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Pesquisa : D04.210.500.745.745.654.829.100 [Categoria DeCS]
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[PMID]:28167298
[Au] Autor:Cermenati G; Giatti S; Audano M; Pesaresi M; Spezzano R; Caruso D; Mitro N; Melcangi RC
[Ad] Endereço:Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy.
[Ti] Título:Diabetes alters myelin lipid profile in rat cerebral cortex: Protective effects of dihydroprogesterone.
[So] Source:J Steroid Biochem Mol Biol;168:60-70, 2017 Apr.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Due to the emerging association of diabetes with several psychiatric and neurodegenerative events, the evaluation of the effects of this pathology on the brain function has now a high priority in biomedical research. In particular, the effects of diabetes on myelin compartment have been poorly taken into consideration. To this purpose, we performed a deep lipidomic analysis of cortical myelin in the streptozotocin-induced diabetic rat model. In male rats three months of diabetes induced an extensive alterations in levels of phosphatidylcholines and phosphatidylethanolamines (the main species present in myelin membranes), plasmalogens as well as phosphatidylinositols and phosphatidylserines. In addition, the levels of cholesterol and myelin basic protein were also decreased. Because these lipids exert important functional and structural roles in the myelin compartment, our data indicate that cerebral cortex myelin is severely compromised in diabetic status. Treatment for one-month with a metabolite of progesterone, dihydroprogesterone, restored the lipid and protein myelin profiles to the levels observed in non-diabetic animals. These data suggest the potential of therapeutic efficacy of DHP to restore myelin in the diabetic brain.
[Mh] Termos MeSH primário: 20-alfa-Di-Hidroprogesterona/farmacologia
Córtex Cerebral/metabolismo
Diabetes Mellitus Experimental/metabolismo
Lipídeos/química
Bainha de Mielina/metabolismo
[Mh] Termos MeSH secundário: Animais
Colesterol/química
Cromatografia Líquida
Cromatografia Gasosa-Espectrometria de Massas
Perfilação da Expressão Gênica
Masculino
Proteína Básica da Mielina/metabolismo
Fosfatidilinositóis/química
Fosfatidilserinas/química
Progesterona/metabolismo
Ratos
Ratos Sprague-Dawley
Nervo Isquiático/metabolismo
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipids); 0 (Myelin Basic Protein); 0 (Phosphatidylinositols); 0 (Phosphatidylserines); 145-14-2 (20-alpha-Dihydroprogesterone); 4G7DS2Q64Y (Progesterone); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170208
[St] Status:MEDLINE


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[PMID]:27220236
[Au] Autor:Bayunova LV
[Ti] Título:[THE EFFECT OF HORMONAL STIMULATION OF STERLET (ACIPENSER RUTHENUS L.) ON STEROID LEVELS IN TISSUE INCUBATES].
[So] Source:Zh Evol Biokhim Fiziol;52(1):17-25, 2016 Jan-Feb.
[Is] ISSN:0044-4529
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Sex steroids and corticol levels in Leibovitz's L-15 media samples after incubation of intact female and male sterlet (Acipenser rhutenus L.) tissue fragments and those if fishes treated with a superactive analogue of mammalian luteinising hormone-releasing hormone (LH-RH-A) were compared. 17,20ß,21-trihydroxy-4-pregnen-3-one (20ßS) levels were significantly higher in the media samples after incubation of ovarian follicles taken from females 5 h after treatment with LH-RH-A in comparison with 20ßS levels in intact female samples. 20ßS levels also increased after 1 µM progesterone (P4) adding to the media before incubation of ovarian follicles. Cortisol and testosterone levels in the media samples demonstrated the same tendency. Significant elevation of cortisol levels was observed in the blood serum samples of females 5 h after LH-RH-A treatment. The androgens (testosterone and 11-ketotestosterone) levels after incubation of testicular and liver fragments were high in the media samples in males who had high serum levels of these androgens before hormonal stimulation. Sex steroids and cortisol production was stimulated by P4 adding to the media before incubation of gonad fragments. 20ßS media levels increased after P4 adding before incubation of liver fragments.
[Mh] Termos MeSH primário: Peixes/metabolismo
Hidrocortisona/metabolismo
Hormônio Luteinizante/farmacologia
Progestinas/farmacologia
Testosterona/metabolismo
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/farmacologia
Animais
Feminino
Gônadas/efeitos dos fármacos
Gônadas/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Oócitos/efeitos dos fármacos
Oócitos/metabolismo
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Progestins); 145-14-2 (20-alpha-Dihydroprogesterone); 3XMK78S47O (Testosterone); 9002-67-9 (Luteinizing Hormone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:160525
[Lr] Data última revisão:
160525
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160526
[St] Status:MEDLINE


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[PMID]:27209438
[Au] Autor:Deligiannidis KM; Kroll-Desrosiers AR; Mo S; Nguyen HP; Svenson A; Jaitly N; Hall JE; Barton BA; Rothschild AJ; Shaffer SA
[Ad] Endereço:Center for Psychopharmacologic Research & Treatment, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA 01655, USA; Women's Mental Health Program, Departments of Psychiatry and Obstetrics & Gynecology, University of Massachusetts Medical School, UMass Memoria
[Ti] Título:Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression.
[So] Source:Psychoneuroendocrinology;70:98-107, 2016 Aug.
[Is] ISSN:1873-3360
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neuroactive steroids (NAS) are allosteric modulators of the γ-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9±0.7ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8±7.5 (p=0.04) and 1.5±0.7ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (ß=-0.14±0.05, p=0.01) and positively associated with pregnanolone (ß=0.16±0.06, p=0.01). STAI-S was positively associated with pregnanolone (ß=0.11±0.04, p=0.004), allopregnanolone (ß=0.13±0.05, p=0.006) and pregnenolone (ß=0.02±0.01, p=0.04). HAM-A was negatively associated with GABA (ß=-0.12±0.04, p=0.004) and positively associated with pregnanolone (ß=0.11±0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.
[Mh] Termos MeSH primário: Depressão Pós-Parto/sangue
Esteroides/sangue
Ácido gama-Aminobutírico/sangue
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/sangue
Adulto
Estudos de Casos e Controles
Desoxicorticosterona/sangue
Feminino
Seres Humanos
Estudos Longitudinais
Período Periparto/fisiologia
Período Periparto/psicologia
Gravidez
Pregnanolona/sangue
Progesterona/sangue
Receptores de GABA-A/sangue
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, GABA-A); 0 (Steroids); 145-14-2 (20-alpha-Dihydroprogesterone); 40GP35YQ49 (Desoxycorticosterone); 4G7DS2Q64Y (Progesterone); 56-12-2 (gamma-Aminobutyric Acid); BXO86P3XXW (Pregnanolone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160523
[St] Status:MEDLINE


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[PMID]:26814209
[Au] Autor:Legacki EL; Scholtz EL; Ball BA; Stanley SD; Berger T; Conley AJ
[Ti] Título:The dynamic steroid landscape of equine pregnancy mapped by mass spectrometry.
[So] Source:Reproduction;151(4):421-30, 2016 Apr.
[Is] ISSN:1741-7899
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allowed comprehensive analysis of various steroids detectable in plasma throughout equine gestation. Mares (n=9) were bled serially until they foaled. Certain steroids dominated the profile at different stages of gestation, clearly defining key physiological and developmental transitions. The period (weeks 6-20) coincident with equine chorionic gonadotropic (eCG) stimulation of primary corpora lutea and subsequent formation of secondary luteal structures was defined by increased progesterone, 17OH-progesterone and androstenedione, all Δ4 steroids. The 5α-reduced metabolite of progesterone, dihydroprogesterone (DHP) paralleled progesterone secretion at less than half the concentration until week 12 of gestation when progesterone began to decline but DHP concentrations continued to increase. DHP exceeded progesterone concentrations by week 16, clearly defining the luteo-placental shift in pregnane synthesis from primarily ovarian to primarily placental. The period corresponding to the growth of fetal gonads was defined by increasing dehydroepiandrosterone and pregnenolone (Δ5 steroids) concentrations from week 14, peaking at week 34 and declining to term. Metabolites of DHP (including allopregnanolone) dominated the steroid profile in late gestation, some exceeding DHP by weeks 13 or 14 and near term by almost tenfold. Thus Δ4 steroids dominated during ovarian stimulation by eCG, inversion of the ratio of progesterone: DHP (increasing 5α-pregnanes) marked the luteo-placental shift, Δ5 steroids defined fetal gonadal growth and 5α-reduced metabolites of DHP dominated the steroid profile in mid- to late-gestation. Comprehensive LC-MS/MS steroid analysis provides opportunities to better monitor the physiology and the progress of equine pregnancies, including fetal development.
[Mh] Termos MeSH primário: Corpo Lúteo/metabolismo
Placenta/metabolismo
Prenhez
Esteroides/metabolismo
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/metabolismo
Animais
Biomarcadores/metabolismo
Cromatografia Líquida
Feminino
Cavalos
Gravidez
Pregnanolona/metabolismo
Pregnenolona/metabolismo
Progesterona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Steroids); 145-14-2 (20-alpha-Dihydroprogesterone); 4G7DS2Q64Y (Progesterone); 73R90F7MQ8 (Pregnenolone); BXO86P3XXW (Pregnanolone)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160128
[St] Status:MEDLINE
[do] DOI:10.1530/REP-15-0547


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[PMID]:25785994
[Au] Autor:do Rego JL; Vaudry D; Vaudry H
[Ad] Endereço:Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France; Regional Platform for Cell Imaging (PRIMACEN), International Associated Laboratory Samuel de Champlain, University of Rouen, Mont-Saint-Aignan, France.
[Ti] Título:The non-benzodiazepine anxiolytic drug etifoxine causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis.
[So] Source:PLoS One;10(3):e0120473, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neurosteroids can modulate the activity of the GABAA receptors, and thus affect anxiety-like behaviors. The non-benzodiazepine anxiolytic compound etifoxine has been shown to increase neurosteroid concentrations in brain tissue but the mode of action of etifoxine on neurosteroid formation has not yet been elucidated. In the present study, we have thus investigated the effect and the mechanism of action of etifoxine on neurosteroid biosynthesis using the frog hypothalamus as an experimental model. Exposure of frog hypothalamic explants to graded concentrations of etifoxine produced a dose-dependent increase in the biosynthesis of 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone and tetrahydroprogesterone, associated with a decrease in the production of dihydroprogesterone. Time-course experiments revealed that a 15-min incubation of hypothalamic explants with etifoxine was sufficient to induce a robust increase in neurosteroid synthesis, suggesting that etifoxine activates steroidogenic enzymes at a post-translational level. Etifoxine-evoked neurosteroid biosynthesis was not affected by the central-type benzodiazepine (CBR) receptor antagonist flumazenil, the translocator protein (TSPO) antagonist PK11195 or the GABAA receptor antagonist bicuculline. In addition, the stimulatory effects of etifoxine and the triakontatetraneuropeptide TTN, a TSPO agonist, were additive, indicating that these two compounds act through distinct mechanisms. Etifoxine also induced a rapid stimulation of neurosteroid biosynthesis from frog hypothalamus homogenates, a preparation in which membrane receptor signalling is disrupted. In conclusion, the present study demonstrates that etifoxine stimulates neurosteroid production through a membrane receptor-independent mechanism.
[Mh] Termos MeSH primário: 17-alfa-Hidroxipregnenolona/agonistas
Ansiolíticos/farmacologia
Desidroepiandrosterona/agonistas
Hipotálamo/efeitos dos fármacos
Oxazinas/farmacologia
Pregnanolona/agonistas
Progesterona/agonistas
[Mh] Termos MeSH secundário: 17-alfa-Hidroxipregnenolona/metabolismo
20-alfa-Di-Hidroprogesterona/antagonistas & inibidores
20-alfa-Di-Hidroprogesterona/biossíntese
Animais
Bicuculina/farmacologia
Misturas Complexas/química
Desidroepiandrosterona/biossíntese
Relação Dose-Resposta a Droga
Flumazenil/farmacologia
Moduladores GABAérgicos/farmacologia
Antagonistas de Receptores de GABA-A/farmacologia
Expressão Gênica
Hipotálamo/metabolismo
Isoquinolinas/farmacologia
Masculino
Neuropeptídeos/farmacologia
Fragmentos de Peptídeos/farmacologia
Pregnanolona/biossíntese
Progesterona/biossíntese
Rana esculenta
Receptores de GABA-A/genética
Receptores de GABA-A/metabolismo
Técnicas de Cultura de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Complex Mixtures); 0 (GABA Modulators); 0 (GABA-A Receptor Antagonists); 0 (Isoquinolines); 0 (Neuropeptides); 0 (Oxazines); 0 (Peptide Fragments); 0 (Receptors, GABA-A); 120667-90-5 (triakontatetraneuropeptide); 145-14-2 (20-alpha-Dihydroprogesterone); 387-79-1 (17-alpha-Hydroxypregnenolone); 40P7XK9392 (Flumazenil); 459AG36T1B (Dehydroepiandrosterone); 4G7DS2Q64Y (Progesterone); BXO86P3XXW (Pregnanolone); X24X82MX4X (etifoxine); Y37615DVKC (Bicuculline); YNF83VN1RL (PK 11195)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150319
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0120473


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[PMID]:24717976
[Au] Autor:Caruso D; Abbiati F; Giatti S; Romano S; Fusco L; Cavaletti G; Melcangi RC
[Ad] Endereço:Department of Pharmacological and Biomolecular Sciences - Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.
[Ti] Título:Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma.
[So] Source:J Steroid Biochem Mol Biol;146:74-9, 2015 Feb.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolism of progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography-tandem mass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in CSF showed a decrease of PROG and its metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), associated with an increase of its precursor pregnenolone (PREG). Altered levels were also observed for T and its metabolites. Thus, a significant decrease of dihydrotestosterone (DHT) associated with an increase of T as well as of 3α-diol was detected. Changes in neuroactive steroid levels also occurred in plasma. An increase of PREG, T, 3α-diol, 3ß-diol and 17ß-estradiol was associated with decreased levels of DHP and THP. The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment. This article is part of a Special Issue entitled 'Sex steroids and brain disorders'.
[Mh] Termos MeSH primário: Alopecia/tratamento farmacológico
Depressão/induzido quimicamente
Finasterida/efeitos adversos
Esteroides/sangue
Esteroides/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/sangue
20-alfa-Di-Hidroprogesterona/líquido cefalorraquidiano
Adulto
Transtornos de Ansiedade/induzido quimicamente
Transtornos de Ansiedade/metabolismo
Estudos de Casos e Controles
Depressão/sangue
Finasterida/uso terapêutico
Seres Humanos
Masculino
Pregnenolona/sangue
Pregnenolona/líquido cefalorraquidiano
Progesterona/sangue
Progesterona/líquido cefalorraquidiano
Disfunções Sexuais Psicogênicas/sangue
Disfunções Sexuais Psicogênicas/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Steroids); 145-14-2 (20-alpha-Dihydroprogesterone); 4G7DS2Q64Y (Progesterone); 57GNO57U7G (Finasteride); 73R90F7MQ8 (Pregnenolone)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:141219
[Lr] Data última revisão:
141219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140411
[St] Status:MEDLINE


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[PMID]:24992790
[Au] Autor:Warenik-Szymankiewicz A; Slopien R
[Ti] Título:Pregnancy in a patient with premature ovarian failure.
[So] Source:Clin Exp Obstet Gynecol;41(3):341-2, 2014.
[Is] ISSN:0390-6663
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Premature ovarian failure (POF) occurs in about one in 100 women under 40 years of age. The authors report a case of a POF patient who conceived during hormonal replacement therapy (HRT). CASE: A 24-year-old woman with confirmed POF conceived spontaneously during HRT. CONCLUSION: Pregnancy is possible in women with POF.
[Mh] Termos MeSH primário: Terapia de Reposição Hormonal
Complicações na Gravidez/tratamento farmacológico
Insuficiência Ovariana Primária/tratamento farmacológico
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/uso terapêutico
Estradiol/uso terapêutico
Estrogênios/uso terapêutico
Feminino
Seres Humanos
Nascimento Vivo
Gravidez
Resultado da Gravidez
Progestinas/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Estrogens); 0 (Progestins); 145-14-2 (20-alpha-Dihydroprogesterone); 4TI98Z838E (Estradiol)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:140704
[Lr] Data última revisão:
140704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140705
[St] Status:MEDLINE


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[PMID]:24818306
[Ti] Título:Pregnancy hormone mystery solved.
[So] Source:J Am Vet Med Assoc;244(8):887, 2014 Apr 15.
[Is] ISSN:1943-569X
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: 20-alfa-Di-Hidroprogesterona/fisiologia
Cavalos/fisiologia
Prenhez
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/sangue
20-alfa-Di-Hidroprogesterona/metabolismo
Animais
Feminino
Gravidez
Prenhez/fisiologia
[Pt] Tipo de publicação:NEWS
[Nm] Nome de substância:
145-14-2 (20-alpha-Dihydroprogesterone)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:140512
[Lr] Data última revisão:
140512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140514
[St] Status:MEDLINE


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[PMID]:24607810
[Au] Autor:Mitro N; Cermenati G; Brioschi E; Abbiati F; Audano M; Giatti S; Crestani M; De Fabiani E; Azcoitia I; Garcia-Segura LM; Caruso D; Melcangi RC
[Ad] Endereço:Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, Italy.
[Ti] Título:Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.
[So] Source:J Steroid Biochem Mol Biol;143:115-21, 2014 Sep.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5α-androstane-3α,17ß-diol (3α-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3α-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3α-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3α-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile.
[Mh] Termos MeSH primário: 20-alfa-Di-Hidroprogesterona/farmacologia
Androstano-3,17-diol/farmacologia
Neuropatias Diabéticas/metabolismo
Lipídeos/análise
Bainha de Mielina/metabolismo
Doenças do Sistema Nervoso Periférico/metabolismo
Nervo Isquiático/metabolismo
[Mh] Termos MeSH secundário: Anabolizantes/farmacologia
Animais
Biomarcadores/análise
Cromatografia Líquida
Diabetes Mellitus Experimental/complicações
Neuropatias Diabéticas/tratamento farmacológico
Neuropatias Diabéticas/etiologia
Masculino
Bainha de Mielina/efeitos dos fármacos
Doenças do Sistema Nervoso Periférico/tratamento farmacológico
Doenças do Sistema Nervoso Periférico/etiologia
Progestinas/farmacologia
RNA Mensageiro/genética
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Nervo Isquiático/efeitos dos fármacos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anabolic Agents); 0 (Biomarkers); 0 (Lipids); 0 (Progestins); 0 (RNA, Messenger); 145-14-2 (20-alpha-Dihydroprogesterone); 25126-76-5 (Androstane-3,17-diol)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140311
[St] Status:MEDLINE


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[PMID]:24492656
[Au] Autor:Kozai K; Hojo T; Tokuyama S; Szóstek AZ; Takahashi M; Sakatani M; Nambo Y; Skarzynski DJ; Okuda K
[Ad] Endereço:Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan.
[Ti] Título:Expression of aldo-keto reductase 1C23 in the equine corpus luteum in different luteal phases.
[So] Source:J Reprod Dev;60(2):150-4, 2014 Apr 24.
[Is] ISSN:1348-4400
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated with functional luteolysis in mares, we investigated the expression of AKR1C23 in the CL in different luteal phases. The luteal P4 concentration and levels of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA were higher in the mid luteal phase than in the late and regressed luteal phases (P<0.05), but the level of 3ß-HSD protein was higher in the late luteal phase than in the regressed luteal phase (P<0.05). The luteal 20α-OHP concentration and the level of AKR1C23 mRNA were higher in the late luteal phase than in the early and mid luteal phases (P<0.05), and the level of AKR1C23 protein was also highest in the late luteal phase. Taken together, these findings suggest that metabolism of P4 by AKR1C23 is one of the processes contributing to functional luteolysis in mares.
[Mh] Termos MeSH primário: Aldeído Redutase/biossíntese
Corpo Lúteo/enzimologia
Cavalos/metabolismo
Fase Luteal/metabolismo
Luteólise/fisiologia
[Mh] Termos MeSH secundário: 20-alfa-Di-Hidroprogesterona/biossíntese
20-alfa-Di-Hidroprogesterona/genética
3-Hidroxiesteroide Desidrogenases/biossíntese
3-Hidroxiesteroide Desidrogenases/genética
Aldeído Redutase/genética
Aldo-Ceto Redutases
Animais
Western Blotting
Feminino
Regulação Enzimológica da Expressão Gênica
Progesterona/biossíntese
Progesterona/genética
RNA/química
RNA/genética
Reação em Cadeia da Polimerase em Tempo Real/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
145-14-2 (20-alpha-Dihydroprogesterone); 4G7DS2Q64Y (Progesterone); 63231-63-0 (RNA); EC 1.1.- (3-Hydroxysteroid Dehydrogenases); EC 1.1.1.- (Aldo-Keto Reductases); EC 1.1.1.21 (Aldehyde Reductase)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140205
[St] Status:MEDLINE



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