DOCSLIB.ORG

Male Contraception: Where Are We Going and Where Have We

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Male Contraception: Where Are We Going and Where Have We View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Edinburgh Research Explorer Edinburgh Research Explorer Male Contraception: Where are we going and where have we been? Citation for published version: Reynolds-Wright, J & Anderson, R 2019, 'Male Contraception: Where are we going and where have we been?', BMJ Sexual & Reproductive Health. https://doi.org/10.1136/bmjsrh-2019-200395 Digital Object Identifier (DOI): 10.1136/bmjsrh-2019-200395 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: BMJ Sexual & Reproductive Health General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 11. May. 2020 Review BMJ Sex Reprod Health: first published as 10.1136/bmjsrh-2019-200395 on 19 September 2019. Downloaded from Male contraception: where are we going and where have we been? John Joseph Reynolds-Wright, Richard A Anderson MRC Centre for Reproductive ABSTRACT Key messages Health, The Queen’s Medical Progress in developing new reversible male Research Institute, University of contraception has been slow. While the Edinburgh, Edinburgh, UK ► Development of male hormonal hormonal approach has been clearly shown contraception has been delayed by Correspondence to to be capable of providing effective and multiple factors, but new clinical trials Dr John Joseph Reynolds-Wright, reversible contraception, there remains no MRC Centre for Reproductive are closer than ever to bringing viable product available. Currently, trials of a self- Health, The Queen’s Medical products to market. administered gel combination of testosterone Research Institute, University ► With new technologies, new potential of Edinburgh, Edinburgh EH16 and the progestogen Nestorone® are under non-hormonal targets for male 4TJ, UK; john. reynolds- wright@ way, complementing the largely injectable nhs. net contraception have been discovered. methods previously investigated. Novel long- ► Developing a greater range of male Received 8 May 2019 acting steroids with both androgenic and methods is vital to providing holistic Revised 13 August 2019 progestogenic activity are also in early clinical reproductive healthcare. Accepted 30 August 2019 trials. The non-hormonal approach offers potential advantages, with potential sites of action on spermatogenesis, and sperm Protected by copyright. maturation in the epididymis or at the vas, but horizon and may start coming to market remains in preclinical testing. Surveys indicate the in the medium term. willingness of men, and their partners, to use a new male method, but they continue to lack that THE LIFE COURSE OF A SPERM opportunity. Spermatogenesis begins in the brain. The hypothalamus secretes gonadotro- INTRODUCTION phin-releasing hormone (GnRH), which The Faculty of Sexual and Reproduc- in turn stimulates the anterior pituitary tive Healthcare vision statement1 focuses to release luteinising hormone (LH) and on patient experience, specifically that follicle stimulating hormone (FSH). These patients should have access to the full range hormones then act on the Leydig and http://jfprhc.bmj.com/ of contraceptive options. For men, these Sertoli cells within the testis. options are currently limited to condoms Leydig cells produce testosterone, and vasectomy. Both these methods have which is secreted into the bloodstream. their positives—condoms continue to Serum testosterone supports a wide range play a vital role in infection prevention of male functions and is a key compo- and are a widely used, easily accessible nent of the negative feedback loop that method of contraception; likewise, vasec- controls GnRH and gonadotrophin on October 10, 2019 at University of Edinburgh. tomy is a highly effective permanent production. Testicular levels of testos- method of contraception. However, they terone are approximately 40 times higher 2 are not sufficient for many sexually active than in blood and support Sertoli cells in men who wish to have control over their their role in spermatogenesis. © Author(s) (or their fertility, and for their partners who wish After release from Sertoli cells (‘spermi- employer(s)) 2019. Re-use to share the burden of contraception. We ation’), sperm progress through the semi- permitted under CC BY. know that sterilisation and condoms are niferous tubules and into the epididymis Published by BMJ. not sufficient for women to control their for storage, concentration and maturation To cite: Reynolds-Wright JJ, fertility, and having a greater breadth of to functional sperm. Finally, at the point Anderson RA. BMJ Sex Reprod of ejaculation, sperm are transferred Health Published Online First: contraceptive tools allows more couples [please include Day Month to have better reproductive control. This from the epididymis via the vas deferens Year]. doi:10.1136/ review will help clinicians to understand to the urethra and then out of the body bmjsrh-2019-200395 the male contraceptives that are on the (figure 1). Reynolds-Wright JJ, Anderson RA. BMJ Sex Reprod Health 2019;0:1–7. doi:10.1136/bmjsrh-2019-200395 1 Review BMJ Sex Reprod Health: first published as 10.1136/bmjsrh-2019-200395 on 19 September 2019. Downloaded from history of male contraception will hopefully answer this question. The quest to develop new forms of male contracep- tion started at more or less the same time as the devel- opment of female hormonal contraceptive methods, but has taken a very different course. The culture shift that took place in the wake of the phenomenon of the hormonal contraceptive pill for women3 in 1965 led to the creation of the WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO-HRP).3 Within the WHO-HRP a task force for developing methods of male fertility regulation was developed. This iden- tified possible modalities for male contraceptives through basic science research projects and multi- centre landmark clinical trials of testosterone alone and in combination with progestogens.3 The task force also focused efforts on the development and promo- tion of no-scalpel vasectomy, which has become the predominant technique globally, and gossypol, which was planned as a reversible contraceptive but unfortu- nately had to be abandoned due to issues with toxicity and irreversibility.3 Over approximately a decade from the mid-1980s, the task force developed new esters of testosterone with the hope that they would be developed by Protected by copyright. industry partners for use in treatment of hypogo- Figure 1 The hypothalamic-pituitary-testicular axis and its role in nadal patients and as male contraceptives. However, spermatogenesis. CCBY 4.0 Licence – John Reynolds-Wright. Image this did not come to fruition, for reasons including accessible via https://flic.kr/p/2hgvk5V6A. FSH, follicle stimulating concerns in industry about security of patents, possi- hormone; GnRH, gonadotrophin-releasing hormone; LH, luteinising bility of litigation, perception of a ‘small market’ and hormone. competition with their existing female contraceptives. Nevertheless, landmark contraceptive efficacy studies Potential novel male contraceptives can be divided were conducted at this time using weekly injections of into those based on a hormonal approach, acting testosterone enanthate. The first of these demonstrated via gonadotrophin suppression, and non-hormonal that most men (70%) became azoospermic when administered 200 mg/week of testosterone enanthate, methods. Hormonal strategies for male contracep- http://jfprhc.bmj.com/ tion involve the hypothalamic-pituitary-testicular and couples then used this as their exclusive method (HPT) axis, using exogenous testosterone in combina- of contraception for 12 months. This proved to be a highly effective contraceptive, with only 0.8 pregnan- tion with progestogen to drive the negative feedback 4 response and suppress GnRH, FSH and LH. Exoge- cies per 100 person-years of exposure. A second study nous replacement of testosterone prevents hypogo- extended this to ask ‘how low does a sperm count nadal side effects from HPT axis suppression but is not need to go?’, and used 3 million/mL as the cut-off for entry to the efficacy phase. This increased the response delivered at high enough concentrations to support on October 10, 2019 at University of Edinburgh. spermatogenesis directly. Non-hormonal methods can rate (92% of men achieved sperm counts below this act at any point during spermatogenesis or can target threshold and entered the efficacy phase), and again excellent efficacy was demonstrated with a Pearl Index sperm maturation, detachment, motility or transport 5 out of the testis. This includes physical methods of of 1.4 (95% CI 0.4 to 3.7). Although a Pearl Index infiltration of the vas with a dissolvable compound to of 8.1 (95% CI 2.2 to 20.7) was achieved even in block or damage sperm during their movement along
Load more

Recommended publications
  • In Vitro Testicular Toxicity Models : Opportunities for Advancement Via Biomedical Engineering Techniques
    Erschienen in: Alternatives to Animal Experimentation : ALTEX ; 30 (2013), 3. - S. 353-377 http://dx.doi.org/10.14573/altex.2013.3.353 t4 Report* In Vitro Testicular Toxicity Models: Opportunities for Advancement via Biomedical Engineering Techniques Louise Parks Saldutti 1, Bruce K. Beyer 2, William Breslin 3, Terry R. Brown 4, Robert E. Chapin 5, Sarah Campion 5, Brian Enright 6, Elaine Faustman 7, Paul M. D. Foster 8, Thomas Hartung 9, William Kelce 10, James H. Kim 11, Elizabeth G. Loboa 12, Aldert H. Piersma 13, David Seyler 14, Katie J. Turner 15, Hanry Yu 16, Xiaozhong Yu 17, and Jennifer C. Sasaki 18 1 2 Department of Development & Reproduction, Merck & Co., West Point, PA, USA; Department of Disposition, Safety 3 and Animal Research – Preclinical Safety, Sanofi U.S. Inc., Bridgewater, NJ, USA; Eli Lilly and Company, Lilly Research 4 Laboratories, Indianapolis, IN, USA; Department of Biochemistry & Molecular Biology, Johns Hopkins Bloomberg School of 5 Public Health, Baltimore, MD, USA; Pfizer Inc., Global R&D, Developmental and Reproductive Toxicology Group, Groton, 7 CT, USA; 6AbbVie Inc., North Chicago, IL, USA; University of Washington, Department of Environmental and Occupational 8 Health Sciences, Institute for Risk Analysis and Risk Communication, Seattle, WA, USA; National Toxicology Program, National Institutes of Environmental Health Sciences, National Institute of Health, Department of Health and Human Services, 9 Research Triangle Park, NC, USA; Johns Hopkins University, Bloomberg School of Public Health, Center for
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2015/0202317 A1 Rau Et Al
    US 20150202317A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0202317 A1 Rau et al. (43) Pub. Date: Jul. 23, 2015 (54) DIPEPTDE-BASED PRODRUG LINKERS Publication Classification FOR ALPHATIC AMNE-CONTAINING DRUGS (51) Int. Cl. A647/48 (2006.01) (71) Applicant: Ascendis Pharma A/S, Hellerup (DK) A638/26 (2006.01) A6M5/9 (2006.01) (72) Inventors: Harald Rau, Heidelberg (DE); Torben A 6LX3/553 (2006.01) Le?mann, Neustadt an der Weinstrasse (52) U.S. Cl. (DE) CPC ......... A61K 47/48338 (2013.01); A61 K3I/553 (2013.01); A61 K38/26 (2013.01); A61 K (21) Appl. No.: 14/674,928 47/48215 (2013.01); A61M 5/19 (2013.01) (22) Filed: Mar. 31, 2015 (57) ABSTRACT The present invention relates to a prodrug or a pharmaceuti Related U.S. Application Data cally acceptable salt thereof, comprising a drug linker conju (63) Continuation of application No. 13/574,092, filed on gate D-L, wherein D being a biologically active moiety con Oct. 15, 2012, filed as application No. PCT/EP2011/ taining an aliphatic amine group is conjugated to one or more 050821 on Jan. 21, 2011. polymeric carriers via dipeptide-containing linkers L. Such carrier-linked prodrugs achieve drug releases with therapeu (30) Foreign Application Priority Data tically useful half-lives. The invention also relates to pharma ceutical compositions comprising said prodrugs and their use Jan. 22, 2010 (EP) ................................ 10 151564.1 as medicaments. US 2015/0202317 A1 Jul. 23, 2015 DIPEPTDE-BASED PRODRUG LINKERS 0007 Alternatively, the drugs may be conjugated to a car FOR ALPHATIC AMNE-CONTAINING rier through permanent covalent bonds.
    [Show full text]
  • Metabolic Enzyme/Protease
    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Metabolic Enzyme/Protease Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions.
    [Show full text]
  • Abstracts 2019 Focus Sessions
    52nd ANNUAL CONFERENCE Beyond Possible: Remarkable Transformation of Reproductive Biology Abstracts 2019 Focus Sessions S1.1 - The maternal lactocrine continuum programming uterine capacity. Frank Bartol, Jeffrey Vallet, Carol Bagnell Lactocrine signaling describes a mechanism by which milk-borne bioactive factors (MbFs) are communicated from mother to offspring by consequence of nursing. Lactocrine communication is an element of the maternal environmental continuum of factors that define pre- and postnatal developmental conditions and, therefore, the trajectory of mammalian development and offspring phenotype. Lactocrine-active factors can include MbFs of maternal origin, as well as factors of environmental origin to which the lactating female is exposed. Ideally, lactocrine signals communicated to nursing offspring insure a smooth transition and adaptation to extrauterine life. Disruption of lactocrine communication occurs when the quality or quantity of colostrum (first milk) is compromised. This can have lasting consequences for the health and fitness of nursing young. In the pig (Sus domesticus), imposition of a lactocrine-null state from birth (postnatal day = PND 0) by feeding milk replacer altered global patterns of uterine gene expression by PND 2, and inhibited endometrial development by PND 14. Similarly, lactocrine deficiency, reflecting minimal colostrum consumption from birth, retarded endometrial development in neonates, altered endometrial gene expression on pregnancy day (PxD) 13, and reduced live litter size in adult, neonatally lactocrine-deficient gilts. Elements of the lactocrine-sensitive, adult endometrial transcriptome at PxD 13 included factors affecting conceptus-endometrial interactions. A window for lactocrine programming of porcine endometrial function and uterine capacity was defined during the first 24 h of postnatal life. Lactocrine effects on the neonatal uterine miRNA-mRNA interactome at PND 2 implicated miRNAs as elements of the maternal lactocrine programming mechanism.
    [Show full text]
  • EUT Congress News 32Nd Annual Congress of the European Association of Urology Sunday, 26 March 2017 London, 24-28 March 2017
    Second Edition European Urology Today EUT Congress News 32nd Annual Congress of the European Association of Urology Sunday, 26 March 2017 London, 24-28 March 2017 Hurdles in managing renal cancer EAU strengthens ‘Sleepless Nights’ session offers insights on legal pitfalls ties across borders By Erika de Groot By Joel Vega dock’ as he presented his arguments for performing a renal tumour biopsy (RTB). Leigh, who specializes The EAU’s engagement with the European Union Insights into the legal pitfalls and challenges of in medical negligence, pressed Bex on his rationale (EU), the different EAU Offices’ new projects, and the offering balanced and optimal treatments to kidney for RTB, to which Bex conceded that there are no announcement of newly elected officers topped the cancer patients were explored and debated in reliable approaches for diagnosing an oncocytoma agenda yesterday at the annual General Assembly. Plenary Session 1, a newly introduced format where before surgery. a legal veteran subjected three urologists to intense EAU Members cross-examination regarding their surgical strategies. Leigh emphasized that despite the low statistics on As of March 2017, there are a total of 15,409 EAU risks and complications, patients view the matter in members, the majority of whom are active members In a well-attended and applauded session, expert an altogether different way. The loss of a kidney or (7,397), alongside 3,608 junior members, 2,441 active medical litigation lawyer Bertie Leigh (GB) put suffering the consequences of complications is international members, and 531 junior international Professors Alex Bex (NL), Karim Bensalah (FR) and traumatic for patients.
    [Show full text]
  • UCC Library and UCC Researchers Have Made This Item Openly Available. Please Let Us Know How This Has Helped You. Thanks! Downlo
    UCC Library and UCC researchers have made this item openly available. Please let us know how this has helped you. Thanks! Title The application of aryne chemistry and use of α-diazo carbonyl derivatives in indazole synthesis with biological evaluation Author(s) Hanlon, Patricia M. Publication date 2016 Original citation Hanlon, P.M. 2016. The application of aryne chemistry and use of α- diazo carbonyl derivatives in indazole synthesis with biological evaluation. PhD Thesis, University College Cork. Type of publication Doctoral thesis Rights © 2016, Patricia M. Hanlon. http://creativecommons.org/licenses/by-nc-nd/3.0/ Item downloaded http://hdl.handle.net/10468/2546 from Downloaded on 2021-10-08T13:09:14Z THE APPLICATION OF ARYNE CHEMISTRY AND USE OF α-DIAZO CARBONYL DERIVATIVES IN INDAZOLE SYNTHESIS WITH BIOLOGICAL EVALUATION Patricia M. Hanlon, B.Sc. A thesis presented for the degree of Doctor of Philosophy to THE NATIONAL UNIVERSITY OF IRELAND, CORK Department of Chemistry University College Cork Supervisor: Dr. Stuart G. Collins Head of Department: Prof. Justin D. Holmes January 2016 Table of Chapters Acknowledgements iv Abstract vi Table of Abbreviations viii Table of Figures xv Chapter 1 Introduction 1 Chapter 2 Results and Discussion 59 Chapter 3 Experimental 226 Appendix I NCI-60 One-Dose Mean Graphs i ii DECLARATION BY CANDIDATE I hereby confirm that the body of work described within this thesis for the degree of Doctor of Philosophy, is my own research work, and has not been submitted for any other degree, either in University College Cork or elsewhere. All external references and sources are clearly acknowledged and identified within the contents.
    [Show full text]
  • The Application of Aryne Chemistry and Use of Α-Diazo Carbonyl Derivatives in Indazole Synthesis with Biological Evaluation
    UCC Library and UCC researchers have made this item openly available. Please let us know how this has helped you. Thanks! Title The application of aryne chemistry and use of α-diazo carbonyl derivatives in indazole synthesis with biological evaluation Author(s) Hanlon, Patricia M. Publication date 2016 Original citation Hanlon, P.M. 2016. The application of aryne chemistry and use of α- diazo carbonyl derivatives in indazole synthesis with biological evaluation. PhD Thesis, University College Cork. Type of publication Doctoral thesis Rights © 2016, Patricia M. Hanlon. http://creativecommons.org/licenses/by-nc-nd/3.0/ Item downloaded http://hdl.handle.net/10468/2546 from Downloaded on 2021-10-04T19:07:46Z THE APPLICATION OF ARYNE CHEMISTRY AND USE OF α-DIAZO CARBONYL DERIVATIVES IN INDAZOLE SYNTHESIS WITH BIOLOGICAL EVALUATION Patricia M. Hanlon, B.Sc. A thesis presented for the degree of Doctor of Philosophy to THE NATIONAL UNIVERSITY OF IRELAND, CORK Department of Chemistry University College Cork Supervisor: Dr. Stuart G. Collins Head of Department: Prof. Justin D. Holmes January 2016 Table of Chapters Acknowledgements iv Abstract vi Table of Abbreviations viii Table of Figures xv Chapter 1 Introduction 1 Chapter 2 Results and Discussion 59 Chapter 3 Experimental 226 Appendix I NCI-60 One-Dose Mean Graphs i ii DECLARATION BY CANDIDATE I hereby confirm that the body of work described within this thesis for the degree of Doctor of Philosophy, is my own research work, and has not been submitted for any other degree, either in University College Cork or elsewhere. All external references and sources are clearly acknowledged and identified within the contents.
    [Show full text]
  • Bioactive Molecules • Building Blocks • Intermediates
    • Bioactive Molecules • Building Blocks • Intermediates www.ChemScene.com Anti-Cancer Compound Library (96-well) Product Details: Catalog Number: CS-L025 Formulation: A collection of 4779 anti-cancer compounds supplied as pre-dissolved Solutions or Solid Container: 96- or 384-well Plate with Peelable Foil Seal; 96-well Format Sample Storage Tube With Screw Cap and Optional 2D Barcode Storage: -80°C Shipping: Blue ice Packaging: Inert gas Plate layout: CS-L025-1 1 2 3 4 5 6 7 8 9 10 11 12 SKF-96365 Fumarate MRT68921 a Empty (hydrochlorid ML162 ML-210 hydratase-IN- (dihydrochlori Peretinoin SR-3029 CBR-5884 Mivebresib AZD0156 Empty e) 1 de) HLCL-61 b Empty BAY-876 BAY1125976 BAY-1436032 Tomivosertib LY3177833 (hydrochlorid PQR620 AT-130 NSC 663284 MK-4101 Empty e) Flavopiridol c Empty Flavopiridol (Hydrochlorid SNS-032 Ko 143 KNK437 TA-02 Mitoquinone AZD-5438 R547 4-IBP Empty e) (mesylate) d Empty SAR-020106 HUHS015 SMER28 A-196 TPEN CP21R7 HC-067047 EAI045 RSL3 GSK6853 Empty IQ-1S (free Rho-Kinase- e Empty CZ415 SANT-1 ME0328 acid) GSK591 Madrasin SZL P1-41 IN-1 Nutlin-3a 9-amino-CPT Empty MELK-8a f Empty GNE-495 EPI-001 CA-074 BI-7273 BI-9564 CL-82198 MS049 Remetinostat (hydrochlorid MRK-016 Empty methyl ester e) SHP099 g Empty Nigericin BH3I-1 SHP099 (hydrochlorid (S)- NVP- F16 PF-04979064 Nevanimibe CFMTI Empty (sodium salt) e) ML753286 BAW2881 hydrochloride h Empty Ro 67-7476 GNF-6231 PHCCC FCCP Linaprazan UKI-1 BFH772 CPI-455 KDM5-IN-1 CAN508 Empty Plate layout: CS-L025-2 1 2 3 4 5 6 7 8 9 10 11 12 αvβ1 integrin- TM5275 a Empty CCF642
    [Show full text]
  • Title Cytokines and Junction Restructuring During Spermatogenesis
    CORE Metadata, citation and similar papers at core.ac.uk Provided by HKU Scholars Hub Cytokines and junction restructuring during spermatogenesis - Title A lesson to learn from the testis Author(s) Xia, W; Mruk, DD; Lee, WM; Cheng, CY Cytokine And Growth Factor Reviews, 2005, v. 16 n. 4-5, p. 469- Citation 493 Issued Date 2005 URL http://hdl.handle.net/10722/84892 Rights Cytokine & Growth Factor Reviews. Copyright © Elsevier Ltd. DTD 5 This is a pre-published version Cytokine & Growth Factor Reviews xxx (2005) xxx–xxx 1 www.elsevier.com/locate/cytogfr 2 Cytokines and junction restructuring during spermatogenesis—a lesson 3 to learn from the testis 4 Weiliang Xia, Dolores D. Mruk, Will M. Lee, C. Yan Cheng * 5 Population Council, Center for Biomedical Research, 1230 York Avenue, New York, NY 10021, USA 6 87 9 Abstract 10 In the mammalian testis, preleptotene and leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must 11 traverse the blood-testis barrier (BTB) during spermatogenesis, entering the adluminal compartment for further development. However, until 12 recently the regulatory mechanisms that regulate BTB dynamics remained largely unknown. We provide a critical review regarding the 13 significance of cytokines in regulating the ‘opening’ and ‘closing’ of the BTB. We also discuss how cytokines may be working in concert with 14 adaptors that selectively govern the downstream signaling pathways. This process, in turn, regulates the dynamics of either Sertoli–Sertoli 15 tight junction (TJ), Sertoli–germ cell adherens junction (AJ), or both junction types in the epithelium, thereby permitting TJ opening without 16 compromising AJs, and vice versa.
    [Show full text]
  • Membrane Transporter/Ion Channel
    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Membrane Transporter/Ion Channel Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, binding with small molecules in extracellular space, the recognition process in the immune system, energy transduction, osmoregulation, and physiological and developmental processes. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. ATP-powered pumps are ATPases that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against a chemical concentration gradient or electric potential. Channel proteins transport water or specific types of ions down their concentration or electric potential gradients. Many other types of channel proteins are usually closed, and open only in response to specific signals. Because these types of ion channels play a fundamental role in the functioning of nerve cells. Transporters, a third class of membrane transport proteins, move a wide variety of ions and molecules across cell membranes. Membrane transporters either enhance or restrict drug distribution to the target organs. Depending on their main function, these membrane transporters are divided into two categories: the efflux (export) and the influx (uptake) transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system ion channels have been linked to many diseases such, but not limited to, ataxias, paralyses, epilepsies, and deafness indicative of the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information.
    [Show full text]
  • 1-S2.0-S2214854X20300121-Main
    Institutional Repository - Research Portal Dépôt Institutionnel - Portail de la Recherche University of Namurresearchportal.unamur.be RESEARCH OUTPUTS / RÉSULTATS DE RECHERCHE The human testes Hussain, Aatif; Gilloteaux, Jacques Published in: Translational Research in Anatomy DOI: Author(s)10.1016/j.tria.2020.100073 - Auteur(s) : Publication date: 2020 Document Version PublicationPublisher's date PDF, - also Date known de aspublication Version of record : Link to publication Citation for pulished version (HARVARD): Hussain, A & Gilloteaux, J 2020, 'The human testes: Estrogen and ageing outlooks', Translational Research in PermanentAnatomy ,link vol. 20,- Permalien 100073. https://doi.org/10.1016/j.tria.2020.100073 : Rights / License - Licence de droit d’auteur : General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate
    [Show full text]
  • Houlutuulitu N
    HOULUTUULITUUS009789120B2 (12 ) United States Patent (10 ) Patent No. : US 9 ,789 , 120 B2 Bradner et al. (45 ) Date of Patent: Oct. 17 , 2017 ( 54 ) MALE CONTRACEPTIVE COMPOSITIONS 5 ,593 ,988 A 1/ 1997 Tahara et al . AND METHODS OF USE 5 ,712 ,274 A * 1 / 1998 Sueoka . .. .. C07D 495 / 14 514 / 219 5 ,721 , 231 A 2 / 1998 Moriwaki et al. Ê(71 ) Applicants :Dana - Farber Cancer Institute , Inc . , 5 ,753 ,649 A 5 / 1998 Tahara et al. Boston , MA (US ) ; Baylor College of 5 ,760 ,032 A 6 / 1998 Kitajima et al . Medicine, Houston , TX (US ) 5 , 846 , 972 A 12 / 1998 Buckman et al . 5 ,854 ,238 A 12 / 1998 Kempen 6 , 444 , 664 B1 9 / 2002 Princen et al . (72 ) Inventors : James Elliott Bradner , Cambridge , 6 ,861 , 422 B2 3 / 2005 Hoffmann et al . MA (US ) ; Martin Matzuk , Houston , 7 , 015 , 213 B1 3 / 2006 Bigg et al. TX (US ) ; Jun Qi, Sharon , MA (US ) 7 , 528, 143 B2 5 / 2009 Noronha et al. 7 , 528, 153 B2 5 /2009 Noronha et al. ( 73 ) Assignees: Dana - Farber Cancer Institute , Inc. , 7 , 589 , 167 B2 9 /2009 Zhou et al . Boston , MA (US ) ; Baylor College of NNNN7 ,750 , 152 B2 7 / 2010 Hoffman et al. 7 ,786 , 299 B2 8 / 2010 Hoffman et al . Medicine , Houston , TX (US ) 7 , 816, 530 B2 10 / 2010 Grauert 7 , 825 , 246 B2 11/ 2010 Noronha et al . ( * ) Notice : Subject to any disclaimer , the term of this 8 ,003 ,786 B28 / 2011 Hoffman et al . patent is extended or adjusted under 35 8 ,044 ,042 B2 * 10 / 2011 Adachi .
    [Show full text]