FIGURE 27 INCUBATED WITH DBA •••••.•••••••••••••••••••••••••••••••• * • • • • • • • • • • • • • • • •• 62 viii ABSTRACT This investigation concerned itself primarily with the development ot adrenal d-JB-hydr0JE;Y8teroid dehydrogenase (d-3B-HSD) aotivity and the effects of exogenous
Recommended publications
  • Three-Dimensional Structure of Holo 3A,20J3-Hydroxysteroid
    Proc. Nati. Acad. Sci. USA Vol. 88, pp. 10064-10068, November 1991 Biochemistry Three-dimensional structure of holo 3a,20j3-hydroxysteroid dehydrogenase: A member of a short-chain dehydrogenase family (x-ray crystaflography/steroid-metabolizing enzyme/dinucleotide-linked oxldoreductase/sterold-protein interaction/sequence and folding homologies) DEBASHIS GHOSH*t, CHARLES M. WEEKS*, PAWEL GROCHULSKI*t, WILLIAM L. DUAX*, MARY ERMAN*, ROBERT L. RIMSAY§, AND J. C. ORR§ *Medical Foundation of Buffalo, 73 High Street, Buffalo, NY 14203; and Memorial University of Newfoundland, St. John's, Newfoundland, Canada AlB 3V6 Communicated by Herbert A. Hauptman, July 18, 1991 (receivedfor review May 14, 1991) ABSTRACT The x-ray structure of a short-chain dehy- the substrate binding regions, offers further insight concern- drogenase, the bacterial holo 3a,20/3-hydroxysteroid dehydro- ing the significance of conserved residues and their possible genase (EC 1.1.1.53), is described at 2.6 A resolution. This roles in substrate specificity and overall enzyme function. enzyme is active as a tetramer and crystallizes with four identical subunits in the asymmetric unit. It has the a/( fold characteristic ofthe dinucleotide binding region. The fold ofthe MATERIALS AND METHODS rest of the subunit, the quarternary structure, and the nature The crystals, grown in the presence of 4 mM NADH, belong ofthe cofactor-enzyme interactions are, however, significantly to the space group P43212 having unit cell dimensions a = different from those observed in the long-chain dehydrogena- 106.2 A and c = 203.8 A and contain one full tetramer (106 ses. The architecture of the postulated active site is consistent kDa) in the asymmetric unit (13).
    [Show full text]
  • 1970Qureshiocr.Pdf (10.44Mb)
    STUDY INVOLVING METABOLISM OF 17-KETOSTEROIDS AND 17-HYDROXYCORTICOSTEROIDS OF HEALTHY YOUNG MEN DURING AMBULATION AND RECUMBENCY A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN NUTRITION IN THE GRADUATE DIVISION OF THE TEXAS WOI\IIAN 'S UNIVERSITY COLLEGE OF HOUSEHOLD ARTS AND SCIENCES BY SANOBER QURESHI I B .Sc. I M.S. DENTON I TEXAS MAY I 1970 ACKNOWLEDGMENTS The author wishes to express her sincere gratitude to those who assisted her with her research problem and with the preparation of this dissertation. To Dr. Pauline Beery Mack, Director of the Texas Woman's University Research Institute, for her invaluable assistance and gui­ dance during the author's entire graduate program, and for help in the preparation of this dissertation; To the National Aeronautics and Space Administration for their support of the research project of which the author's study is a part; To Dr. Elsa A. Dozier for directing the author's s tucly during 1969, and to Dr. Kathryn Montgomery beginning in early 1970, for serving as the immeclia te director of the author while she was working on the completion of the investic;ation and the preparation of this dis- sertation; To Dr. Jessie Bateman, Dean of the College of Household Arts and Sciences, for her assistance in all aspects of the author's graduate program; iii To Dr. Ralph Pyke and Mr. Walter Gilchrist 1 for their ass is­ tance and generous kindness while the author's research program was in progress; To Mr. Eugene Van Hooser 1 for help during various parts of her research program; To Dr.
    [Show full text]
  • A Thesis Entitled "APPLICATIONS of GAS CHROMATOGRAPHY
    A Thesis entitled "APPLICATIONS OF GAS CHROMATOGRAPHY - MASS SPECTROMETRY IN STEROID CHEMISTRY" Submitted in part fulfilment of the requirements for admittance to the degree of Doctor of Philosophy in The University of Glasgow by T.A. Baillie, B.Sc. University of Glasgow 1973. ProQuest Number: 11017930 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11017930 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ACKNOWLEDGEMENTS I would like to express my sincere thanks to Dr. C.3.W. Brooks for his guidance and encouragement at all times, and to Professors R.A. Raphael, F.R.S., and G.W. Kirby, for the opportunity to carry out this research. Thanks are also due to my many colleagues for useful discussions, and in particular to Dr. B.S. Middleditch who was associated with me in the work described in Section 3 of this thesis. The work was carried out during the tenure of an S.R.C. Research Studentship, which is gratefully acknowledged. Finally, I would like to thank Miss 3.H.
    [Show full text]
  • Structural Basis for Human Sterol Isomerase in Cholesterol Biosynthesis and Multidrug Recognition
    ARTICLE https://doi.org/10.1038/s41467-019-10279-w OPEN Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition Tao Long 1, Abdirahman Hassan 1, Bonne M Thompson2, Jeffrey G McDonald1,2, Jiawei Wang3 & Xiaochun Li 1,4 3-β-hydroxysteroid-Δ8, Δ7-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, 1234567890():,; oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacolo- gically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. The compounds exploit their positively-charged amine group to mimic the carbocationic sterol intermediate. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. This work reveals the catalytic mechanism of EBP-mediated isomerization in cholesterol biosynthesis and how this protein may act as a multi-drug binder. 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 2 Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 3 State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. 4 Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
    [Show full text]
  • Evolution of 17Beta-Hydroxysteroid Dehydrogenases and Their Role in Androgen, Estrogen and Retinoid Action
    UC San Diego UC San Diego Previously Published Works Title Evolution of 17beta-Hydroxysteroid Dehydrogenases and Their Role in Androgen, Estrogen and Retinoid Action Permalink https://escholarship.org/uc/item/1md640v5 Journal Molecular and Cellular Endocrinology, 171 Author Baker, Michael E Publication Date 2001 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Molec ular and Cellular Endocrinol ogy vol. 171, pp. 211 -215, 2001. Evolution of 17 -Hydroxysteroid Dehydrogenases and Their Role in Androgen, Estrogen and Retinoid Action Michael E. Baker Department of Medicine, 0823 University of California, San Diego 950 0 Gilman Drive La Jolla, CA 92093 -0823 phone: 858 -534 -8317 fax: 858 -822 -0873 e-mail: [email protected] Abstract. 17 -hydroxysteroid dehydrogenases (17 -HSDs) regulate androgen and estrogen concentrations in mammals. By 1995, four distinct enzymes with 17 -HSD activity had been identified: 17 -HSD -types 1 and 3, which in vivo are NADPH -dependent reductases; 17 -HSD - types 2 and 4, which in vivo are NAD +-dependent oxidases. Since then six additional enzymes with 17 -HSD activity have been isolated from mammal s. With the exception of 17 -HSD –type 5, which belongs to the aldoketo -reductase (AKR) family, these 17 -HSDs belong to the short chain dehydrogenases/reductases (SDR) family. Several 17 -HSDs appear to be examples of convergent evolution. That is, 17 -HSD activity arose several times from different ancestors. Some 17 -HSDs share a common ancestor with retinoid oxido -reductases and have retinol dehydrogenase activity. 17 -HSD -types 2, 6 and 9 appear to have diverged from ancestral retinoid dehydrogenas es early in the evolution of deuterostomes during the Cambrian, about 540 million years ago.
    [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]
  • Steroids an Overview on 5-Reductase Inhibitors
    Steroids 75 (2010) 109–153 Contents lists available at ScienceDirect Steroids journal homepage: www.elsevier.com/locate/steroids Review An overview on 5␣-reductase inhibitors Saurabh Aggarwal a, Suresh Thareja a, Abhilasha Verma a, Tilak Raj Bhardwaj a,b, Manoj Kumar a,∗ a University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India b I. S. F College of Pharmacy, Ferozepur Road, Moga, Punjab 142001, India article info abstract Article history: Benign prostatic hyperplasia (BPH) is the noncancerous proliferation of the prostate gland associated Received 13 July 2009 with benign prostatic obstruction and lower urinary tract symptoms (LUTS) such as frequency, hesitancy, Received in revised form 9 October 2009 urgency, etc. Its prevalence increases with age affecting around 70% by the age of 70 years. High activity of Accepted 20 October 2009 5␣-reductase enzyme in humans results in excessive dihydrotestosterone levels in peripheral tissues and Available online 30 October 2009 hence suppression of androgen action by 5␣-reductase inhibitors is a logical treatment for BPH as they inhibit the conversion of testosterone to dihydrotestosterone. Finasteride (13) was the first steroidal 5␣- Keywords: reductase inhibitor approved by U.S. Food and Drug Administration (USFDA). In human it decreases the 5␣-Reductase inhibitors Androgens prostatic DHT level by 70–90% and reduces the prostatic size. Dutasteride (27) another related analogue ␣ Azasteroids has been approved in 2002. Unlike Finasteride, Dutasteride is a competitive inhibitor of both 5 -reductase Testosterone type I and type II isozymes, reduced DHT levels >90% following 1 year of oral administration. A number BPH of classes of non-steroidal inhibitors of 5␣-reductase have also been synthesized generally by removing 5␣-Dihydrotestosterone one or more rings from the azasteroidal structure or by an early non-steroidal lead (ONO-3805) (261).
    [Show full text]
  • Comparative Proteomic Study Reveals 17Β-HSD13 As a Pathogenic Protein in Nonalcoholic Fatty Liver Disease
    Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease Wen Sua,1, Yang Wangb,c,1, Xiao Jiaa,1, Wenhan Wud, Linghai Lib, Xiaodong Tiand, Sha Lia, Chunjiong Wanga, Huamin Xua, Jiaqi Caoa, Qifei Hana, Shimeng Xub,c, Yong Chenb, Yanfeng Zhonge,f, Xiaoyan Zhangg, Pingsheng Liub,2, Jan-Åke Gustafssonh,2, and Youfei Guana,g,2 aDepartment of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Peking University Health Science Center, Beijing, 100191, China; bNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; cUniversity of Chinese Academy of Sciences, Beijing, 100049, China; dDepartment of Surgery, Peking University First Hospital, Beijing, 100044, China; fDepartment of Pathology, Health Science Center and eBeijing Autopsy Center, Peking University, Beijing, 100191, China; gDepartment of Physiology, Shenzhen University Health Science Center, Shenzhen, 518060, China; and hCenter for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204 Contributed by Jan-Åke Gustafsson, June 9, 2014 (sent for review May 24, 2014; reviewed by Yu Huang, Xiong Ruan, and Tianxin Yang) Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive atherosclerosis. In addition to a monolayer of phospholipids, accumulation of lipid droplets (LDs). The aim of this study was to LDs are also covered by many proteins (12), which have been determine the function of 17β-hydroxysteroid dehydrogenase-13 considered to play an important role in the dynamic regulation of (17β-HSD13), one of our newly identified LD-associated proteins in the size and lipid contents of LDs (13). human subjects with normal liver histology and simple steatosis, in The hallmark feature of the pathogenesis of NAFLD is the NAFLD development.
    [Show full text]
  • Ames II™ Mutagenicity Assay
    Testing of estrogenic and androgenic reference compounds using 2 versions of the yeast-based YES and YAS assay Markus Kamber Xenometrix AG, Gewerbestr. 25, CH - 4123 Allschwil, Switzerland Abstract: Results: The performance of 2 commercially available kits for the detection of estrogenic and androgenic compounds was evaluated. The kits (“XenoScreen” and “XenoScreen XL”, Xenometrix AG, Proficiency Chemicals: Estrogen Agonists and Antagonists Switzerland) are based on yeast cells transfected with the human estrogen and androgen receptors, respectively (YES and YAS, Routledge and Sumpter, 1996). The tests are performed in microtiter Expected Highest tested XenoScreen XenoScreen XenoScreen XL XenoScreen XL 1) -1 -1 -1 -1 -1 plates and are able to detect both activating (agonist) and inhibiting (antagonist) activities. Hormonal Name CAS # Class response conc. (M ) EC50 (M ) EC10 (M ) EC50 (M ) EC10 (M ) Remarks activities of test substances are detected using a lacZ reporter gene construct (β-galactosidase) and the highly sensitive substrate CPRG leading to a color change in the medium from yellow to purple. Agonists The XenoScreen kit is based on the original protocol and uses an incubation time of 48 hrs, whereas Steroid 17β-Estradiol 50-28-2 positive 1.0 x 10-8 1.4 x 10-10 4.9 x 10-11 5.0 x 10-11 1.4 x 10-11 the XenoScreen XL kit is based on a modified 18-hr exposure protocol using the enzyme lyticase to Cyclic Hydrocarbon facilitate the release of the β-galactosidase from the yeast cells. Diethylstilbestrol 56-53-1 positive 2.5 x 10-8
    [Show full text]
  • By Ferdinand Durnhofer Department of Investigative Medicine, Mcgill Uni Versi Ty, Montreal
    EFFECTS OF METOPIRONE ON VARIOUS S'rEPS OF THE CHOLESTEROL ~ 1~TOSTERONE BIOSYNTHETIC SEQUENCE IN RAT TESTlCULAR PREPARATIONS. by Ferdinand Durnhofer Department of Investigative Medicine, McGill Uni versi ty, Montreal. ABSTRACT Investigation of the effects of Hetopirone on the in vitro transformation of variouB precursors of testos~erone by rat testicular preparations has shown: 1) inhibition of the side-chain cleavage of cholesterol, demonatrated by iaolation of the labeled metabolites (l~-hydroxy­ progesterone, testosterone, ~-androstane-~,17~-diol) fraB incubations 14 witn cholssterol-4- C, and by measuring liberated labeled isocaproic l4 acid in experimenta wi th cholesterol-26- C. In both types of experiments the degree of inhibition was 60 - 7'$ (Iletopirone l x 10-'M), 2) the inbibitor,y action Gf the drug is clearly dose-related, 3) the inhibition was not reversible by increasing exogenous supplementation (NADPH-generating s,ystem), 4) freezing of testicular tissue lowered overall conversion of cholesterol, without influencing the degree of 14 inhibition, 5) conversion ef pregnen010ne-4- C was inhibited by Jiletopirone (1 x 10-3M) both in the presence of a NADPH-generating system (by 20%) and NAD (by 3a;b), 6) significant inhibition Qf the 0-17 - 0-20 lyaee (Xetopirone l x lO-3M: 37%), 7) Metopirone influences the distribution pattern of reduced metabolitea of testosterone. EFFECTS OF METOPIRONE ON VARIOUS STEPS OF THE CHOLESTEROL -+ TESTOSTERONE BIOSYNTHETIC SEQUENCE Dl RAT TESTIWLAR PREPARATIONS. by Ferdinand Durnhofer &1bmi tted to the Facul ty of Gradua te Studies and Research of McGi11 University in partial fulfilment of the requirements for the degree of Master of Science.
    [Show full text]
  • Compounds of Natural Origin and Acupuncture for the Treatment of Diseases Caused by Estrogen Deficiency Abhishek Thakur 1, Subhash C
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector J Acupunct Meridian Stud 2016;9(3):109e117 Available online at www.sciencedirect.com Journal of Acupuncture and Meridian Studies journal homepage: www.jams-kpi.com REVIEW ARTICLE Compounds of Natural Origin and Acupuncture for the Treatment of Diseases Caused by Estrogen Deficiency Abhishek Thakur 1, Subhash C. Mandal 2, Sugato Banerjee 1,* 1 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, India 2 Division of Pharmacognosy, Pharmacognosy and Phytotherapy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India Available online 17 February 2016 Received: Sep 2, 2015 Abstract Revised: Jan 24, 2016 A predominant number of diseases affecting women are related to female hormones. In Accepted: Jan 28, 2016 most of the cases, these diseases are reported to be associated with menstrual problems. These diseases affect female reproductive organs such as the breast, uterus, and ovaries. KEYWORDS Estrogen is the main hormone responsible for the menstrual cycle, so irregular menstru- acupuncture; ation is primarily due to a disturbance in estrogen levels. Estrogen imbalance leads to estrogen; various pathological conditions in premenopausal women, such as endometriosis, breast natural compounds cancer, colorectal cancer, prostate cancer, poly cysts, intrahepatic cholestasis of preg- nancy, osteoporosis, cardiovascular diseases, obesity, etc. In this review, we discuss com- mon drug targets and therapeutic strategies, including acupuncture and compounds of natural origin, for the treatment of diseases caused by estrogen deficiency. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any me- dium, provided the original work is properly cited.
    [Show full text]
  • Physiological and Biochemical Aspects of 17Β-Hydroxysteroid Dehydrogenase Type 2 and 3
    Physiological and Biochemical Aspects of 17β-Hydroxysteroid Dehydrogenase Type 2 and 3 Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Roger Thomas Engeli aus Sulgen (TG), Schweiz Basel, 2017 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung-Nicht kommerziell 4.0 International Lizenz. Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Dr. Alex Odermatt und Prof. Dr. Rik Eggen Basel, den 20.06.2017 ________________________ Dekan Prof. Dr. Martin Spiess 2 Table of Contents Table of Contents ............................................................................................................................... 3 Abbreviations ..................................................................................................................................... 4 1. Summary ........................................................................................................................................ 6 2. Introduction ................................................................................................................................... 8 2.1 Steroid Hormones ............................................................................................................................... 8 2.2 Human Steroidogenesis....................................................................................................................
    [Show full text]