Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/49791
Campo DC Valoridioma
dc.contributor.authorFernàndez, Leandroen_US
dc.contributor.authorChirino, Ricardoen_US
dc.contributor.authorBoada, Luis D.en_US
dc.contributor.authorNavarro, Domingoen_US
dc.contributor.authorCabrera, Noemíen_US
dc.contributor.authorRio, Isidoro Delen_US
dc.contributor.authorDíazchico, Bonifacio N.en_US
dc.contributor.otherDominguez-Boada, Luis-
dc.contributor.otherFernandez-Perez, Leandro-
dc.date.accessioned2018-11-24T10:44:49Z-
dc.date.available2018-11-24T10:44:49Z-
dc.date.issued1994en_US
dc.identifier.issn0013-7227en_US
dc.identifier.urihttp://hdl.handle.net/10553/49791-
dc.description.abstractSome 17 alpha-alkylated androgens used as anabolic agents, such as stanozolol (ST) and danazol (DA), have specific effects on the liver that are not exerted by testosterone. This gives rise to the possibility that a steroid-binding protein, other than the androgen receptor, could modulate the intracellular actions of these agents. Male rat liver microsomes contain a homogeneous population of [H-3]dexamethasone ([H-3]DEX)-binding sites which we have denominated low affinity glucocorticoid-binding sites (LAGS). Because glucocorticoids, progestagens, and the synthetic estrogen ethynyl estradiol compete with [H-3] DEX for binding to the LAGS, we aimed to study the possible interactions between androgens and the LAGS. To investigate whether several androgens had the capability of interacting with the LAGS, we performed competition experiments. The LAGS had no affinity for testosterone or methyltrienolone (R1881). However, some 17 alpha-alkylated androgens (DA (IC50, 116 nM) > ST much greater than fluoxymesterone > mestaline > methandriol much greater than methandrostenolone > methyltestosterone) were able to compete with [H-3]DEX binding to liver microsomes. ST and DA were potent inhibitors of [H-3]DEX binding to liver microsomes. They decreased both the affinity and the number of [H-3]DEX-binding sites, increased the dissociation rate of [H-3]DEX from the LAGS, and provoked a time- and dose-dependent inactivation of the [H-3]DEX-binding site. These results strongly suggest that ST and DA exert a negative allosteric modulation on [H-3]DEX binding to the LAGS. The in vivo administration of ST (but not other androgens) to male rats provoked a time- and dose-dependent decrease in the LAGS level. Full recovery of the LAGS concentration required at least 8 h and was blocked by protein synthesis inhibitors. Such results suggest that ST irreversibly inactivates the [H-3]DEX-binding site in vivo as it does in vitro.Taken together, these observations are indicative of an irreversible interaction between some 17 alpha-alkylated androgens and the LAGS both in vitro and in vivo and suggest that ST may be an important pharmacological tool that can be used in the elucidation of the molecular structure of the LAGS. These results also mean that the LAGS are a steroid-binding entity able to distinguish between natural androgens and 17 alpha-alkylated testosterone derivatives used as anabolic agents.en_US
dc.languageengen_US
dc.relation.ispartofEndocrinology (Philadelphia)en_US
dc.sourceEndocrinology[ISSN 0013-7227],v. 134, p. 1401-1408en_US
dc.subject32 Ciencias médicasen_US
dc.subject320502 Endocrinologíaen_US
dc.subject.otherDexamethasone-Bindingen_US
dc.subject.otherRadioligand Bindingen_US
dc.subject.otherEstrogen-Receptorsen_US
dc.subject.otherAnabolic Steroidsen_US
dc.subject.otherNuclear Envelopesen_US
dc.subject.otherPlasma-Membranesen_US
dc.subject.otherCytochrome-P-450en_US
dc.subject.otherInvitroen_US
dc.subject.otherProgesteroneen_US
dc.subject.otherFractionsen_US
dc.titleStanozolol and danazol, unlike natural androgens, interact with the low affinity glucocorticoid-binding sites from male rat liver microsomesen_US
dc.typeinfo:eu-repo/semantics/Articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1210/endo.134.3.8119180en_US
dc.identifier.scopus0028328702-
dc.identifier.isiA1994MZ44300056-
dcterms.isPartOfEndocrinology-
dcterms.sourceEndocrinology[ISSN 0013-7227],v. 134 (3), p. 1401-1408-
dc.contributor.authorscopusid7202848203-
dc.contributor.authorscopusid6701324062-
dc.contributor.authorscopusid6603916807-
dc.contributor.authorscopusid7004873659-
dc.contributor.authorscopusid7003694022-
dc.contributor.authorscopusid57192002662-
dc.contributor.authorscopusid57192003937-
dc.description.lastpage1408en_US
dc.identifier.issue3-
dc.description.firstpage1401en_US
dc.relation.volume134en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.identifier.wosWOS:A1994MZ44300056-
dc.contributor.daisngid795544-
dc.contributor.daisngid880609-
dc.contributor.daisngid697526-
dc.contributor.daisngid359684-
dc.contributor.daisngid4106512-
dc.contributor.daisngid32185230-
dc.contributor.daisngid14517264-
dc.contributor.daisngid30778603-
dc.contributor.daisngid301761-
dc.contributor.daisngid1724161-
dc.identifier.investigatorRIDL-5577-2015-
dc.identifier.investigatorRIDH-1493-2015-
dc.description.numberofpages8en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:FERNANDEZ, L-
dc.contributor.wosstandardWOS:CHIRINO, R-
dc.contributor.wosstandardWOS:BOADA, LD-
dc.contributor.wosstandardWOS:NAVARRO, D-
dc.contributor.wosstandardWOS:CABRERA, N-
dc.contributor.wosstandardWOS:DELRIO, I-
dc.contributor.wosstandardWOS:DIAZCHICO, BN-
dc.date.coverdateEnero 1994en_US
dc.identifier.ulpgcen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.scieSCIE-
item.grantfulltextnone-
item.fulltextSin texto completo-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.deptGIR IUIBS: Diabetes y endocrinología aplicada-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología-
crisitem.author.deptGIR IUIBS: Medio Ambiente y Salud-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.deptGIR IUIBS: Bioquímica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Bioquímica y Biología Molecular, Fisiología, Genética e Inmunología-
crisitem.author.orcid0000-0001-7802-465X-
crisitem.author.orcid0000-0002-5681-8931-
crisitem.author.orcid0000-0002-0195-4565-
crisitem.author.orcid0000-0002-0944-990X-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameFernández Pérez, Leandro Francisco-
crisitem.author.fullNameChirino Godoy, Ricardo-
crisitem.author.fullNameDomínguez Boada, Luis María-
crisitem.author.fullNameDíaz Chico, Juan Carlos-
Colección:Artículos
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