DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2010/0061976 A1 Ishikawa Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2010/0061976 A1 Ishikawa Et Al US 20100061976A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0061976 A1 Ishikawa et al. (43) Pub. Date: Mar. 11, 2010 (54) METHOD FORTREATING OR PREVENTING Related U.S. Application Data OSTEOPOROSS BY REDUCING FOLLCLE (63) Continuation-in-part of application No. 12/220,708, STMULATING HORMONE TO CYCLC filed on Jul. 24, 2008, Continuation-in-part of applica PHYSIOLOGICAL LEVELS INA tion No. 12/220,704, filed on Jul. 24, 2008, Continua MAMMALLAN SUBJECT tion-in-part of application No. 12/220,707, filed on Jul. 24, 2008, Continuation-in-part of application No. (75) Inventors: Muriel Y. Ishikawa, Livermore, 12/455,272, filed on May 29, 2009. CA (US); Lowell L. Wood, JR. Publication Classification Bellevue, WA (US) (51) Int. Cl. A 6LX 39/395 (2006.01) Correspondence Address: A638/00 (2006.01) SEARETE LLC A63L/7088 (2006.01) CLARENCET. TEGREENE A6II 3/56 (2006.01) 1756 - 114THAVE., S.E., SUTE 110 (52) U.S. Cl. .......... 424/130.1: 514/2: 514/44 R: 514/169 BELLEVUE, WA 98004 (US) (57) ABSTRACT A method is described for treating or preventing a bone loss (73) Assignee: Searete LLC, a limited liability disease or a bone loss disorder in a mammalian Subject or corporation of the State of reducing the incidence of a bone loss disease or a bone loss Delaware disorder or alleviating the symptoms thereof. The method includes providing to the mammalian Subject at least one treatment regimen including at least one follicle-stimulating (21) Appl. No.: 12/462,057 hormone modulator configured to and in an amount Sufficient to reduce bioactivity or bioavailability of follicle-stimulating (22) Filed: Jul. 27, 2009 hormone in the mammalian Subject. Patent Application Publication Mar. 11, 2010 Sheet 1 of 3 US 2010/0061976 A1 Subject #1 FIGURE 1 Perimenopausal or postmenopausal female subject: Prior to Treatment Follicle-stimulating Luteinizing Level Level Pituitary Hormone Cycle 400 Estrogen Proges Level 200 terOne 100 Level Sex Hormone Cycle Subject #1 Perimenopausal or postmenopausal female subject: Following Treatment Follicle-stimulating Luteinizing hormone :- hormone FSH LH Level Level Pituitary Hormone Cycle 400 Proges Estrogen roges Level 200 terOc Level 1 OO 4. 8 12 15 18 22 28 Day of Cycle Patent Application Publication Mar. 11, 2010 Sheet 2 of 3 US 2010/0061976 A1 FIGURE 2 (son200 2O2 N- (204 206 Directly measure Obtain data on hormone Directly measure & record hormone levels of the subject from & record hormone levels in the subject medical history e.g., provided by GP to levels in the subject specialist 208 Obtain data regarding premenopausal hormone levels; e.g., Obtain data regarding cyclic changes, age-related changes current hormone levels Determine treatment regimen e.g., using computational methods, comparisons, etc. Provide treatment regimen to the subject Monitor current levels in the subject Patent Application Publication Mar. 11, 2010 Sheet 3 of 3 US 2010/0061976 A1 FIGURE 3 300 A system 301 a sensor configured to detect one or more hormones in one or more tissues of the mammalian subject; and 302 a controller in communication with the sensor, wherein the controller is configured to provide at least one treatment regimen including at least one follicle-stimulating hormone modulator configured to and in an amount sufficient to reduce bioactivity or bioavailability of follicle stimulating hormone in the mammalian subject, and to approximate the level of bioactive or bioavailable follicle-stimulating hormone to a target cyclic physiological pre-disease effective level in the mammalian subject. 303 304 305 306 wherein the at least wherein the at least wherein the at least wherein the at least One treatment One treatment One treatment One treatment regimen further regimen is regimen is regimen is includes providing determined based on determined based on determined based replacement therapy population data of pre-disease cyclic on pre-disease including one or physiological cyclic levels of steroid cyclic levels of more steroid pre-disease levels of hormone in the follicle-stimulating hormones or the one or more mammalian subject hormone in the metabolites or steroid hormones in and on current cyclic mammalian subject Ole O Ore levels of steroid and on current modulators thereof. mammalian subjects. hormone in the cyclic levels of mammalian subject. follicle-stimulating hormone in the mammalian subject. US 2010/006 1976 A1 Mar. 11, 2010 METHOD FOR TREATING OR PREVENTING OR CONDITION UTILIZING ESTROGEN RECEP OSTEOPOROSS BY REDUCING FOLLCLE TOR MODULATORS BASED ON APOE ALLELIC STMULATING. HORMONE TO CYCLC PROFILE OF A MAMMALIAN SUBJECT, naming PHYSIOLOGICAL LEVELS INA Roderick A. Hyde, Muriel Y. Ishikawa, Eric C. MAMMALIAN SUBJECT Leuthardt, Dennis J. Rivet, Elizabeth A. Sweeney, Low ell L. Wood, Jr. and Victoria Y. H. Wood as inventors, CROSS-REFERENCE TO RELATED filed 29 May 2009, which is currently co-pending, or is APPLICATIONS an application of which a currently co-pending applica tion is entitled to the benefit of the filing date. 0001. The present application is related to and claims the 0006. The United States Patent Office (USPTO) has pub benefit of the earliest available effective filing date(s) from lished a notice to the effect that the USPTO's computer pro the following listed application(s) (the “Related Applica grams require that patent applicants reference both a serial tions”) (e.g., claims earliest available priority dates for other number and indicate whether an application is a continuation than provisional patent applications or claims benefits under or continuation-in-part. Stephen G. Kunin, Benefit of Prior 35 USC S119(e) for provisional patent applications, for any Filed Application, USPTO Official Gazette Mar. 18, 2003, and all parent, grandparent, great-grandparent, etc. applica available at http://www.uspto.gov/web/offices/com/sol/og/ tions of the Related Application(s)). All subject matter of the 2003/week 1 1/patbene.htm. The present Applicant Entity Related Applications and of any and all parent, grandparent, (hereinafter Applicant”) has provided above a specific ref great-grandparent, etc. applications of the Related Applica erence to the application(s) from which priority is being tions is incorporated herein by reference to the extent such claimed as recited by statute. Applicant understands that the Subject matter is not inconsistent herewith. statute is unambiguous in its specific reference language and does not require either a serial number or any characteriza RELATED APPLICATIONS tion, Such as "continuation' or “continuation-in-part for 0002 For purposes of the USPTO extra-statutory claiming priority to U.S. patent applications. Notwithstand requirements, the present application constitutes a con ing the foregoing, Applicant understands that the USPTO's tinuation-in-part of U.S. patent application Ser. No. computer programs have certain data entry requirements, and 12/220,708, entitled METHOD, DEVICE, AND KIT hence Applicant is designating the present application as a FOR MAINTAINING PHYSIOLOGICAL LEVELS continuation-in-part of its parent applications as set forth OF STEROID HORMONE IN A SUBJECT, naming above, but expressly points out that such designations are not Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, to be construed in any way as any type of commentary and/or Elizabeth A. Sweeney, Lowell L. Wood, Jr. and Victoria admission as to whether or not the present application con Y. H. Wood as inventors, filed 24 Jul. 2008, which is tains any new matter in addition to the matter of its parent currently co-pending, or is an application of which a application(s). currently co-pending application is entitled to the benefit of the filing date. SUMMARY 0003 For purposes of the USPTO extra-statutory 0007. A method is described herein for treating or prevent requirements, the present application constitutes a con ing a bone loss disease or a bone loss disorderina mammalian tinuation-in-part of U.S. patent application Ser. No. Subject or reducing the incidence of a bone loss disease or a 12/220,704, entitled METHOD, DEVICE, AND KIT bone loss disorder or alleviating the symptoms thereof. The FOR MAINTAINING PHYSIOLOGICAL LEVELS method includes providing to the mammalian Subject at least OF STEROID HORMONE IN A SUBJECT, naming one treatment regimen including at least one follicle-stimu Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, lating hormone modulator configured to and in an amount Elizabeth A. Sweeney, Lowell L. Wood, Jr. and Victoria sufficient to reduce bioactivity or bioavailability of follicle Y. H. Wood as inventors, filed 24 Jul. 2008, which is stimulating hormone in the mammalian Subject. The at least currently co-pending, or is an application of which a one treatment regimen is configured to approximate the level currently co-pending application is entitled to the benefit of bioactive or bioavailable follicle-stimulating hormone to a of the filing date. target cyclic physiological pre-disease effective level in the 0004 For purposes of the USPTO extra-statutory mammalian Subject. The at least one follicle-stimulating hor requirements, the present application constitutes a con mone modulator includes, but is not limited to, an inhibitor of tinuation-in-part of U.S. patent application Ser. No. follicle-stimulating hormone bioactivity, a follicle-stimulat 12/220,707, entitled SYSTEM AND DEVICE FOR ing hormone receptor antagonist, oran inhibitor of osteoclast MAINTAINING PHYSIOLOGICAL LEVELS OF activity. The at least one treatment regimen can be determined STEROID HORMONE IN A SUBJECT, naming Rod based on pre-disease cyclic levels of follicle-stimulating hor erick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, mone in the mammalian Subject and on current cyclic levels Elizabeth A. Sweeney, Lowell L. Wood, Jr. and Victoria of follicle-stimulating hormone in the mammalian Subject. Y. H. Wood as inventors, filed 24 Jul. 2008, which is The method which includes providing the at least one treat currently co-pending, or is an application of which a ment regimen can further include providing a cyclic treatment currently co-pending application is entitled to the benefit regimen including at least one gonadotropin-releasing hor of the filing date.
Load more

Recommended publications
  • Kisspeptin and Testicular Function—Is It Necessary?
    International Journal of Molecular Sciences Review Kisspeptin and Testicular Function—Is It Necessary? Aditi Sharma 1 , Thilipan Thaventhiran 1, Suks Minhas 2, Waljit S. Dhillo 1 and Channa N. Jayasena 1,* 1 Section of Investigative Medicine, Imperial College, 6th Floor, Commonwealth Building, Hammersmith Hospital, 150 Du Cane Road, London W12 0NN, UK; [email protected] (A.S.); [email protected] (T.T.); [email protected] (W.S.D.) 2 Department of Urology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, Hammersmith, London W6 8RF, UK; [email protected] * Correspondence: [email protected] Received: 12 March 2020; Accepted: 21 April 2020; Published: 22 April 2020 Abstract: The role of kisspeptin in stimulating hypothalamic GnRH is undisputed. However, the role of kisspeptin signaling in testicular function is less clear. The testes are essential for male reproduction through their functions of spermatogenesis and steroidogenesis. Our review focused on the current literature investigating the distribution, regulation and effects of kisspeptin and its receptor (KISS1/KISS1R) within the testes of species studied to date. There is substantial evidence of localised KISS1/KISS1R expression and peptide distribution in the testes. However, variability is observed in the testicular cell types expressing KISS1/KISS1R. Evidence is presented for modulation of steroidogenesis and sperm function by kisspeptin signaling. However, the physiological importance of such effects, and whether these are paracrine or endocrine manifestations, remain unclear. Keywords: kisspeptin; kisspeptin receptor; spermatozoa; Leydig cells; Sertoli cells; testes; testosterone; LH; FSH; spermatogenesis 1. Introduction Kisspeptin is an established regulator of puberty onset [1,2], sexual maturation and adult reproductive activity [3].
    [Show full text]
  • LHRH) Antagonist Cetrorelix and LHRH Agonist Triptorelin on the Gene Expression of Pituitary LHRH Receptors in Rats
    Comparison of mechanisms of action of luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression of pituitary LHRH receptors in rats Magdolna Kovacs*†‡ and Andrew V. Schally*†§ *Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112; and †Section of Experimental Medicine, Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112 Contributed by Andrew V. Schally, August 21, 2001 The mechanisms through which luteinizing hormone (LH)-releasing however, are different. LHRH agonists achieve the inhibition of hormone (LHRH) antagonists suppress pituitary gonadotroph func- gonadotropin secretion after a period of continuous exposure (1, tions and LHRH-receptor (LHRH-R) expression are incompletely un- 2, 11–14). In contrast, antagonists of LHRH produce a compet- derstood. Consequently, we investigated the direct effect of LHRH itive blockade of LHRH-R and cause an immediate cessation of antagonist cetrorelix in vitro on the expression of the pituitary the release of gonadotropins and sex steroids, reducing the time LHRH-R gene and its ability to counteract the exogenous LHRH and of the onset of therapeutic effects as compared with the agonists the agonist triptorelin in the regulation of this gene. We also com- (1, 2, 15–17). LHRH agonists such as triptorelin, leuprolide, pared the effects of chronic administration of cetrorelix and triptore- buserelin, or goserelin (1, 2, 14) have been used worldwide for lin on the LHRH-R mRNA level and gonadotropin secretion in ovari- nearly two decades, but LHRH antagonists such as cetrorelix, ectomized (OVX) and normal female rats. The exposure of pituitary ganirelix, and Abarelix have been introduced into the clinical cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM triptorelin for 5 h practice relatively recently (1, 2, 15, 16).
    [Show full text]
  • Personalized ADT
    Personalized ADT Thomas Keane MD Conflicts • Ferring • Tolemar • Bayer • Astellas • myriad Personalized ADT for the Specific Paent • Cardiac • OBesity and testosterone • Fsh • High volume metastac disease • Docetaxol • Significant LUTS Cardiovascular risk profile and ADT Is there a difference? Degarelix Belongs to a class of synthe@c drug, GnRH antagonist (Blocker) GnRH pGlu His Trp Ser Tyr Gly Leu Arg Pro Gly NH2 Leuprolide D-Leu NEt Goserelin D-Ser NH2 LHRH agonists Triptorelin D-Trp NH2 Buserelin D-Ser NEt Degarelix D-NaI D-Cpa D-PaI Aph D-Aph D-Ala NH2 N-Me ABarelix D-NaI D-Cpa D-PaI D-Asn Lys D-Ala NH2 Tyr GnRH antagonists Cetrorelix D-NaI D-Cpa D-PaI D-Cit D-Ala NH2 Ganirelix D-NaI D-CPa D-PaI D-hArg D-hArg D-Ala NH2 Millar RP, et al. Endocr Rev 2004;25:235–75 Most acute CVD events are caused By rupture of a vulnerable atherosclero@c plaque The vulnerable plaque – thin cap with inflammaon Inflammation Plaque instability is at the heart of cardiovascular disease Stable plaque Vulnerable plaque Lumen Lumen Lipid core Lipid core FiBrous cap FiBrous cap Thick Cap Thin Rich in SMC and matrix Composion Rich in inflammatory cells: proteoly@c ac@vity Poor Lipid Rich Inflammatory Inflammatory state Highly inflammatory LiBBy P. Circulaon 1995;91:2844-2850 Incidence of Both prostate cancer and CV events is highest in older men Prostate cancer CV events 3500 3500 Prostate cancer All CV disease Major CV events 3000 3000 2827.1 2500 2500 2338.9 2000 2000 1719.7 1500 1500 1152.6 1008.7 1038.7 1000 1000 641.2 545.2 571.1 Age-specific incidence per 100,000 person-years 500 500 246.9 133.7 4.3 0 0 40-49 50-59 60-69 70-79 80-89 90-99 40-49 50-59 60-69 70-79 80-89 90-99 CV, cardiovascular Major CV events = myocardial infarc@on, stroke, or death due to CV disease All CV disease = major CV events + self-reported angina or revascularisaon procedures Driver, et al.
    [Show full text]
  • Mouse Model of Male Germ Cell Apoptosis in Response to a Lack of Hormonal Stimulation
    Indian Journal of Experimental Biology Vol. 43, November 2005, pp. 1048-1057 Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation Ami ya P Sinha Hikim*, Yanira Vera, Rashid I Elhag, Yanhe Lue, Yu-Gui Cui , Vanisha Pope, Andrew Leun g, Vince Atienza, Christina Wan g & Ron ald S Swerdloff Di vision of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA and Los Angeles Biomedical Research Institute, Torrance. Californi a. USA Received 5 August 2005 As a prerequisite for studies using mutant mi ce, we established a mouse model for induction of male germ ce ll apoptosis after depri vation of gonadotropins and intratesti c ul ar testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagoni st (GnRH-A), acyline, al one or in combinati on with an anti and rogen, flutamide for effective inducti on of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resul ted in almost th e same level of suppression of spermatogenesis, as judged by testi s weight and by germ cell apoptotic index, in 2 weeks as th at re ported for rats after treatment with 1.25 mg/kg BW Nai-Giu GnRH-A for the same time peri od. Within the study paradi gm, the maximum suppression of spermatogenesis occurred after a single sc injecti on of hi gh (20 mg/kg BW) dose of acyli ne with flutamide.
    [Show full text]
  • The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men
    ORIGINAL ARTICLE Endocrine Research The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men M. Y. Roth, S. T. Page, K. Lin, B. D. Anawalt, A. M. Matsumoto, B. Marck, W. J. Bremner, and J. K. Amory Downloaded from https://academic.oup.com/jcem/article/96/4/1175/2720870 by guest on 02 October 2021 Departments of Internal Medicine (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.) and Obstetrics and Gynecology (K.L.) and Center for Research in Reproduction and Contraception (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.), University of Washington, Seattle, Washington 91895; and Geriatric Research (B.M.), Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98105 Introduction: Concentrations of intratesticular (IT) testosterone (T) are known to be 100–200 times those of serum T; however, the IT concentrations of T’s precursors, their testicular to serum gra- dients, gonadotropin dependence, and response to stimulation with human chorionic gonado- tropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the adminis- tration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. Methods: We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d.
    [Show full text]
  • Gonadotropins Regulate Rat Testicular Tight Junctions in Vivo
    REPRODUCTION-DEVELOPMENT Gonadotropins Regulate Rat Testicular Tight Junctions in Vivo Mark J. McCabe, Gerard A. Tarulli, Sarah J. Meachem, David M. Robertson, Peter M. Smooker, and Peter G. Stanton Prince Henry’s Institute (M.J.M., G.A.T., S.J.M., D.M.R., P.G.S.), Monash Medical Centre, Clayton, Victoria 3168, Australia; School of Applied Sciences (M.J.M., P.M.S.), Royal Melbourne Institute of Technology University, Bundoora, Victoria 3083, Australia; and Department of Biochemistry and Molecular Biology (P.G.S.), Monash University, Clayton, Victoria 3800, Australia Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n ϭ 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonado- tropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immuno- staining.
    [Show full text]
  • Suppression of Kisspeptin Expression and Gonadotropic Axis Sensitivity Following Exposure to Inhibitory Day Lengths in Female Siberian Hamsters
    Hormones and Behavior 52 (2007) 492–498 www.elsevier.com/locate/yhbeh Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters Alex O. Mason a, Timothy J. Greives b, Melissa-Ann L. Scotti b, Jacob Levine a, Stefanie Frommeyer b, Ellen D. Ketterson b, ⁎ Gregory E. Demas b, Lance J. Kriegsfeld a, a Department of Psychology and Helen Wills Neuroscience Institute, 3210 Tolman Hall, MC 1650, University of California, Berkeley, Berkeley, CA 94720-1650, USA b Department of Biology, Center for the Integrative Study of Animal Behavior and Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA Received 10 May 2007; revised 7 July 2007; accepted 10 July 2007 Available online 21 July 2007 Abstract To avoid breeding during unsuitable environmental or physiological circumstances, the reproductive axis adjusts its output in response to fluctuating internal and external conditions. The ability of the reproductive system to alter its activity appropriately in response to these cues has been well established. However, the means by which reproductively relevant cues are interpreted, integrated and relayed to the reproductive axis remain less well specified. The neuropeptide kisspeptin has been shown to be a potent positive stimulator of the hypothalamo–pituitary–gonadal (HPG) axis, suggesting a possible neural locus for the interpretation/integration of these cues. Because a failure to inhibit reproduction during winter would be maladaptive for short-lived female rodents, female Siberian hamsters (Phodopus sungorus) housed in long and short days were examined. In long “summer” photoperiods, kisspeptin is highly expressed in the anteroventral periventricular nucleus (AVPV), with low expression in the arcuate nucleus (Arc).
    [Show full text]
  • Acyline: the First Study in Humans of a Potent, New Gonadotropin-Releasing Hormone Antagonist
    0013-7227/02/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 87(7):3215–3220 Printed in U.S.A. Copyright © 2002 by The Endocrine Society Acyline: The First Study in Humans of a Potent, New Gonadotropin-Releasing Hormone Antagonist KAREN L. HERBST, BRADLEY D. ANAWALT, JOHN K. AMORY, AND WILLIAM J. BREMNER Department of Medicine, University of Washington (K.L.H., B.D.A., J.K.A., W.J.B.) and Medical Service, Department of Veteran Affairs, Puget Sound Health Care System (B.D.A.), Seattle, Washington 98195 Acyline is a novel GnRH antagonist found in animal studies to maintaining suppression for over 48 h. Serum acyline levels -be a potent suppressor of circulating gonadotropin and tes- peaked at1hat18.9 ؎ 0.9 ng/ml, remained significantly ele tosterone (T) levels. We conducted the first study of acyline vated above background 7 d after injection, and returned to administration to humans. Eight healthy, eugonadal young background levels by 14–17 d after injection. Side-effects at men were administered a series of acyline injections (0, 2.5, the site of injection were limited to infrequent blush and pru- 7.5, 25, and 75 ␮g/kg), each injection separated by at least 10 d. ritus that resolved within 90 min of injection. Higher doses of Serum FSH, LH, and T levels were measured for 7 d after acyline might be effective as depot injections for long-lasting injections. Acyline suppressed FSH, LH, and T levels in a dose- gonadotropin suppression in hormone-dependent diseases dependent fashion. Maximal suppression occurred after in- and for use in male hormonal contraception regimens.
    [Show full text]
  • A Focus on the Kisspeptin Receptor, Kiss1r
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 12-1-2014 12:00 AM Pathway-Specific Signaling and its Impact on erF tility: A Focus on the Kisspeptin Receptor, Kiss1r Maryse R. Ahow The University of Western Ontario Supervisor Dr. Andy Babwah The University of Western Ontario Graduate Program in Physiology A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Maryse R. Ahow 2014 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Molecular and Cellular Neuroscience Commons Recommended Citation Ahow, Maryse R., "Pathway-Specific Signaling and its Impact on erF tility: A Focus on the Kisspeptin Receptor, Kiss1r" (2014). Electronic Thesis and Dissertation Repository. 2537. https://ir.lib.uwo.ca/etd/2537 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. PATHWAY-SPECIFIC SIGNALING AND ITS IMPACT ON FERTILITY: A FOCUS ON THE KISSPEPTIN RECEPTOR, Kiss1r (Thesis format: Monograph) by Maryse R. Ahow Graduate Program in Physiology A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Maryse R. Ahow, 2014 Abstract Hypothalamic gonadotropin-releasing hormone (GnRH) is the master regulator of the neuroendocrine reproductive (HPG) axis and its secretion is regulated by various afferent inputs to the GnRH neuron.
    [Show full text]
  • WO 2009/137104 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 12 November 2009 (12.11.2009) WO 2009/137104 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/137 (2006.01) A61K 31/5685 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/138 (2006.01) A61P 35/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/4196 (2006.01) CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) International Application Number: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, PCT/US2009/002885 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, 7 May 2009 (07.05.2009) NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, (25) Filing Language: English UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/127,025 9 May 2008 (09.05.2008) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, (71) Applicant (for all designated States except US): RA¬ TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, DIUS HEALTH, INC.
    [Show full text]
  • Therapeutic Implications for Castration-Resistant Prostate Cancer
    Research Article Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for Castration-Resistant Prostate Cancer Elahe A. Mostaghel,1,2 Stephanie T. Page,2,5 Daniel W. Lin,3,5 Ladan Fazli,6 Ilsa M. Coleman,1 Lawrence D. True,4 Beatrice Knudsen,1 David L. Hess,7 Colleen C. Nelson,6 Alvin M. Matsumoto,2,5 William J. Bremner,2 Martin E. Gleave,6 and Peter S. Nelson1 1Fred Hutchinson Cancer Research Center; Departments of 2Medicine, 3Urology, and 4Pathology, University of Washington School of Medicine; 5Veterans Affairs Puget Sound Health Care System, Seattle, Washington; 6Vancouver General Hospital, Vancouver, British Columbia, Canada; and 7Oregon National Primate Research Center, Beaverton, Oregon Abstract efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contribu- Androgen deprivation therapy (ADT) remains the primary tions to the prostatic androgen microenvironment. treatment for advanced prostate cancer. The efficacy of ADT [Cancer has not been rigorously evaluated by demonstrating suppres- Res 2007;67(10):5033–41] sion of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of Introduction medical castration in suppressing prostatic androgen levels Androgens are important mediators of transcriptional pathways and androgen-regulated gene expression. Androgen levels and controlling the proliferation, differentiation, and apoptosis of androgen-regulated
    [Show full text]
  • April 16,2004 Steve E. Phurrough, MD, MPA Office of Clinical Standards & Quality Centers for Medicare and Medicaid Services
    April 16,2004 Steve E. Phurrough, MD, MPA Office of Clinical Standards & Quality Centers for Medicare and Medicaid Services 7500 Security Boulevard Mail Stop C1-09-06 Baltimore, MD 21244-1850 Dear Dr. Phurrough: This is a formal request for a national coverage determination ("NCD") on the use of Plenaxis™ (abarelix for injectable suspension) under the Medicare program. This request is being made pursuant to NCD development Track #1 - Requests for New National Coverage Determinations Initiated by Any Party, Including Beneficiaries, Manufacturers, Providers, or Suppliers. We believe that Plenaxis meets the qualifications for coverage in the Medicare benefit category of "drugs or biologicals," as defined under § 1861(t)(1) of the Social Security Act. Plenaxis (abarelix for injectable suspension) is a synthetic decapeptide with potent antagonistic activity against naturally occurring gonadotropin releasing-hormones (GnRH). It is the only GnRH antagonist ever to have been approved by the Food and Drug Administration ("FDA") as a treatment for prostate cancer. Specifically, Plenaxis was first approved by FDA on November 25, 2003 for the palliative treatment of men with advanced symptomatic prostate cancer, in whom LHRH agonist therapy is not appropriate and who refuse surgical castration, and have one or more of the following: (1) risk of neurological compromise due to metastases, (2) ureteral or bladder outlet obstruction due to local encroachment or metastatic disease, or (3) severe bone pain from skeletal metastases persisting on narcotic analgesia. On March 31, 2004, Plenaxis was approved for inclusion in the United States Pharmacopeia Drug Information.® Enclosed you will find three copies of a two compact disc ("CD") set containing the supporting documentation for this NCD request.
    [Show full text]