DOCSLIB.ORG

Action of a Novel Nonsteroidal Antiandrogen, AA560 KEIZO

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Action of a Novel Nonsteroidal Antiandrogen, AA560 KEIZO Endocrinol. Japon. 1980, 27 (1), 69-76 Action of a Novel Nonsteroidal Antiandrogen, AA560 KEIZO SHIDA1, HIDETOSHI YAMANAKA1, ATSUSHI KOYA1, KATSUMIWAKABAYASHI2, HIROSHIMORI3, KENYU SHIBATA3 ANDEIICHIRO SHIMAZAWA3 1D epartment of Urology School of Medicine, Gunma University, Maebashi, 'Hormone Assay Center, Institute of Endocrinology, Gunma University, Maebashi, 3Research Division, Teikoku Hormone Mfg. Co., Kawasaki Synopsis The antiandrogenic properties of a new nonsteroidal antiandrogens, AA560 (N- (2-chloromethyl-2-hydroxypropionyl)-3, 4, 5-trichloroaniline) were investigated. The ventral prostate, dorselateral prostate and coagulating gland weights in rats given AA560 at1-9mg/head were significantly less than those in the intact rats. The seminal vesicle weights in rats given3-9mg/head were significantly less than those of the intact group. In intact animals given daily3or9mg of AA560there were significantly increases of serum FSH, LH and testosterone concentrations. In the in vivo experiment, the pretreatment with AA560decreased the uptake of 3H-androgens in the nuclear fraction of the ventral prostate. On the other hand, a significant increase in the uptake of3H-radioactivity in the cytosol fraction was observed. It was proved by the in vitro displacement study that AA560inhibited the binding of5a-dihydrotestosterone with a receptor protein in the prostatic cytosol. An intensive effort has been directed the transfer of5a-DHT into nucleus (Belham toward the research of antiandrogens because and Neal, 1971; Mangan and Mainwaring, of usefulness of these druge in a variety of 1972). On the other hand, SK&F7690was endocrinological disorders including hirsu- reported to inhibit the cytosol receptor bin- tism, acne, male pattern baldness, benign ding to5a-DHT and the rate of 5a-DHT prostatic hypertrophy and prostatic cancer. formation (Tveter, 1971; Shimazaki et al., A number of antiandrogens have been re- 1972). The representative of nonsteroidal ported, most of which have steroidal stru- antiandrogens is SCH13521 (Flutamide). ctures. The representatives of steroidal an- SCH13521 has been reported to have potent tiandrogens are Cyproterone acetate, Chlor- madinone acetate, Megestrol acetate, SK& Abbreviations used are: F7690and BOMT. Cyproterone acetate and Cyproterone acetate; 6ƒ¿-chloro-17ƒ¿-hydroxy-1ƒ¿, 2a- BOMT compete with 5a-dinydrotestosterone methylene-4, 6-pregnadiene-3, 20-dione-17-acetate. Chlormadinone acetate; 6ƒ¿-chloro-17a-acetoxy-4, 6- (5a-DHT) for the specific, high affinity ben- pregnadiene-3, 20-dione. ding site in the cytosol of prostate and reduce Megestrol acetate; 17ƒ¿-hydroxy-6-methylpregna-4, 6- diene-3, 20-dione-acetate. Received June4, 1979. BOMT; 6ƒ¿-bromo-17/3-hydroxy-17a-methy1-4-oxa-5ƒ¿- * Department of Urology, School of Medicine, androstane-3-one. Gunma University, Maebashi. SK&F7690; 17ƒ¿-methyl-B-nortestosterone. ** Hormone Assay Center, Institute of Endocrino- SCH13521; N-butyryl-3-trifluoromethyl-4-nitroani- logy, Gunma University, Maebashi. line. *** Research Division, Teikoku Hormone Mfg. Co., AA560; N-(2-chloromethyl-2-hydroxypropionyl)-3, 4, Kawasaki. 5-trichloroaniline. Endocrinol. Japon. 70 SHIDA et al. February1980 antiandrogenic effects in the experimental animals (Neri et al., 1972; Neri and Mon- ahan, 1972; Liao et al., 1974; Varkarakis et al., 1975; Surfin and Coffey, 1976) and humans (Irwin and Prout, 1973; Stoliar and Albert, 1974; Prout et al., 1975). This re- -port deals with the antiandrogenic proper- ties of a new nonsteroidal compound, AA Fig.1. Chemical structure of AA560. 560 (N-(2-chloromethyl-2-hydroxypropionyl) -3, 4, 5-trichloroaniline)(Fig.1). concentration (8-12mg/ml). The condensed super- natant fluid was mixed with10ul/ of an ethanol solution of 3H-DHT and100ƒÊl of glycerol to give Materials and Methods final concentrations of2•~10-9m and10 (v/v), re- spectively, and was incubated for3.5hr at0•Ž by Chemicals gentle shaking in the absence or presence of non- radioactive competing compounds dissolved in 5ul (1, 2-3H) testosterone (59Ci/mmole) and (1, 2-3H) 5a-DHT (48Ci/mmol) were obtained from Radio- of ethanol. Then an equal volume of0.25% (w/v) chemical Centre, Amersham, England. Cyproterone dextran-2.5%(w/v) charcoal-10% (v/v) glycerol in -acetate was a gift from Schering AG, Berlin. Chlor- in TEM buffer was added and vortexed for5sec. madinone acetate, AA560and SCHI3521were ob- After centrifugation at8,000•~g for10min, clear tained from Teikoku Hormone Mfg. Co., Kawasaki. supernatant fluids were counted to estimate the pro- tein bound radioactivity. Animals Male Wistar strain rats were maintained on labo- Sucrose density gradient analysis ratory chow of Japan Clea Co. and water ad libitum. After dextran-charcoal treatment, 0.2ml of the supernatant was layered on the top of a sucrose Animals were housed in metabolic cages in a tem- perature-controlled room under a12hr light-12hr gradient (5to20% linear in Hitachi RPS 65T roter tube) containing1.5mm EDTA, 2mm2-mercaptoe- d ark lighting schedule. Orchiectomy was performed thanol, 10% (v/v) glycerol and50mm Tris-HC1, via the scrotal route under ether anaesthesia. The pH7.4. The tube was centrifuged at178,900•~g dose and schedule of the injection are given in detail for21hr at2•Ž. Fractions (0.1ml each) were col- in foot-notes to Table. Sprague-Dawley strain (JCL: lected using a density gradient fractionater (ISCO, SD) rats weighing250-300g were used for the in -vivo and in vitro displacement studies Model640), and the radioactivities were measured. Radioactivity measurement Preparation of subcellular fraction Aqueous samples containing tritium were dissolved The ventral prostates were removed and homo- in a mixture of1.0ml water, 1.0ml ethyl alcohol genized with a Potter-Elvehjem homogenizer in cold and10ml toluene containing0.4% PPO and0.01% v0.05M Tris-HC1 buffer, pH7.4containing0.25M POPOP, and then vortexed for30sec. to extract sucrose and1mM MgC12. The homogenate was cen- the labelled steroid from the aqueous phase. Radio- trifuged at600•~g for10min. and then at105,000•~g activity was counted in a Packard Tri Carb liquid for60min., to yield the prostatic cytosol fraction. scintillation spectrometer, Model 3380, with a count- The crude nuclear fraction (600•~g) was suspended ing efficiency of37-47%. in2.4M sucrose-1mM MgC12, and then centrifuged in a Hitachi RPS27roter at93700•~g for40min., at0•K-2•Ž, to yield the purified nuclear fraction. Protein assay Protein was determined by the method of Lowry et al. (1951). In vitro displacement studies The prostatic tissues were gently homogenized with a Potter-Elvehjem homogenizer in cold50mm Serum LH, FSH, testosterone and corticosterone Tris-HC1, pH7.4containing1.5mm EDTA disodium measurement salt and2mm2-mercapto-ethanol (TEM buffer). The Serum LH, FSH were measured by radioimmuno- homogenate was centrifuged at 105,000 xg for60min assay employing the RIA kits supplied by Dr. at2•Ž. The supernatant fluid was concentrated using A. F. Parlow of Rat Pituitary Hormone Program, Minicon B15 (Amicon) to get an appropriate protein NIAMDD, NIH., as described previously (Waka- Vol.27, No.1 ACTION OF AA560 71 Table1. Inhibition of endogeneous androgens in mature male rats by the oral administration of AA560or chlormadinone acetate for21days. Data are shown as mean•}standard error. Animals received daily the indicated dose of AA560or chlormadinone acetate suspended in Twin80 by the oral administration for21days and were killed24hr after21th administration. * Significant difference from mean of the intact group, p<0.05. ** Significant difference from mean of the intact group, p<0.01. bayashi, 1977). The results were expressed as the FSH, LH, testosterone and corticosterone equivalent of NIH-LH-S1and NIH-FSH-S1for LH levels in mature male rats are shown in and FSH. Serum testosterone was measured by radioimmunoassayaccording to the method of Ma- Table2. In animals given daily3or9mg kino (1973). Serum corticosterone was determined of AA560there was a significant increase also by radioimmunoassay(Kanbegawa et al., 1977). of serum FSH concentration. In contrast, in animals given27mg of chlormadinone acetate the opposite was observed. Table2 Results also shows there were significant increases of serum LH and testosterone levels in ani- Effects of AA560or chlormadinone ace- mals given AA560. Chlormadinone acetate tate administration to intact male rats. did not appear to affect the serum LH level Three different doses of AA560were in these experimental conditions. The daily given orally for21days and the changes in administration of9mg of AA560increased the weights of the accessory sex organs, adrenal weights and serum corticosterone adrenal gland and testis were compared with level, whereas27mg of chlormadinone those in rats given orally chlormadinone ace- acetate significantly decreased them. tate (Table1). The ventral prostate weight Effects of the duration of AA560treat- from rats given AA560at1-9mg/head were ment in intact mature male rats. significantly less than those in the intact The effects of the duration of AA560 control rats. The seminal vesicle weights treatment in intact male rats were examined. in rats given3-9mg/head were significantly Rats received3mg of AA560suspended in less than those of the control group. Adrenal Twin80daily by gavage for1to35days. weights were significantly increased in rats The weights of ventral prostates, dorsolateral receiving daily9mg of AA560, whereas prostates and seminal vesicles were signifi- those in chlormadinone acetate treated
Load more

Recommended publications
  • Glucocorticoid Receptor Blockade Normalizes Hippocampal Alterations and Cognitive Impairment in Streptozotocin- Induced Type 1 Diabetes Mice
    Neuropsychopharmacology (2009) 34, 747–758 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org Glucocorticoid Receptor Blockade Normalizes Hippocampal Alterations and Cognitive Impairment in Streptozotocin- Induced Type 1 Diabetes Mice ,1,2 1 1 2 2 Yanina Revsin* , Niels V Rekers , Mieke C Louwe , Flavia E Saravia , Alejandro F De Nicola , 1 1 E Ron de Kloet and Melly S Oitzl 1 Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden, The Netherlands; 2 Laboratory of Neuroendocrine Biochemistry, IBYME, Buenos Aires, Argentina Type 1 diabetes is a common metabolic disorder accompanied by an increased secretion of glucocorticoids and cognitive deficits. Chronic excess of glucocorticoids per se can evoke similar neuropathological signals linked to its major target in the brain, the hippocampus. This deleterious action exerted by excess adrenal stress hormone is mediated by glucocorticoid receptors (GRs). The aim of the present study was to assess whether excessive stimulation of GR is causal to compromised neuronal viability and cognitive performance associated with the hippocampal function of the diabetic mice. For this purpose, mice had type 1 diabetes induced by streptozotocin (STZ) administration (170 mg/kg, i.p.). After 11 days, these STZ-diabetic mice showed increased glucocorticoid secretion and hippocampal alterations characterized by: (1) increased glial fibrillary acidic protein-positive astrocytes as a marker reacting to neurodegeneration, (2) increased c-Jun expression marking neuronal activation, (3) reduced Ki-67 immunostaining indicating decreased cell proliferation. At the same time, mild cognitive deficits became obvious in the novel object-placement recognition task.
    [Show full text]
  • Salivary 17 Α-Hydroxyprogesterone Enzyme Immunoassay Kit
    SALIVARY 17 α-HYDROXYPROGESTERONE ENZYME IMMUNOASSAY KIT For Research Use Only Not for use in Diagnostic Procedures Item No. 1-2602, (Single) 96-Well Kit; 1-2602-5, (5-Pack) 480 Wells Page | 1 TABLE OF CONTENTS Intended Use ................................................................................................. 3 Introduction ................................................................................................... 3 Test Principle ................................................................................................. 4 Safety Precautions ......................................................................................... 4 General Kit Use Advice .................................................................................... 5 Storage ......................................................................................................... 5 pH Indicator .................................................................................................. 5 Specimen Collection ....................................................................................... 6 Sample Handling and Preparation ................................................................... 6 Materials Supplied with Single Kit .................................................................... 7 Materials Needed But Not Supplied .................................................................. 8 Reagent Preparation ....................................................................................... 9 Procedure ...................................................................................................
    [Show full text]
  • Agonistic and Antagonistic Properties of Progesterone Metabolites at The
    European Journal of Endocrinology (2002) 146 789–800 ISSN 0804-4643 EXPERIMENTAL STUDY Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor M Quinkler, B Meyer, C Bumke-Vogt, C Grossmann, U Gruber, W Oelkers, S Diederich and V Ba¨hr Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universita¨t Berlin, Hindenburgdamm 30, 12200 Berlin, Germany (Correspondence should be addressed to M Quinkler; Email: [email protected]) Abstract Objective: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. Design: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. Methods: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. Results: Progesterone and 11b-OH-progesterone (11b-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20a-dihydro(DH)-P, 5a-DH-P and 17a-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20a-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation.
    [Show full text]
  • Pp375-430-Annex 1.Qxd
    ANNEX 1 CHEMICAL AND PHYSICAL DATA ON COMPOUNDS USED IN COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES AND HORMONAL MENOPAUSAL THERAPY Annex 1 describes the chemical and physical data, technical products, trends in produc- tion by region and uses of estrogens and progestogens in combined estrogen–progestogen contraceptives and hormonal menopausal therapy. Estrogens and progestogens are listed separately in alphabetical order. Trade names for these compounds alone and in combination are given in Annexes 2–4. Sales are listed according to the regions designated by WHO. These are: Africa: Algeria, Angola, Benin, Botswana, Burkina Faso, Burundi, Cameroon, Cape Verde, Central African Republic, Chad, Comoros, Congo, Côte d'Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia, Madagascar, Malawi, Mali, Mauritania, Mauritius, Mozambique, Namibia, Niger, Nigeria, Rwanda, Sao Tome and Principe, Senegal, Seychelles, Sierra Leone, South Africa, Swaziland, Togo, Uganda, United Republic of Tanzania, Zambia and Zimbabwe America (North): Canada, Central America (Antigua and Barbuda, Bahamas, Barbados, Belize, Costa Rica, Cuba, Dominica, El Salvador, Grenada, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago), United States of America America (South): Argentina, Bolivia, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guyana, Paraguay,
    [Show full text]
  • Canine Vascular Tissues Are Targets for Androgens, Estrogens, Progestins, and Glucocorticoids
    Canine vascular tissues are targets for androgens, estrogens, progestins, and glucocorticoids. K B Horwitz, L D Horwitz J Clin Invest. 1982;69(4):750-758. https://doi.org/10.1172/JCI110513. Research Article Sex differences and steroid hormones are known to influence the vascular system as shown by the different incidence of atherosclerosis in men and premenopausal women, or by the increased risk of cardiovascular diseases in women taking birth control pills or men taking estrogens. However, the mechanisms for these effects in vascular tissues are not known. Since steroid actions in target tissues are mediated by receptors, we have looked for cytoplasmic steroid receptor proteins in vascular tissues of dogs. We find specific saturable receptors, sedimenting at 8S on sucrose density gradients for estrogens (measured with [3H]estradiol +/- unlabeled diethylstilbestrol), androgens (measured with [3H]R1881 +/- unlabeled R1881 and triamcinolone acetonide), and glucocorticoids (measured with [3H]dexamethasone +/- unlabeled dexamethasone); they are absent for progesterone (measured with [3H]R5020 +/- unlabeled R5020 and dihydrotestosterone). Progesterone receptors can, however, be induced by 1-wk treatment of dogs with physiological estradiol concentrations (100 pg/ml serum estrogen), indicating a functional estrogen receptor. Receptor levels range from 20 to 2,000 fmol/mg DNA. They are specific for each hormone; unrelated steroids fail to complete for binding. Low dissociation constants, measured by Scatchard analyses, show that binding is of high affinity. Steroid binding sites are in the media and/or adventitia since they persist when the intima is removed. Compared with the arteries, receptor levels are reduced 80% in inferior venae cavae of […] Find the latest version: https://jci.me/110513/pdf Canine Vascular Tissues Are Targets for Androgens, Estrogens, Progestins, and Glucocorticoids KATHRYN B.
    [Show full text]
  • Chlormadinone Acetate As a Possible Effective Agent for Congenital Adrenal Hyperplasia to Suppress Elevated ACTH and Antagonize Masculinization
    Endocrine Journal 1995, 42(4), 505-508 Chlormadinone Acetate as a Possible Effective Agent for Congenital Adrenal Hyperplasia to Suppress Elevated ACTH and Antagonize Masculinization YUKIo KAGEYAMA, SATOSHIKITAHARA, TETSUROTSUKAMOTO, TOsHIHIKOTSUJII, SYUITIGOTO ANDHIROYUKI OSHIMA Department of Urology, Tokyo Medical and Dental University School of Medicine, Tokyo 113, Japan Abstract. We report two cases of congenital adrenal hyperplasia (CAH) in which administration of chlormadinone acetate (CMA), a substituted progestational agent for prostatic disease, suppressed ACTH hypersecretion and lowered plasma testosterone levels. Case 1 was 83-year-old male with advanced prostatic carcinoma and CAH due to 21-hydroxylase deficiency. His plasma testosterone did not decrease in spite of a bilateral orchiectomy. Case 2 was 40-year-old female with CAH due to 21- hydroxylase deficiency suffering from virilization after the cessation of cortisol supplement therapy because of her breast carcinoma. In these two cases, 'ral administration of CMA at a daily dose of 75- 100 mg suppressed ACTH and cortisol to subnormal levels and reduced testosterone levels. With the suppressive effect on ACTH excess and antiandrogenic action, CMA may be suitable for patients with CAH suffering from symptoms due to overproduced ACTH or adrenal androgen. Key words: Chlormadinone acetate , Congenital adrenal hyperplasia, ACTH suppression (Endocrine Journal 42: 505-508,1995) CHLORMADINONE acetate (17u-acetoxy-6-chlo- adrenal hyperplasia (CAH). Chlormadinone ace- ro-4,6-pregnadiene-3,20-dione; CMA), a substituted tate, administered for the prostatic carcinoma, progestational agent, has been used in the treat- suppressed hypersecretion of ACTH and lowered ment of benign prostatic hyperplasia (BPH) and plasma testosterone levels. With this experience prostatic carcinoma because of its anti-androgenic in mind, we administered CMA to a female pa- properties.
    [Show full text]
  • Combined Estrogen–Progestogen Menopausal Therapy
    COMBINED ESTROGEN–PROGESTOGEN MENOPAUSAL THERAPY Combined estrogen–progestogen menopausal therapy was considered by previous IARC Working Groups in 1998 and 2005 (IARC, 1999, 2007). Since that time, new data have become available, these have been incorporated into the Monograph, and taken into consideration in the present evaluation. 1. Exposure Data 1.1.2 Progestogens (a) Chlormadinone acetate Combined estrogen–progestogen meno- Chem. Abstr. Serv. Reg. No.: 302-22-7 pausal therapy involves the co-administration Chem. Abstr. Name: 17-(Acetyloxy)-6-chlo- of an estrogen and a progestogen to peri- or ropregna-4,6-diene-3,20-dione menopausal women. The use of estrogens with IUPAC Systematic Name: 6-Chloro-17-hy- progestogens has been recommended to prevent droxypregna-4,6-diene-3,20-dione, acetate the estrogen-associated risk of endometrial Synonyms: 17α-Acetoxy-6-chloro-4,6- cancer. Evidence from the Women’s Health pregnadiene-3,20-dione; 6-chloro-Δ6-17- Initiative (WHI) of adverse effects from the use acetoxyprogesterone; 6-chloro-Δ6-[17α] of a continuous combined estrogen–progestogen acetoxyprogesterone has affected prescribing. Patterns of exposure Structural and molecular formulae, and relative are also changing rapidly as the use of hormonal molecular mass therapy declines, the indications are restricted, O CH and the duration of the therapy is reduced (IARC, 3 C 2007). CH3 CH3 O C 1.1 Identification of the agents CH3 H O 1.1.1 Estrogens HH For Estrogens, see the Monograph on O Estrogen-only Menopausal Therapy in this Cl volume. C23H29ClO4 Relative molecular mass: 404.9 249 IARC MONOGRAPHS – 100A (b) Cyproterone acetate Structural and molecular formulae, and relative Chem.
    [Show full text]
  • Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds
    foods Review Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds Abigail Raffner Basson 1,2,* , Saleh Ahmed 2, Rawan Almutairi 3, Brian Seo 2 and Fabio Cominelli 1,2 1 Division of Gastroenterology & Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; [email protected] 2 Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; [email protected] (S.A.); [email protected] (B.S.) 3 Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; [email protected] * Correspondence: [email protected] Abstract: Environmental factors, particularly diet, are considered central to the pathogenesis of the inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis. In particular, the Westernization of diet, characterized by high intake of animal protein, saturated fat, and refined carbohydrates, has been shown to contribute to the development and progression of IBD. During the last decade, soybean, as well as soy-derived bioactive compounds (e.g., isoflavones, phytosterols, Bowman-Birk inhibitors) have been increasingly investigated because of their anti-inflammatory properties in animal models of IBD. Herein we provide a scoping review of the most studied disease mechanisms associated with disease induction and progression in IBD rodent models after feeding of either the whole food or a bioactive present in soybean. Keywords: inflammatory bowel disease; isoflavone; bioactive compound; isoflavones; inflammation; Crohn’s disease; western diet; plant-based Citation: Basson, A.R.; Ahmed, S.; Almutairi, R.; Seo, B.; Cominelli, F. Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds. Foods 2021, 10, 774.
    [Show full text]
  • Quantification of Hair Corticosterone, DHEA and Testosterone As
    animals Article Quantification of Hair Corticosterone, DHEA and Testosterone as a Potential Tool for Welfare Assessment in Male Laboratory Mice Alberto Elmi 1 , Viola Galligioni 2, Nadia Govoni 1 , Martina Bertocchi 1 , Camilla Aniballi 1 , Maria Laura Bacci 1 , José M. Sánchez-Morgado 2 and Domenico Ventrella 1,* 1 Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano dell’Emilia, BO, Italy; [email protected] (A.E.); [email protected] (N.G.); [email protected] (M.B.); [email protected] (C.A.); [email protected] (M.L.B.) 2 Comparative Medicine Unit, Trinity College Dublin, D02 Dublin, Ireland; [email protected] (V.G.); [email protected] (J.M.S.-M.) * Correspondence: [email protected]; Tel.: +39-051-2097-926 Received: 11 November 2020; Accepted: 14 December 2020; Published: 16 December 2020 Simple Summary: Mice is the most used species in the biomedical research laboratory setting. Scientists are constantly striving to find new tools to assess their welfare, in order to ameliorate husbandry conditions, leading to a better life and scientific data. Steroid hormones can provide information regarding different behavioral tracts of laboratory animals but their quantification often require stressful sampling procedures. Hair represents a good, less invasive, alternative in such scenario and is also indicative of longer timespan due to hormones’ accumulation. The aim of the work was to quantify steroid hormones in the hair of male laboratory mice and to look for differences imputable to age and housing conditions (pairs VS groups). Age influenced all analysed hormones by increasing testosterone and dehydroepiandrosterone (DHEA) levels and decreasing corticosterone.
    [Show full text]
  • The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats Darleen A
    The Effects of Dehydroepiandrosterone Sulfate on Counterregulatory Responses During Repeated Hypoglycemia in Conscious Normal Rats Darleen A. Sandoval, Ling Ping, Ray Anthony Neill, Sachiko Morrey, and Stephen N. Davis ␮ ⅐ ؊1 ⅐ ؊1 We previously determined that both antecedent hy- mol/l kg min ; P < 0.05). In summary, day-1 poglycemia and elevated cortisol levels blunt neu- antecedent hypoglycemia blunted neuroendocrine and roendocrine and metabolic responses to subsequent metabolic responses to next-day hypoglycemia. How- hypoglycemia in conscious, unrestrained rats. The adre- ever, simultaneous DHEA-S infusion during antecedent nal steroid dehydroepiandrosterone sulfate (DHEA-S) hypoglycemia preserved neuroendocrine and metabolic has been shown in several studies to oppose corticoste- counterregulatory responses during subsequent hypo- roid action. The purpose of this study was to determine glycemia in conscious rats. Diabetes 53:679–686, 2004 if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. he Diabetes Control and Complications Trial Day 1 consisted of two 2-h episodes of 1) hyperinsuline- mic (30 pmol ⅐ kg؊1 ⅐ min؊1) euglycemia (6.2 ؎ 0.2 established that intensive glucose control in type ANTE EUG), 2) hyperinsulinemic eug- 1 diabetic patients can slow the progression or ;12 ؍ mmol/l; n -plus simultaneous Tsignificantly reduce the onset of diabetic micro (8 ؍ lycemia (6.0 ؎ 0.1 mmol/l; n intravenous infusion of DHEA-S (30 mg/kg; ANTE EUG vascular complications (e.g., retinopathy, nephropathy, ؉ DHEA-S), 3) hyperinsulinemic hypoglycemia (2.8 ؎ neuropathy) (1). Unfortunately, the study also established ANTE HYPO), or 4) hyperinsulinemic that intensive glucose treatment causes an approximate ;12 ؍ mmol/l; n 0.1 -with simulta- threefold increase in the frequency of severe hypoglyce (8 ؍ hypoglycemia (2.8 ؎ 0.1 mmol/l; n neous intravenous infusion of DHEA-S (30 mg/kg; ANTE mia (2).
    [Show full text]
  • Plasma Corticosterone Levels in the Male Iguanid Lizard, Sceloporus Cyanogenys, Under Various Physiological Conditions
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 1971 Plasma Corticosterone Levels in the Male Iguanid Lizard, Sceloporus cyanogenys, Under Various Physiological Conditions David Reams Daugherty College of William & Mary - Arts & Sciences Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Physiology Commons Recommended Citation Daugherty, David Reams, "Plasma Corticosterone Levels in the Male Iguanid Lizard, Sceloporus cyanogenys, Under Various Physiological Conditions" (1971). Dissertations, Theses, and Masters Projects. Paper 1539624722. https://dx.doi.org/doi:10.21220/s2-jk2d-cq40 This Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. PLASMA CORTICOSTERONE LEVELS IN THE MALE IGUANID LIZARD, SCELOPORUS CYANOGENYS, UNDER VARIOUS PHYSIOLOGICAL CONDITIONS A Thesis Presented to The Faculty of the Department of Biology The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Master of Arts By David Reams Daugherty 1971 APPROVAL SHEET This thesis is submitted in partial fulfillment of the requirements for the degree of Master of Arts UT Author Approved , May 1971 Callard, Ph. D f - Robert E. L. Black, Ph. D. Jafid A. Simons, Ph. D ii S~0 4i04 -G«.~ : J lu ) ■ ACKNOWLEDGMENTS The writer wishes to express his appreciation to Professor Ian P. Callard, under whose direction this invest­ igation was conducted, for his preparation of the hypophy- sectomized and lesioned groups, and for his patient guidance and criticism throughout the investigation.
    [Show full text]
  • Progesterone Using ALZET Osmotic Pumps
    ALZET® Bibliography References on the Administration of Progesterone Using ALZET Osmotic Pumps Q8558: V. Joseph, et al. Progesterone decreases apnoea and reduces oxidative stress induced by chronic intermittent hypoxia in ovariectomized female rats. Exp Physiol 2020;105(6):1025-1034 Agents: Progesterone Vehicle: Cyclodextrin, 2-ß-Hydroxypropl-; Route: SC; Species: Rat; Pump: 2ML4; Duration: 28 days; ALZET Comments: Dose (4 mg/kg/day); Controls received mp w/ vehicle; animal info (Sprague-Dawley female rats (220-250g/57-70 days old)); post op. care (buprenorphine); Blood pressure measured via tail cuff method;93.3 mmHg - 105.2 mmHg;Progesterone aka prog; dependence; Q6232: S. F. Rosen, et al. T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice. J Neurosci 2017;37(41):9819-9827 ALZET Comments: Estradiol, 17b-; Progesterone sulfate; SC; Mice; 2002; 14 days; Dose (17b-estradiol : 0.1 mg/kg/d, progesterone sulfate: 0.25 mg/kg/d, 0.1 mg/kg/d estradiol + 0.25 mg/kg/d progesterone); Controls received mp w/ vehicle; animal info (7-12 week old female C57BL/6J mice); replacement therapy (estradiol, ovariectomy); Therapeutic indication. Q6066: D. J. Morris, et al. Glucocorticoids and gut bacteria: "The GALF Hypothesis" in the metagenomic era. Steroids 2017;125(1-13 ALZET Comments: Chenodeoxycholic acid, progesterone, 11b-hydroxy-, corticosterone, deoxy-, corticosterone, 3α,5α-TH-, progesterone, 3α,5α-TH-11β-hydroxy-; SC; Rat; steroidal derivatives of corticosterone; Review presents the role of gut microbial metabolism of endogenous adrenocorticosteroids as a contributing factor in the etiology of essential hypertension. Q6204: S. McIlvride, et al. A progesterone-brown fat axis is involved in regulating fetal growth.
    [Show full text]