DOCSLIB.ORG

Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts'

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts' BIOLOGY OF REPRODUCTION 56, 272-278 (1997) Estrogen Stimulation of P450 Cholesterol Side-Chain Cleavage Activity in Cultures of Human Placental Syncytiotrophoblasts' Jeffery S. Babischkin,3 Randall W. Grimes,3 Gerald J. Pepe, 4 and Eugene D. Albrecht2,3 Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology,' Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201 Department of Physiology Eastern Virginia Medical School, Norfolk, Virginia 23501 ABSTRACT biochemical differentiation of the latter cells that is mani- fested as an increase in expression of the LDL receptor and Downloaded from https://academic.oup.com/biolreprod/article/56/1/272/2760805 by guest on 29 September 2021 The present study determined whether estrogen has a role in regulating the P450 cholesterol side-chain cleavage enzyme P450,,, enzyme system. (P450_cc) and/or de novo/deesterification cholesterol pathways Recently, we reported that LDL uptake was increased in involved in progesterone biosynthesis within human syncytiotro- human syncytiotrophoblast cells cultured with estrogen [7] phoblasts. Human placental syncytiotrophoblasts were cultured and suggested that estrogen also regulates key steps in the for 48 h with estradiol, and P450,,,cc activity was determined by placental progesterone pathway in human pregnancy. How- the formation of progesterone from 25-hydroxycholesterol. Es- ever, it remains to be determined whether estrogen also reg- tradiol at 10 7 or 10 6 M and 25-hydroxycholesterol increased ulates the P450,s,-catalyzed utilization of cholesterol sub- mean ( SE) progesterone production by syncytiotrophoblasts strate in human syncytiotrophoblasts. Moreover, although (ng/0.5 x 106 cells) to a value (19.2 - 1.1) that was 104% (p the de novo and deesterification pathways appear to have < 0.001) higher than that of the untreated controls (9.4 + 0.8) a minor role in providing cholesterol substrate for steroid- and 52% higher (p < 0.001) than with 25-hydroxycholesterol ogenesis within the human trophoblast [8, 9], it is not alone (12.6 0.9). The stimulation of progesterone secretion known whether these cholesterol synthetic pathways are apparently was not the result of a change in progesterone me- regulated by estrogen. tabolism to its principal metabolite, because 20a-hydroxypregn- In the present study, therefore, we determined the effect 4-en-3-one represented a minor secretory component (0.7-1.7 of estrogen on P450,.c activity and mRNA levels, on the ng/0.5 x 106 cells) under these conditions, and levels were not de novo pathway involving the rate-limiting 3-hydroxy-3- substantially altered by estrogen. In contrast to the stimulatory methylglutaryl coenzyme-A (HMG-CoA) reductase en- effect of estradiol on P450scc activity, estrogen did not alter ei- zyme, and on the deesterification/esterification pathway in- ther the P450c c mRNA levels or the activities of 3-hydroxy-3- volving the rate-limiting cholesterol ester hydrolase/acyl methylglutaryl coenzyme-A reductase and cholesterol ester hy- coenzyme A-cholesterol acyltransferase (ACAT) in cultures drolase-rate-limiting enzymes for the de novo and deesterifi- of human syncytiotrophoblasts. cation pathways, respectively, for cholesterol formation in syn- cytiotrophoblasts in culture. Collectively, these results indicate that estrogen regulates the P450,cc component of the progester- MATERIALS AND METHODS one biosynthetic pathway, which we suggest signals functional/ Placental Collection and Trophoblast Preparation biochemical differentiation of syncytiotrophoblasts during pri- mate pregnancy. Human placentas were obtained immediately after un- complicated elective cesarean section at term, and cytotro- INTRODUCTION phoblasts were isolated essentially as described by Kliman et al. [10]. Briefly, placental villous tissue was dispersed at We have recently shown that there was an estrogen-de- 37°C in calcium-magnesium-free Hanks' Balanced Salt So- pendent developmental increase in low-density lipoprotein lution (GIBCO, Grand Island, NY), containing 4.0 mM so- (LDL) receptor and P450 cholesterol side-chain cleavage dium bicarbonate, 10.0 mM HEPES, 50 lpg/ml gentamicin (P450,,c) mRNA levels [1, 2] and LDL uptake [3, 4] in pla- sulfate, 50 IU/ml penicillin G, 50 pLg/ml streptomycin sul- cental syncytiotrophoblasts during advancing stages of ba- fate, 0.125% trypsin (bovine pancreas type III; Sigma boon pregnancy when estrogen levels become elevated. Chemical Co., St. Louis, MO), and 1500 kunitz U/mg DNa- Therefore, we have proposed that estrogen has a central se I (bovine pancreas type IV; Sigma). The cell suspensions integrative role in regulating those components of the pro- obtained from digestion were then layered onto a 5-70% gesterone biosynthetic pathway critical to the cellular up- (v:v) Percoll (Pharmacia LKB Biotechnology, Piscataway, take of substrate cholesterol and its metabolism to proges- NJ) gradient, and a cytotrophoblast-enriched cell fraction terone thereafter within the placenta ([5, 6] for reviews). was isolated by centrifugation at 1200 x g for 20 min at Moreover, because the ontogenetic increase in receptor-me- room temperature. diated LDL uptake and the P450scc enzyme occurred within syncytiotrophoblasts, we have proposed that after morpho- logical differentiation of cytotrophoblasts into syncytiotro- Culture phoblasts, there is a further estrogen-regulated functional/ Purified cytotrophoblasts (0.5-2.0 x 106 cells/ml) were incubated in 1 ml Dulbecco's Modified Eagles Medium Accepted September 11, 1996. (DMEM) containing 10% (v:v) fetal bovine serum, 44 mM Received July 8, 1996. sodium bicarbonate, 25 mM HEPES, 50 Rpg/ml gentamicin 'This work was supported by NIH Research Grant R01 HD-13294. 'Correspondence: Eugene D. Albrecht, Department of Obstetrics, Gv- sulfate, 50 IU/ml penicillin G, and 50 ,ag/ml streptomycin necology, and Reproductive Sciences, University of Maryland School of sulfate in 24-well culture plates (CoStar, Cambridge, MA) Medicine, Bressler Research Laboratories 11-017, 655 West Baltimore for 72 h at 37°C in a humidified atmosphere of 10% CO2: Street, Baltimore, MD 21201. FAX: (410) 706 5747. 90% air to allow for cell attachment, aggregation, and for- 272 P450,CC IN HUMAN PLACENTAL SYNCYTIOTROPHOBLASTS 273 mation of syncytia. Syncytiotrophoblast cultures were (Eastman Kodak, Rochester, NY). The level of mRNA ex- washed, incubated in serum-free DMEM for 48 h, and then pression was analyzed by autoradiographic densitometry incubated for 48 h in the presence of serum-free DMEM using a model 620 Video Densitometer (Bio-Rad, Rich- and various concentrations of estradiol-173 or other ster- mond, CA). oids (Sigma), 100 pxg/ml aminoglutethimide (Sigma), or 62 RIM 25-hydroxycholesterol (Steraloids, Wilton, NH) to as- HMG-CoA Reductase Activity sess P450,cc activity. Because 25-hydroxycholesterol readi- HMG-CoA reductase activity was measured by the for- ly traverses the plasma and mitochondrial membranes to 4 4 gain access to the terminal oxidase of the P450,cc, its con- mation of ['1 C]mevalonolactone from [1 C]HMG-CoA es- version into progesterone provides an index of P450,cc ac- sentially as described by Kubo and Strott [16]. Trophoblast tivity [11, 12]. In those cultures in which P450.cc mRNA cells were sonicated and then incubated (60 min; 37°C) in expression, HMG-CoA reductase, cholesterol ester hydro- 100 mM potassium phosphate buffer, pH 7.4, containing 20 lase, and ACAT were determined, the first 48-h serum-free mM glucose-6-phosphate (Sigma), 2.5 mM NADP (Sigma), 3.5 U/ml glucose-6-phosphate dehydrogenase (Sigma), 50 DMEM interval was omitted. At the end of all treatment Downloaded from https://academic.oup.com/biolreprod/article/56/1/272/2760805 by guest on 29 September 2021 periods, culture media were stored at -20°C until assayed mM NaCl, 5 mM dithiothreitol (Boehringer Mannheim), 10 mM EDTA, 0.1% (v:v) Triton X-100 (Sigma), and 2.5-200 for progesterone and 20a-hydroxypregn-4-en-3-one. Cells 4 were washed with 0.9% NaCl, and either RNA was isolated ,uM [' C]HMG-CoA (New England Nuclear-Dupont Co., for Northern blot analysis of P450,cc or cells were assessed Wilmington, DE). Reactions were terminated by addition of 0.05 ml of 5 N HCI, and after addition of 40 000 d.p.m. for activity of cholesterol metabolism enzymes as described 3 below. A small fraction of cells was also solubilized in 0.1 [ H]mevalonic acid (New England Nuclear-Dupont) as re- covery indicator, media were applied to 1-ml Bio-Rex 5 N NaOH for protein determination [13] or suspended in 1 14 3 ml 0.01 M Tris buffer and stored at -20°C until assayed (Bio-Rad) columns, and [ C/ H]mevalonolactone was elut- fluorometrically for cellular DNA content [14]. ed with 2 ml water. More than 95% of mevalonolactone was eluted from the column while 99% of [14C]HMG-CoA RIA was retained. HMG-CoA reductase specific activity was de- termined by the amount of ['4 C]mevalonolactone formed The contents of progesterone and 20a-hydroxypregn-4- in the presence of cells minus that measured in the absence en-3-one in the media were determined by RIA after puri- of cells. fication of samples on Sephadex LH-20 columns (Isolab, Inc., Akron, OH), as described previously [15], using high- Cholesterol Ester Hydrolase Activity ly specific antisera to progesterone (generously provided by Gordon Niswender, Colorado State University, Boulder, Neutral pH cholesterol ester hydrolase activity was mea- CO) and 20a-hydroxypregn-4-en-3-one (Endocrine Sci- sured in trophoblast cells by the formation of ['4 C]oleic ences, Tarzana, CA). acid from ['4 C-oleoyl]cholesteryl oleate by methods adapt- ed from Wittmaack et al. [17] and Miller and Small [18]. Northern Analysis of P450,,. Cells were incubated in 0.05 M Tris-HCI buffer (pH 7.4 at 37°C) containing 4.2 mg/ml fatty acid-free BSA (Sigma) RNA was prepared and analyzed by Northern blot hy- and 2.5-150 M [14 C-oleoyl]cholesteryl oleate (Amer- bridization as described previously [1].
Load more

Recommended publications
  • Tamoxifen As the First Targeted Long-Term Adjuvant Therapy for Breast
    V C Jordan Adjuvant tamoxifen therapy for 21:3 R235–R246 Review breast cancer Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer Correspondence V Craig Jordan should be addressed to V C Jordan Departments of Oncology and Pharmacology, Lombardi Comprehensive Cancer Center, Georgetown University Email Medical Center, Washington, District of Columbia 20057, USA [email protected] Abstract Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine Key Words has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other " breast medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ,and " endocrine therapy male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that ‘longer was going to be better’ when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these Endocrine-Related Cancer factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. Endocrine-Related Cancer (2014) 21, R235–R246 Introduction ‘Science is adventure, discovery, new horizons, insight into our and invariably unsuccessful (except for childhood world, a means of predicting the future and enormous power leukemia).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,623.422 B2 Hansen Et Al
    USOO8623422B2 (12) United States Patent (10) Patent No.: US 8,623.422 B2 Hansen et al. (45) Date of Patent: *Jan. 7, 2014 (54) COMBINATION TREATMENT WITH 5,668,161 A 9/1997 Talley et al. STRONTUM FOR THE PROPHYLAXIS 5,681,842 A 10, 1997 Dellaria et al. AND/OR TREATMENT OF CARTILAGE 5,686.460 A 11/1997 Nicolai et al. AND/OR BONE CONDITIONS 5,686,470 A 11/1997 Weier et al. 5,696,431 A 12/1997 Giannopoulos et al. 5,707,980 A 1/1998 Knutson (75) Inventors: Christian Hansen, Vedback (DK); 5,719,163 A 2f1998 Norman et al. Henrik Nilsson, Copenhagen (DK); 5,750,558 A 5/1998 Brooks et al. Stephan Christgau, Gentofte (DK) 5,753,688 A 5/1998 Talley et al. 5,756,530 A 5/1998 Lee et al. (73) Assignee: Osteologix A/S, Copenhagen (DK) 5,756,531 A 5/1998 Brooks et al. 5,760,068 A 6/1998 Talley et al. (*) Notice: Subject to any disclaimer, the term of this 5,776,967 A 7/1998 Kreft et al. patent is extended or adjusted under 35 5,776,984. A 7/1998 Dellaria et al. U.S.C. 154(b) by 558 days. 5,783,597 A 7/1998 Beers et al. This patent is Subject to a terminal dis 5,807,873 A 9, 1998 Nicolai et al. claimer. 5,824,699 A 10, 1998 Kreft et al. 5,830,911 A 11/1998 Failli et al. 5,840,924 A 11/1998 Desmond et al.
    [Show full text]
  • Tamoxifen As the First Targeted Long-Term Adjuvant Therapy For
    V C Jordan Adjuvant tamoxifen therapy for 21:3 R235–R246 Review breast cancer Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer Correspondence V Craig Jordan should be addressed to V C Jordan Departments of Oncology and Pharmacology, Lombardi Comprehensive Cancer Center, Georgetown University Email Medical Center, Washington, District of Columbia 20057, USA [email protected] Abstract Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine Key Words has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other " breast medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinoma in situ,and " endocrine therapy male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that ‘longer was going to be better’ when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation with Nature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these Endocrine-Related Cancer factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society. Endocrine-Related Cancer (2014) 21, R235–R246 Introduction ‘Science is adventure, discovery, new horizons, insight into our and invariably unsuccessful (except for childhood world, a means of predicting the future and enormous power leukemia).
    [Show full text]
  • S Health and Menopause
    National Heart, Lung, and Blood Institute Office of Research on Women’s Health Giovanni Lorenzini Medical Science Foundation I NTERNATIONAL P OSITION P APER on W OMEN’ S H EALTH AND M ENOPAUSE: ACOMPREHENSIVE A PPROACH NATIONAL INSTITUTES OF HEALTH I NTERNATIONAL P OSITION P APER on W OMEN’ S H EALTH AND M ENOPAUSE: ACOMPREHENSIVE A PPROACH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE OFFICE OF RESEARCH ON WOMEN’S HEALTH NATIONAL INSTITUTES OF HEALTH AND GIOVANNI LORENZINI MEDICAL SCIENCE FOUNDATION NIH PUBLICATION NO. 02-3284 JULY 2002 CHAIRS AND EDITORS Chair and Editor Cochair and Coeditor Nanette K. Wenger, M.D. Claude J. M. Lenfant, M.D. Professor of Medicine (Cardiology) Director Emory University School of Medicine National Heart, Lung, and Blood Institute Atlanta, GA, U.S.A. National Institutes of Health Bethesda, MD, U.S.A. Cochair and Coeditor Rodolfo Paoletti, M.D. Cochair and Coeditor Professor of Pharmacology Vivian W. Pinn, M.D. Director, Department of Pharmacological Sciences Associate Director for Research on University of Milan Women’s Health Milan, Italy Director, Office of Research on Women’s Health National Institutes of Health Bethesda, MD, U.S.A. PANEL MEMBERS Elizabeth Barrett-Connor, M.D. Louise A. Brinton, Ph.D. Professor and Chief Chief, Environmental Epidemiology Branch Division of Epidemiology National Cancer Institute Department of Family and Preventive Medicine National Institutes of Health University of California, San Diego School of Bethesda, MD, U.S.A. Medicine La Jolla, CA, U.S.A. Aila Collins, Ph.D. Associate Professor Martin H. Birkhäuser, M.D. Psychology Section Professor Department of Clinical Neuroscience Division of Gynecological Endocrinology Karolinska Institute Department of Obstetrics and Gynecology Stockholm, Sweden University of Bern Bern, Switzerland II Peter Collins, M.D.
    [Show full text]
  • OSTEOPOROSIS N. Sema Akalm ABSTRACT INTRODUCTION
    Review Article OSTEOPOROSIS Invited Paper N. Sema Akalm M.D. Sub-department o f Endocrinology, Department of Internal Medicine, School o f Medicine, Marmara University, Istanbul Turkey. ABSTRACT EPIDEMIOLOGY It is estimated that over 1.3 million osteoporotic Osteoporosis represents the most common form of fractures occur each year in the United States. metabolic bone disease. Its epidemiology, Approximately one-half of these fractures are vertebral pathogenesis, clinical manifestations, radiographic fractures, one-quarter are hip fractures, and one- and laboratory features, bone density measurements, quarter are Colles’ fractures (2). Pelvic and hip and treatment are discussed. fractures are associated with increased mortality, although conditions other than the fracture itself may account for most of the deaths (4).The risk of all Key Words : Postmenopausal osteoporosis, fractures rises dramatically with age but osteoporotic Bone mineral density, HRT, Bisphosphonates fractures are not limited to the elderly. The number of women at risk for fracture because of INTRODUCTION radiographic osteoporosis (defined as bone mineral density more than 2 SD below the mean of young Osteoporosis is the most commonly encountered bone women) is much higher than the number of women disease. It is a major risk factor for fracture and leads who actually have fractures.Approximately 30 percent to considerable morbidity, mortality and expense. This of women over the age of 50 have low bone mass, and skeletal disorder is characterized by two elements that the numbers increase with age.Low lumbar spine bone distinguish it from other causes of osteopenia such as mineral density is present in 15 percent of women in osteomalacia and hyperparathyroidism : low bone the sixth decade, and in nearly one-half of all women mass and microarchitectural disruption.
    [Show full text]
  • Role of Environmental Estrogens and Acquired Endocrine Resistance in Breast Cancer and Implications for Treatment with Novel Antiestrogens
    Role of Environmental Estrogens and Acquired Endocrine Resistance in Breast Cancer and Implications for Treatment with Novel Antiestrogens by Thomas Lorenzo Gonzalez A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Toxicology) in the University of Michigan 2018 Doctoral Committee: Assistant Professor Justin A. Colacino, Co-Chair Associate Professor James M. Rae, Co-Chair Professor Rita Loch-Caruso Professor Bhramar Mukherjee Professor Rudy J. Richardson Thomas L. Gonzalez [email protected] ORCID iD: 0000-0003-4497-3106 © Thomas L. Gonzalez 2018 Dedication To my grandparents ii Acknowledgements First, I would like to thank my mentor, Dr. James Rae, for his guidance and unwavering support throughout the duration of my graduate work. From day one, Dr. Rae provided a research environment which allowed me to mature as a scientist, while encouraging me to explore and investigate my own scientific ideas. His commitment to supporting my academic growth has led me to seek out rewarding collaborations with other researchers and develop skills beyond what I expected of myself. I am grateful for his personal investment into my research career and I look forward to continuing our relationship both as colleagues and as friends. Moreover, I am very appreciative of the valuable guidance and time that I have spent working closely with Dr. Justin Colacino who played a critical role in helping me pursue my proposed research ideas during my training. Thank you to each of my committee members Dr. Bhramar Mukherjee, Dr. Rita Loch-Caruso, and Dr. Rudy J. Richardson for the invaluable support and guidance with my dissertation research.
    [Show full text]
  • Dissertation Facklam 2017.Pdf
    Aus der Universitätsfrauenklinik Rostock Direktor Professor Dr. med. habil. B. Gerber DER EINFLUSS DER ORALEN ANTIDIABETIKA METFORMIN UND THIAZOLIDINDION AUF DIE HORMONEXPRESSION HUMANER TROPHOBLASTZELLEN Inauguraldissertation zur Erlangung des akademischen Grades Doktor der Medizin der Medizinischen Fakultät der Universität Rostock vorgelegt von Anna Facklam geboren am 09.01.1986 in Schwerin Rostock, 2016 1 Dekan: Professor Dr. med. univ. E. C. Reisinger Medizinische Fakultät, Universität Rostock 1. Gutachter: Professor Dr. med. V. Briese Universitätsfrauenklinik und Poliklinik, Klinikum Südstadt Rostock 2. Gutachter: Professor Dr. rer. nat. B. Hinz Institut für Pharmakologie und Toxikologie, Universität Rostock 3. Gutachter: Professor Dr. med. E. Schleußner Klinik für Frauenheilkunde und Geburtshilfe, Friedrich-Schiller-Universität Jena Datum der Einreichung: 11. Juni 2016 Datum der Verteidigung: 20. Dezember 2016 2 Inhaltsverzeichnis Abkürzungsverzeichnis .............................................................................................................. 6 Abbildungs- und Tabellenverzeichnis ........................................................................................ 9 1. Einleitung ............................................................................................................................. 10 1.1 Plazenta ........................................................................................................................... 10 1.1.1 Aufbau und Entwicklung der Plazenta....................................................................
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2003/0072760 A1 Sirbasku (43) Pub
    US 2003OO72760A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0072760 A1 Sirbasku (43) Pub. Date: Apr. 17, 2003 (54) ANT-ESTROGEN AND IMMUNE Publication Classification MODULATOR COMBINATIONS FOR TREATING BREAST CANCER 51) Int.nt. Cl.C.7 ....................... A61K 39/395; A61K 31/56 A61K 31/202; A61K 31/137 (76) (52) U.S. Cl. ...................... 424/155.1; 514/170; 514/560; Inventor: David A. Sirbasku, Austin, TX (US) 514/649 Correspondence Address: CONLEY ROSE, PC. (57) ABSTRACT P. O. BOX 3267 Compositions for treating cancers of mucosal tissues includ HOUSTON, TX 77.253-3267 (US) ing breast, prostate, ovary, colon are disclosed which include various combinations of new or conventional anti-estrogen (21) Appl. No.: 10/293,439 compounds, aromatase inhibitors, immune modulators, Filed: Nov. 13, 2002 immune inhibitors, immune inhibitor mimicking com (22) pounds and steroid or thyroid hormones. Methods of pre Related U.S. Application Data dicting Susceptibility of a cancer of mucosal origin to treatment with a composition containing an immune inhibi (63) Continuation-in-part of application No. 09/852,958, tor or an immune inhibitor mimicking compound are also filed on May 10, 2001. Continuation-in-part of appli disclosed. Preferred methods include identifying in a speci cation No. 09/852,547, filed on May 10, 2001. men of cancer cells the presence of a Poly-Ig (Fc) receptor or Poly-Ig-like (Fc) receptor capable of binding to an immune inhibitor or an immune inhibitor mimicking com (60) Provisional application No. 60/332,801, filed on Nov. pound and of mediating immune inhibition of cancer cell 14, 2001.
    [Show full text]
  • International Journal for Pharmaceutical Research Scholars
    International Journal for Pharmaceutical Research Scholars (IJPRS) V-3, I-2, 2014 ISSN No: 2277 - 7873 RESEARCH ARTICLE Anti-Fertility Activity of Pterocarpus Santalinus Heart Wood Extracts in Female Rats Azamthulla M*1, Balasubramanian R2, Kavimani S3 1M S Ramaiah College of Pharmacy, MSRIT Post, MSR Nagar, Bangalore-560 078, PRIST University, Centre for Research and Development, Vallam, Thanjavur, Tamil Nadu- 613403, India. 2Department of Pharmacology, Faculty of Medicine, Sebha University, Sebha, Libya PRIST University, Centre for Research and Development, Vallam, Thanjavur, Tamil Nadu- 613403, India. 3College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health Science, Pondicherry- 6050006, India. Manuscript No: IJPRS/V3/I2/00183, Received On: 14/04/2014, Accepted On: 20/04/2014 ABSTRACT The present study was undertaken to evaluate the anti-fertility activity of Pterocarpus santalinus heart wood using different experimental models such as Anti-implantation activity, Estrous cycle study, and estrogenic /Anti-estrogenic activity. Toxic symptoms and mortality was studied for both ethanol and chloroform extract of Pterocarpus santalinus heart wood and both the extracts were found to be well tolerated up to 2g/kg. Hence 1/4th (500mg/kg) and 1/10th (200mg/kg) of the dose of this were selected for the study. Ethynyl estradiol 0.1g/rat, i.m. (EED) was used as standard drug. The ethanol extract of Pterocarpus santalinus heart wood in both doses (500mg/kg and 200mg/kg) possesses anti-implantation activity by significantly reduced the number of implantation sites. Administration of ethanol extract to immature rats at doses 500 and 200mg/kg showed increase in the ovary weight and also resulted in increase in the levels of alkaline phosphatase and glucose levels but also showed a significant increase in the cholesterol level and hence proved to be an anti-fertility agent.
    [Show full text]
  • Effects of Antiestrogens on Eating, Female Sexual Behavior, and the Uptake of 3H-Estradiol in the Central Nervous System in Rats
    University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations 1896 - February 2014 1-1-1977 Effects of antiestrogens on eating, female sexual behavior, and the uptake of 3H-estradiol in the central nervous system in rats. Edward J. Roy University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_1 Recommended Citation Roy, Edward J., "Effects of antiestrogens on eating, female sexual behavior, and the uptake of 3H-estradiol in the central nervous system in rats." (1977). Doctoral Dissertations 1896 - February 2014. 1701. https://scholarworks.umass.edu/dissertations_1/1701 This Open Access Dissertation is brought to you for free and open access by ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations 1896 - February 2014 by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. EFFECTS OF ANTIESTROGENS ON EATING, FEMALE SEXUAL BEHAVIOR, AND THE UPTAKE OF ^H-ESTRADIOL IN THE CENTRAL NERVOUS SYSTEM IN RATS A Dissertation Presented by EDWARD J. ROY Submitted to the Graduate School of the University of Massachusetts in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY February 1977 Psychology EFFECTS OF ANTIESTROGENS ON EATING, FEMALE SEXUAL 3 BEHAVIOR, AND THE UPTAKE OP H-ESTRADIOL IN THE CENTRAL NERVOUS SYSTEM IN RATS A Dissertation by Edward J, Roy Approved as to style and content by: Dr. George N. Wade, Chairman of Committee Dr. Mark I, Friedman, Member Dr. Maurille J. Fournier, Member Dr. Mkrk S. Fischer, Member Dr. Bonnie R. Stricklsind, Psychology Department Chairperson Acknowledgments The energy and enthusiasm that went into my work on these projects were derived largely from the enjoyment of sharing the successes and frustrations with my friends in the lab.
    [Show full text]
  • A Dissertation Entitled Novel Actions of Steroid Receptors That Limit
    A Dissertation Entitled Novel Actions of Steroid Receptors that Limit Treatment Response in Breast and Lung Cancers by Mugdha Patki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biomedical Science Dr. Manohar Ratnam, Committee Chair Dr. Ivana de la Serna, Committee Member Dr. Stephan M. Patrick, Committee Member Dr. Edwin R. Sanchez, Committee Member Dr. Robert J. Trumbly, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo December 2013 Copyright 2013, Mugdha Patki This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Novel Actions of Steroid Receptors that Limit Treatment Response in Breast and Lung Cancers by Mugdha Patki Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biomedical Science The University of Toledo December 2013 The primary physiological role of estrogens is the development of secondary sexual characteristics including development and function of the normal breast, reproductive system, bone homeostasis, cognitive functions and cardiovascular system. Estrogen has also been implicated as a major player in the progression of normal breast epithelial tissue to a carcinoma. The role of estrogens in breast cancer has been studied extensively and mainly attributed to the transcriptional activation of growth genes through the estrogen receptor. Along with activation of genes, estrogen is also responsible for repression of many genes. Anti-estrogens antagonize both gene activation and gene repression by estrogen. However, the significance and physiological relevance of gene repression by estrogen is poorly understood.
    [Show full text]
  • Permuted Alphabetic List
    PERMUTED ALPHABETIC LIST OF ALL ENGLISH TERMS RESULTING FROM THE MERGING OF THE THREE INITIAL VOCABULARIES: Population multilingual thesaurus (Popin), Popline thesaurus, Multilingual demographic dictionary Bold type: descriptors proposed for acceptance Standard type: equivalents of descriptors Terms followed by ??: terms to be particularly examined Italic type: terms proposed to be moved aside.
    [Show full text]