Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models

Endocrinology
H Z KeD D Thompson

Abstract

We have discovered a new, nonsteroidal, potent estrogen agonist/antagonist, CP-336,156. CP-336,156 binds selectively and with high affinity to the human estrogen receptor-alpha with a half-inhibition concentration of 1.5 nM, which is similar to that seen with estradiol (4.8 nM). When given orally to immature (3-week-old) female Sprague-Dawley rats for 3 days at doses of 0.1, 1.0, 10, or 100 microg/kg x day, unlike 17alpha-ethynyl estradiol, CP-336,156 had no effect on uterine wet or dry weight. Similarly, no uterine hypertrophy was observed in aged (17-month-old) female rats treated (p.o.) with CP-336,156 at 10 or 100 microg/kg x day for 28 days. We also found that CP-336,156 decreased total serum cholesterol and fat body mass and had no effect on lean body mass in these aged female rats. In 5-month-old ovariectomized (OVX) Sprague-Dawley female rats, CP-336,156 completely prevented OVX-induced increases in body weight gain, total serum cholesterol, and serum osteocalcin at doses between 10 and 1000 microg/kg x day after 4 weeks. At these doses, CP-336,156 completely prevented OVX-induced bone loss and inhibited the increased bone turnover associated with estrogen deficiency in lumbar vertebrae, proximal tibiae, and distal femo...Continue Reading

References

Sep 1, 1992·Bone and Mineral·H M Frost, W S Jee
Dec 1, 1991·Bone and Mineral·D N Kalu
Jan 1, 1991·American Journal of Clinical Oncology·U EppenbergerW Küng
Dec 1, 1987·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A M ParfittR R Recker
May 1, 1987·American Journal of Obstetrics and Gynecology·M I Whitehead, D Fraser
Oct 1, 1987·Breast Cancer Research and Treatment·V C JordanJ U Lindgren
Jan 1, 1969·Calcified Tissue Research·H M Frost
Apr 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·P A Price, S K Nishimoto
Sep 1, 1995·American Journal of Obstetrics and Gynecology·R A Lobo
Jan 1, 1995·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·P MaximG M Spitalny
Jun 15, 1995·The New England Journal of Medicine·G A ColditzF E Speizer
Nov 1, 1994·Endocrinology·C H TurnerH U Bryant
Oct 1, 1995·Bone·G L Evans, R T Turner
Aug 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·H K ChenD D Thompson
May 1, 1997·Journal of Cellular Biochemistry·W A GrasserV M Paralkar

❮ Previous
Next ❯

Citations

May 27, 2009·Genes & Nutrition·M PenzaDiego Di Lorenzo
May 31, 2012·Chemical Research in Toxicology·Bradley T MichalsenJudy L Bolton
May 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Susie Y DaiPatrick R Griffin
Jun 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Rebecca L RichDavid G Myszka
Aug 10, 2010·Core Evidence·Luigi GennariRanuccio Nuti
Nov 10, 2009·Therapeutics and Clinical Risk Management·E Michael Lewiecki
Mar 18, 2009·Pharmacogenomics·Luigi GennariRanuccio Nuti
Feb 16, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A S Levenson, V C Jordan
Apr 24, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·H Z KeD D Thompson
Aug 26, 2000·Current Opinion in Chemical Biology·F J López
Feb 13, 2001·The Journal of Steroid Biochemistry and Molecular Biology·V C Jordan
Aug 19, 2006·Expert Opinion on Investigational Drugs·Luigi GennariRanuccio Nuti
Apr 1, 2003·Expert Opinion on Investigational Drugs·Diane M Biskobing
Feb 1, 2011·Expert Opinion on Drug Discovery·Luigi GennariRanuccio Nuti
Mar 26, 2002·Climacteric : the Journal of the International Menopause Society·S L SilfenH U Bryant
Apr 24, 2009·Climacteric : the Journal of the International Menopause Society·A Nath, R Sitruk-Ware
Oct 28, 2015·Climacteric : the Journal of the International Menopause Society·M R McClung
May 13, 2014·BioMed Research International·Sreeja SreekumarSreeja Sreeharshan
May 27, 2008·American Journal of Obstetrics and Gynecology·J Mark ClineRobert Brommage
Apr 17, 2001·American Journal of Obstetrics and Gynecology·R A Wild, S E Reis
May 7, 2005·Advanced Drug Delivery Reviews·Cedo M Bagi
Sep 5, 2006·Clinical calcium·Toshio Matsumoto
Jun 19, 2004·Bioorganic & Medicinal Chemistry Letters·Qiang TanMilton L Hammond
Jun 19, 2004·Bioorganic & Medicinal Chemistry Letters·Qiang TanMilton L Hammond
Apr 25, 2007·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M G SørensenM A Karsdal
Apr 26, 2007·Protein Science : a Publication of the Protein Society·Felix F VajdosJayvardhan Pandit
Mar 29, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Barry S Komm, Sebastian Mirkin
Feb 13, 2014·Menopause : the Journal of the North American Menopause Society·Sebastian MirkinBarry S Komm
Jul 30, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Gregg D CapponMark E Hurtt
Jul 30, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·K K TerryU Gupta
Jul 30, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·T R S Ozolins, U Gupta
Jul 30, 2004·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Walter P WeisenburgerMelissa S Tassinari
Dec 10, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yanfei L MaMasahiko Sato
Nov 19, 2005·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Reina Armamento-VillarealRoberto Civitelli
Jun 1, 2006·Menopause : the Journal of the North American Menopause Society·Michael R McClungAndrew Lee
Jun 1, 2006·Menopause : the Journal of the North American Menopause Society·Steven R Goldstein
Apr 1, 2002·Journal of the American Aging Association·H Z KeD D Thompson
Jul 14, 2006·Menopause : the Journal of the North American Menopause Society·Xiao-Ning WangDavid D Thompson
Nov 1, 2006·Menopause : the Journal of the North American Menopause Society·Cynthia LeesRobert Brommage
Dec 13, 2006·Cancer Metastasis Reviews·Muzaffer Cicek, Merry Jo Oursler
Aug 7, 2010·Menopause : the Journal of the North American Menopause Society·Steven R GoldsteinUsha Sriram

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis