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[PMID]:29331373
[Au] Autor:Kwack MH; Yang JM; Won GH; Kim MK; Kim JC; Sung YK
[Ad] Endereço:Department of Immunology, School of Medicine, Kyungpook National University, Daegu, South Korea.
[Ti] Título:Establishment and characterization of five immortalized human scalp dermal papilla cell lines.
[So] Source:Biochem Biophys Res Commun;496(2):346-351, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured DP cells are useful for the study of their role in relation to hair growth and regeneration. However, cultivation of human DP cells is tedious and difficult. In addition, cultured DP cells possess a relatively short replicative life span, requiring immortalized human DP cell lines. We previously established an immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC. In this study, we co-transfected the simian virus 40 large T antigen (SV40T-Ag) and hTERT into DP cells from scalp hair follicles from a male with androgenetic alopecia and established five immortalized DP cell lines and named KNU-101, KNU-102, KNU-103, KNU-201 and KNU-202. We then evaluated tumorigenicity, expression of DP markers, responses to androgen, Wnt3a and BMP4, and expression of DP signature genes. These cell lines displayed early passage morphology and maintained responses to androgen, Wnt and BMP. Furthermore, these cell lines expressed DP markers and DP signature genes. KNU cell lines established in this study are potentially useful sources for hair research.
[Mh] Termos MeSH primário: Alopecia/genética
Derme/metabolismo
Efeito Fundador
Folículo Piloso/metabolismo
[Mh] Termos MeSH secundário: Células A549
Alopecia/metabolismo
Alopecia/patologia
Animais
Biglicano/genética
Biglicano/metabolismo
Biomarcadores/metabolismo
Proteína Morfogenética Óssea 4/farmacologia
Carcinogênese/genética
Carcinogênese/metabolismo
Carcinogênese/patologia
Linhagem Celular Transformada
Derme/patologia
Di-Hidrotestosterona/farmacologia
Feminino
Expressão Gênica
Folículo Piloso/efeitos dos fármacos
Folículo Piloso/patologia
Seres Humanos
Queratina-8/genética
Queratina-8/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Receptores Androgênicos/genética
Receptores Androgênicos/metabolismo
Couro Cabeludo/metabolismo
Couro Cabeludo/patologia
Versicanas/genética
Versicanas/metabolismo
Proteína Wnt3A/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (BGN protein, human); 0 (BMP4 protein, human); 0 (Biglycan); 0 (Biomarkers); 0 (Bone Morphogenetic Protein 4); 0 (KRT8 protein, human); 0 (Keratin-8); 0 (Receptors, Androgen); 0 (VCAN protein, human); 0 (WNT3A protein, human); 0 (Wnt3A Protein); 08J2K08A3Y (Dihydrotestosterone); 126968-45-4 (Versicans)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:29176856
[Au] Autor:Huber SE; Lenz B; Kornhuber J; Müller CP
[Ad] Endereço:Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
[Ti] Título:Prenatal androgen-receptor activity has organizational morphological effects in mice.
[So] Source:PLoS One;12(11):e0188752, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prenatal sex hormones exert organizational effects. It has been suggested that prenatal sex hormones affect adult morphological parameters, such as the finger length. Especially the second-to-fourth finger length (2D:4D) ratio has been implicated to be modified when exposed to higher androgen levels in utero. Here we show in a mouse model that experimental manipulation of the prenatal androgen level, by blocking the androgen receptor with flutamide or activating the androgen receptor with dihydrotestosterone (DHT), leads to changes in the length of the fingers of all paws in males and females. In addition to that, also total paw length and the 2D:4D ratio was affected. In males treated with DHT, the 2D:4D ratio was increased, while flutamide-treatment in females led to a reduced 2D:4D ratio. We also measured other parameters, such as head size, body length and tail length and demonstrate that body morphology is affected by prenatal androgen exposure with more prominent effects in females. Another factor that is thought to be influenced by early androgens is handedness. We tested mice for handedness, but did not find a significant effect of the prenatal treatment. These findings demonstrate that prenatal androgen activity is involved in the development of body morphology and might be a useful marker for prenatal androgen exposure.
[Mh] Termos MeSH primário: Extremidades/anatomia & histologia
Efeitos Tardios da Exposição Pré-Natal/metabolismo
Receptores Androgênicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Tamanho Corporal
Di-Hidrotestosterona/farmacologia
Feminino
Flutamida/farmacologia
Lateralidade Funcional/efeitos dos fármacos
Hormônios Esteroides Gonadais/metabolismo
Masculino
Camundongos
Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gonadal Steroid Hormones); 0 (Receptors, Androgen); 08J2K08A3Y (Dihydrotestosterone); 76W6J0943E (Flutamide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188752


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[PMID]:28457967
[Au] Autor:Araya S; Kratschmar DV; Tsachaki M; Stücheli S; Beck KR; Odermatt A
[Ad] Endereço:Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
[Ti] Título:DHRS7 (SDR34C1) - A new player in the regulation of androgen receptor function by inactivation of 5α-dihydrotestosterone?
[So] Source:J Steroid Biochem Mol Biol;171:288-295, 2017 07.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DHRS7 (SDR34C1) has been associated with potential tumor suppressor effects in prostate cancer; however, its function remains largely unknown. Recent experiments using purified recombinant human DHRS7 suggested several potential substrates, including the steroids cortisone and Δ4-androstene-3,17-dione (androstenedione). However, the substrate and cofactor concentrations used in these experiments were very high and the physiological relevance of these observations needed to be further investigated. In the present study, recombinant human DHRS7 was expressed in intact HEK-293 cells in order to investigate whether glucocorticoids and androgens serve as substrates at sub-micromolar concentrations and at physiological cofactor concentrations. Furthermore, the membrane topology of DHRS7 was revisited using redox-sensitive green-fluorescent protein fusions in living cells. The results revealed that (1) cortisone is a substrate of DHRS7; however, it is not reduced to cortisol but to 20ß-dihydrocortisone, (2) androstenedione is not a relevant substrate of DHRS7, (3) DHRS7 catalyzes the oxoreduction of 5α-dihydrotestosterone (5αDHT) to 3α-androstanediol (3αAdiol), with a suppressive effect on androgen receptor (AR) transcriptional activity, and (4) DHRS7 is anchored in the endoplasmic reticulum membrane with a cytoplasmic orientation. Together, the results show that DHRS7 is a cytoplasmic oriented enzyme exhibiting 3α/20ß-hydroxysteroid dehydrogenase activity, with a possible role in the modulation of AR function. Further research needs to address the physiological relevance of DHRS7 in the inactivation of 5αDHT and AR regulation.
[Mh] Termos MeSH primário: Androgênios/metabolismo
Di-Hidrotestosterona/metabolismo
Regulação para Baixo
Retículo Endoplasmático/enzimologia
Oxirredutases/metabolismo
Receptores Androgênicos/metabolismo
[Mh] Termos MeSH secundário: Androgênios/química
Androstano-3,17-diol/química
Androstano-3,17-diol/metabolismo
Cortisona/análogos & derivados
Cortisona/química
Cortisona/metabolismo
Di-Hidrotestosterona/química
Glucocorticoides/metabolismo
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Células HEK293
Seres Humanos
Ligantes
Conformação Molecular
Oligopeptídeos/genética
Oligopeptídeos/metabolismo
Concentração Osmolar
Oxirredução
Oxirredutases/química
Oxirredutases/genética
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Transporte Proteico
Receptores Androgênicos/química
Receptores Androgênicos/genética
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AR protein, human); 0 (Androgens); 0 (Glucocorticoids); 0 (Ligands); 0 (Oligopeptides); 0 (Peptide Fragments); 0 (Receptors, Androgen); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 08J2K08A3Y (Dihydrotestosterone); 147336-22-9 (Green Fluorescent Proteins); 25126-76-5 (Androstane-3,17-diol); 3615-87-0 (4-pregnene-17 alpha,20 beta,21-triol-3,11-dione); 98849-88-8 (FLAG peptide); EC 1.- (DHRS7 protein, human); EC 1.- (Oxidoreductases); V27W9254FZ (Cortisone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29031687
[Au] Autor:Pham JH; Will CM; Mack VL; Halbert M; Conner EA; Bucholtz KM; Thomas JL
[Ad] Endereço:Department of Biomedical Sciences, Macon, GA, 31207, USA.
[Ti] Título:Structure-function relationships for the selective inhibition of human 3ß-hydroxysteroid dehydrogenase type 1 by a novel androgen analog.
[So] Source:J Steroid Biochem Mol Biol;174:257-264, 2017 Nov.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:3ß-Hydroxysteroid dehydrogenase type 1 (3ß-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3ß-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3ß-HSD1 (Ser194, Arg195) and 3ß-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3ß-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano-17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from androstenedione. In purified 3ß-HSD inhibition studies, DiCN-AND competitively inhibited 3ß- HSD1 with K =4.7µM and noncompetitively inhibited 3ß-HSD2 with a 6.5-fold higher K =30.7µM. We previously reported similar isoenzyme-specific inhibition profiles for trilostane. Based on our docking results, we created, expressed and purified the chimeric S194G-1 mutant of 3ß-HSD1. Trilostane inhibited S194G-1 (K =0.67µM) with a noncompetitive mode compared to its 6.7-fold higher affinity, competitive inhibition of 3ß-HSD1 (K =0.10µM). DiCN-AND inhibited S194G-1 with a 6.3-fold higher K (29.5µM) than measured for 3ß-HSD1 (K =4.7µM) but with the same competitive mode for both enzyme species. Since DiCN-AND noncompetitively inhibits 3ß-HSD2, which has the Gly194 and Pro195 of 3ß-HSD2 in place of the Ser194 and Arg195 in 3ß-HSD1, this suggests that Arg195 alone in 3ß-HSD1 or S194G-1 is required to bind DiCN-AND in the substrate binding site (competitive inhibition). However, both Ser194 and Arg195 are required to bind trilostane in the 3ß-HSD1 substrate site based on its noncompetitive inhibition of S194G-1 and 3ß-HSD2. In support of this hypothesis, DiCN-AND inhibited our chimeric R195P-1 mutant noncompetitively with a K =41.3µM (similar to the 3ß-HSD2 inhibition profile). Since DiCN-AND competitively inhibited S194G-1 that still contains R195 but noncompetitively inhibited R195P-1 that still contains S194, our data provides strong evidence that the Arg195 being mutated to Pro195 (as present in 3ß-HSD2) shifts the inhibition mode from competitive to noncompetitive in 3ß-HSD1. This supports the key role of Arg195 in 3ß-HSD1 for the high affinity, competitive binding of the trilostane analogs. Our new structure/function information for the design of targeted 3ß-HSD1 inhibitors may lead to important new treatments for the prevention of spontaneous premature birth.
[Mh] Termos MeSH primário: 3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores
3-Hidroxiesteroide Desidrogenases/metabolismo
Arginina/metabolismo
Di-Hidrotestosterona/análogos & derivados
Di-Hidrotestosterona/metabolismo
[Mh] Termos MeSH secundário: 3-Hidroxiesteroide Desidrogenases/química
3-Hidroxiesteroide Desidrogenases/genética
Androgênios
Ligação Competitiva
Seres Humanos
Modelos Moleculares
Mutagênese Sítio-Dirigida
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 08J2K08A3Y (Dihydrotestosterone); 94ZLA3W45F (Arginine); EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


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[PMID]:28977609
[Au] Autor:Morishita M; Maejima S; Tsukahara S
[Ad] Endereço:Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
[Ti] Título:Gonadal Hormone-Dependent Sexual Differentiation of a Female-Biased Sexually Dimorphic Cell Group in the Principal Nucleus of the Bed Nucleus of the Stria Terminalis in Mice.
[So] Source:Endocrinology;158(10):3512-3525, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We recently reported a female-biased sexually dimorphic area in the mouse brain in the boundary region between the preoptic area and the bed nucleus of the stria terminalis (BNST). We reexamined this area and found that it is a ventral part of the principal nucleus of the BNST (BNSTp). The BNSTp is a male-biased sexually dimorphic nucleus, but the ventral part of the BNSTp (BNSTpv) exhibits female-biased sex differences in volume and neuron number. The volume and neuron number of the BNSTpv were increased in males by neonatal orchiectomy and decreased in females by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. Sex differences in the volume and neuron number of the BNSTpv emerged before puberty. These sex differences became prominent in adulthood with increasing volume in females and loss of neurons in males during the pubertal/adolescent period. Prepubertal orchiectomy did not affect the BNSTpv, although prepubertal ovariectomy reduced the volume increase and induced loss of neurons in the female BNSTpv. In contrast, the volume and neuron number of male-biased sexually dimorphic nuclei that are composed of mainly calbindin neurons and are located in the preoptic area and BNST were decreased by prepubertal orchiectomy but not affected by prepubertal ovariectomy. Testicular testosterone during the postnatal period may defeminize the BNSTpv via binding directly to the androgen receptor and indirectly to the estrogen receptor after aromatization, although defeminization may proceed independently of testicular hormones in the pubertal/adolescent period. Ovarian hormones may act to feminize the BNSTpv during the pubertal/adolescent period.
[Mh] Termos MeSH primário: Neurônios/citologia
Área Pré-Óptica/anatomia & histologia
Núcleos Septais/anatomia & histologia
Diferenciação Sexual
[Mh] Termos MeSH secundário: Androgênios/farmacologia
Animais
Animais Recém-Nascidos
Calbindinas/metabolismo
Contagem de Células
Di-Hidrotestosterona/farmacologia
Estradiol/farmacologia
Estrogênios/farmacologia
Feminino
Imagem Tridimensional
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Masculino
Camundongos
Proteínas do Tecido Nervoso/metabolismo
Neurônios/efeitos dos fármacos
Proteínas Nucleares/metabolismo
Orquiectomia
Tamanho do Órgão
Ovariectomia
Área Pré-Óptica/citologia
Área Pré-Óptica/efeitos dos fármacos
RNA Mensageiro/metabolismo
Núcleos Septais/citologia
Núcleos Septais/efeitos dos fármacos
Testosterona/farmacologia
Quinases Ativadas por p21/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Calbindins); 0 (Estrogens); 0 (Nerve Tissue Proteins); 0 (NeuN protein, mouse); 0 (Nuclear Proteins); 0 (RNA, Messenger); 08J2K08A3Y (Dihydrotestosterone); 3XMK78S47O (Testosterone); 4TI98Z838E (Estradiol); EC 2.7.11.1 (Pak3 protein, mouse); EC 2.7.11.1 (p21-Activated Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00240


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[PMID]:28947209
[Au] Autor:Hata S; Ise K; Azmahani A; Konosu-Fukaya S; McNamara KM; Fujishima F; Shimada K; Mitsuzuka K; Arai Y; Sasano H; Nakamura Y
[Ad] Endereço:Division of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan; Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
[Ti] Título:Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors.
[So] Source:Life Sci;190:15-20, 2017 Dec 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. MAIN METHODS: The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). KEY FINDINGS: DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. SIGNIFICANCE: Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior.
[Mh] Termos MeSH primário: 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética
Carcinoma de Células de Transição/genética
Di-Hidrotestosterona/farmacologia
Proteínas de Membrana/genética
Receptores Androgênicos/genética
Neoplasias da Bexiga Urinária/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Androgênios/farmacologia
Carcinoma de Células de Transição/patologia
Linhagem Celular Tumoral
Movimento Celular/genética
Proliferação Celular/genética
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Masculino
Meia-Idade
Gradação de Tumores
RNA Mensageiro/metabolismo
Neoplasias da Bexiga Urinária/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Membrane Proteins); 0 (RNA, Messenger); 0 (Receptors, Androgen); 08J2K08A3Y (Dihydrotestosterone); EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase); EC 1.3.99.5 (SRD5A1 protein, human); EC 1.3.99.5 (SRD5A2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE


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[PMID]:28938437
[Au] Autor:Shenoy CC; Khan Z; Zheng Y; Jones TL; Khazaie K; Daftary GS
[Ad] Endereço:Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905.
[Ti] Título:Progressive Fibrosis: A Progesterone- and KLF11-Mediated Sexually Dimorphic Female Response.
[So] Source:Endocrinology;158(10):3605-3619, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Progressive scarring is ubiquitous postoperatively and in an array of chronic systemic diseases. Recent studies indicate that such scarring has a high female propensity; females are also almost exclusively affected by endometriosis, a common sex steroid-dependent fibrotic disease. Endometriosis-related fibrosis is regulated epigenetically through transcription factor Krüppel-like factor 11 (KLF11). In response to surgical induction of endometriosis, Klf11-/- female mice develop significant fibrosis in contrast to wild-type mice. We therefore hypothesized that female fibrotic predilection was mediated by differential sex steroid regulation of KLF11/collagen 1a1 signaling and investigated the fibrotic response in wild-type and Klf11-/- male and female animals using a sterile peritonitis model. Fibrosis selectively developed in Klf11-/- females. Fibrosis in these animals was almost completely abrogated by ovariectomy. Ovariectomized animals were selectively supplemented with estradiol, medroxyprogesterone acetate (MPA), or dihydrotestosterone; fibrosis was only observed in mice exposed to MPA. Fibrosis therefore selectively developed in Klf11-/- female mice in response to physiological or pharmacological progesterone. The fibrotic response in these animals was also mitigated in response to antiprogestin therapy. Profibrotic gene expression was activated in a primary human peritoneal cell line in response to KLF11 short hairpin RNA and MPA but not estradiol. KLF11/collagen 1a1 signaling previously shown to be linked to fibrosis was thus selectively dysregulated in MPA-treated cells. Our in vivo and in vitro findings in an animal model and human cells, respectively, suggest that progressive fibrotic scarring is a sexually dimorphic response irrespective of etiology; moreover, it is responsive to novel, individualized therapeutic intervention.
[Mh] Termos MeSH primário: Proteínas de Ligação a DNA/genética
Fibrose/genética
Peritônio/patologia
Progesterona/metabolismo
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Androgênios/farmacologia
Animais
Proteínas de Ciclo Celular/genética
Linhagem Celular
Colágeno Tipo I/metabolismo
Di-Hidrotestosterona/farmacologia
Estradiol/farmacologia
Estrogênios/farmacologia
Feminino
Fibrose/metabolismo
Expressão Gênica
Seres Humanos
Técnicas In Vitro
Masculino
Acetato de Medroxiprogesterona/farmacologia
Camundongos
Camundongos Knockout
Ovariectomia
Peritônio/citologia
Peritônio/efeitos dos fármacos
Peritonite
Progestinas/farmacologia
RNA Interferente Pequeno
Proteínas Repressoras/genética
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Cell Cycle Proteins); 0 (Collagen Type I); 0 (DNA-Binding Proteins); 0 (Estrogens); 0 (KLF11 protein, human); 0 (KLF11 protein, mouse); 0 (Progestins); 0 (RNA, Small Interfering); 0 (Repressor Proteins); 0 (Transcription Factors); 0 (collagen type I, alpha 1 chain); 08J2K08A3Y (Dihydrotestosterone); 4G7DS2Q64Y (Progesterone); 4TI98Z838E (Estradiol); C2QI4IOI2G (Medroxyprogesterone Acetate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00171


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[PMID]:28938398
[Au] Autor:Vanacker C; Moya MR; DeFazio RA; Johnson ML; Moenter SM
[Ad] Endereço:Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109.
[Ti] Título:Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.
[So] Source:Endocrinology;158(10):3553-3564, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation.
[Mh] Termos MeSH primário: Potenciais de Ação/efeitos dos fármacos
Androgênios/farmacologia
Núcleo Arqueado do Hipotálamo/citologia
Di-Hidrotestosterona/farmacologia
Estradiol/farmacologia
Estrogênios/farmacologia
Neurônios/efeitos dos fármacos
Orquiectomia
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Animais
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Encéfalo/fisiologia
Análise por Conglomerados
Dinorfinas/metabolismo
Hormônio Liberador de Gonadotropina/metabolismo
Proteínas de Fluorescência Verde/genética
Kisspeptinas/genética
Kisspeptinas/metabolismo
Masculino
Camundongos
Camundongos Transgênicos
Neurocinina B/metabolismo
Neurônios/metabolismo
Neurônios/fisiologia
Técnicas de Patch-Clamp
Receptores da Neurocinina-3/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Estrogens); 0 (Kiss1 protein, mouse); 0 (Kisspeptins); 0 (Receptors, Neurokinin-3); 08J2K08A3Y (Dihydrotestosterone); 147336-22-9 (Green Fluorescent Proteins); 33515-09-2 (Gonadotropin-Releasing Hormone); 4TI98Z838E (Estradiol); 74913-18-1 (Dynorphins); 86933-75-7 (Neurokinin B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00382


  9 / 8537 MEDLINE  
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[PMID]:28916285
[Au] Autor:Zenata O; Dvorak Z; Vrzal R
[Ad] Endereço:Department of Cell Biology Genetics, Faculty of Science, Palacky University in Olomouc, Slechtitelu 27, Olomouc, CZ-783 71, Czech Republic. Electronic address: zenataOndrej@seznam.cz.
[Ti] Título:Profiling of bisphenol S towards nuclear receptors activities in human reporter cell lines.
[So] Source:Toxicol Lett;281:10-19, 2017 Nov 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bisphenol S (BPS) is heat-stable structural analog of bisphenol A (BPA), a known endocrine disruptor. Due to the effort to replace BPA with BPS, it is essential to know if BPS is suitable non-toxic replacement without reported deleterious effects of BPA. Since most of the BPA effects are ascribed to its ability to activate nuclear receptors, we screened some prominent members of this family in order to confirm or refute some recent findings. We found that BPS insignificantly activated aryl hydrocarbon receptor (AhR) in reporter gene assay and no induction of AhR target gene CYP1A1 was observed in human hepatocytes (HH). BPS was able to act like an antagonist of pregnane X receptor (PXR) in reporter gene assay, but the expression of PXR target gene CYP3A4, was only moderately affected in HH. While BPS antagonized dexamethasone-inducible glucocorticoid receptor (GR)-dependent luciferase activity in reporter gene assay (IC =52µM), it was not able to antagonize dexamethasone effects on GR-target genes, including GILZ, NFKBIA and IL-6. Synergistic effect of BPS (range 0.001-100µM) and DHT (100nM) was observed at androgen receptor (AR) activity level only. In conclusion, we show that BPS had only limited effect on tested nuclear receptors. Moreover, submicromolar concentrations of BPS affected activated AR. Thus, due to the low levels of exposure for humans, BPS is probably of no regulatory concern. However, further investigation should delineate possible impact on male/female development or sexual functions.
[Mh] Termos MeSH primário: Hepatócitos/efeitos dos fármacos
Fenóis/toxicidade
Receptores Citoplasmáticos e Nucleares/metabolismo
Sulfonas/toxicidade
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Citocromo P-450 CYP1A1/genética
Citocromo P-450 CYP1A1/metabolismo
Citocromo P-450 CYP3A/genética
Citocromo P-450 CYP3A/metabolismo
Dexametasona/toxicidade
Di-Hidrotestosterona/toxicidade
Disruptores Endócrinos/toxicidade
Genes Reporter
Células HEK293
Células HeLa
Hepatócitos/metabolismo
Seres Humanos
Interleucina-6/genética
Interleucina-6/metabolismo
Luciferases/genética
Luciferases/metabolismo
Inibidor de NF-kappaB alfa/genética
Inibidor de NF-kappaB alfa/metabolismo
Receptores de Hidrocarboneto Arílico/genética
Receptores de Hidrocarboneto Arílico/metabolismo
Receptores Citoplasmáticos e Nucleares/genética
Receptores de Glucocorticoides/genética
Receptores de Glucocorticoides/metabolismo
Receptores de Esteroides/antagonistas & inibidores
Receptores de Esteroides/genética
Receptores de Esteroides/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endocrine Disruptors); 0 (IL6 protein, human); 0 (Interleukin-6); 0 (NFKBIA protein, human); 0 (Phenols); 0 (Receptors, Aryl Hydrocarbon); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Receptors, Glucocorticoid); 0 (Receptors, Steroid); 0 (Sulfones); 0 (TSC22D3 protein, human); 0 (Transcription Factors); 0 (pregnane X receptor); 08J2K08A3Y (Dihydrotestosterone); 139874-52-5 (NF-KappaB Inhibitor alpha); 7S5I7G3JQL (Dexamethasone); 80-09-1 (bis(4-hydroxyphenyl)sulfone); EC 1.13.12.- (Luciferases); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (CYP1A1 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP1A1); EC 1.14.14.1 (Cytochrome P-450 CYP3A)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170917
[St] Status:MEDLINE


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[PMID]:28905453
[Au] Autor:Neuzillet Y; Raynaud JP; Radulescu C; Fiet J; Giton F; Dreyfus JF; Ghoneim TP; Lebret T; Botto H
[Ad] Endereço:Department of Urology, University of Versailles-Saint-Quentin-en-Yvelines, Foch Hospital, Suresnes, France.
[Ti] Título:Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).
[So] Source:Prostate;77(15):1512-1519, 2017 Nov.
[Is] ISSN:1097-0045
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. METHODS: Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). RESULTS: Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. CONCLUSIONS: STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase.
[Mh] Termos MeSH primário: Hormônios Esteroides Gonadais/sangue
Hormônios Esteroides Gonadais/metabolismo
Próstata/metabolismo
[Mh] Termos MeSH secundário: Idoso
Androstenodiol/sangue
Androstenodiol/metabolismo
Índice de Massa Corporal
Desidroepiandrosterona/sangue
Desidroepiandrosterona/metabolismo
Sulfato de Desidroepiandrosterona/sangue
Sulfato de Desidroepiandrosterona/metabolismo
Di-Hidrotestosterona/sangue
Di-Hidrotestosterona/metabolismo
Estradiol/sangue
Estradiol/metabolismo
Estrona/sangue
Estrona/metabolismo
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Hiperplasia Prostática/sangue
Hiperplasia Prostática/metabolismo
Hiperplasia Prostática/cirurgia
Testosterona/sangue
Testosterona/metabolismo
Neoplasias da Bexiga Urinária/sangue
Neoplasias da Bexiga Urinária/metabolismo
Neoplasias da Bexiga Urinária/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gonadal Steroid Hormones); 08J2K08A3Y (Dihydrotestosterone); 2DI9HA706A (Estrone); 3XMK78S47O (Testosterone); 459AG36T1B (Dehydroepiandrosterone); 4TI98Z838E (Estradiol); 57B09Q7FJR (Dehydroepiandrosterone Sulfate); 95PS51EMXY (Androstenediol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1002/pros.23429



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