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[PMID]:28324066
[Au] Autor:Bailey DJ; Makeyeva YV; Paitel ER; Pedersen AL; Hon AT; Gunderson JA; Saldanha CJ
[Ad] Endereço:Biology, St. Norbert College, De Pere, Wisconsin .
[Ti] Título:Hippocampal Aromatization Modulates Spatial Memory and Characteristics of the Synaptic Membrane in the Male Zebra Finch.
[So] Source:Endocrinology;158(4):852-859, 2017 04 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The estrogen-synthesizing enzyme aromatase is abundant at the synapse in the zebra finch hippocampus (HP), and its inhibition impairs spatial memory function. To more fully test the role of local estradiol (E2) synthesis in memory, the HP of adult male zebra finches was exposed to either control pellets or those containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), ATD and E2, ATD and the G protein-coupled estrogen receptor (GPER) agonist G1, or the antagonist G15 alone. Birds were tested for spatial memory acquisition and performance, and HP levels of the postsynaptic protein PSD95 were measured. ATD-treated birds took longer to reach criterion than control birds, whereas acquisition in ATD+E2 and ATD+G1 birds was indistinguishable from control and ATD treatments. Interestingly, all G15 birds failed to acquire the task. Following a retention interval, ATD birds took the longest to reach the (formerly) baited cup and made the most mistakes. ATD+E2 animals displayed the lowest retention latencies and made fewer mistakes than ATD-treated birds, and ATD+G1 birds did not significantly differ from controls in retention latencies. The amount of PSD95 in the HP was lowest in ATD-treated animals compared with birds with silicone-only-implanted craniotomies, ATD+E2, and ATD+G1 birds, who did not differ in this expression. Thus, spatial memory acquisition and performance appear aromatase and E2 dependent, an effect more reliably revealed after consolidation and/or recall compared to acquisition. E2 may exert this effect via GPERs, resulting in an increase in PSD95 levels that may modify receptor activity or intracellular signaling pathways to increase synaptic strength.
[Mh] Termos MeSH primário: Inibidores da Aromatase/farmacologia
Aromatase/metabolismo
Hipocampo/efeitos dos fármacos
Memória Espacial/efeitos dos fármacos
Membranas Sinápticas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Androstatrienos/farmacologia
Animais
Benzodioxóis/farmacologia
Estradiol/farmacologia
Estrogênios/farmacologia
Tentilhões
Hipocampo/metabolismo
Masculino
Quinolinas/farmacologia
Membranas Sinápticas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline); 0 (Androstatrienes); 0 (Aromatase Inhibitors); 0 (Benzodioxoles); 0 (Estrogens); 0 (Quinolines); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 4TI98Z838E (Estradiol); EC 1.14.14.1 (Aromatase)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1692


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[PMID]:26632865
[Au] Autor:Chan GH; Ho EN; Leung DK; Wong KS; Wan TS
[Ad] Endereço:Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse , Sha Tin, N.T., Hong Kong, China.
[Ti] Título:Targeted Metabolomics Approach To Detect the Misuse of Steroidal Aromatase Inhibitors in Equine Sports by Biomarker Profiling.
[So] Source:Anal Chem;88(1):764-72, 2016 Jan 05.
[Is] ISSN:1520-6882
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The use of anabolic androgenic steroids (AAS) is prohibited in both human and equine sports. The conventional approach in doping control testing for AAS (as well as other prohibited substances) is accomplished by the direct detection of target AAS or their characteristic metabolites in biological samples using hyphenated techniques such as gas chromatography or liquid chromatography coupled with mass spectrometry. Such an approach, however, falls short when dealing with unknown designer steroids where reference materials and their pharmacokinetics are not available. In addition, AASs with fast elimination times render the direct detection approach ineffective as the detection window is short. A targeted metabolomics approach is a plausible alternative to the conventional direct detection approach for controlling the misuse of AAS in sports. Because the administration of AAS of the same class may trigger similar physiological responses or effects in the body, it may be possible to detect such administrations by monitoring changes in the endogenous steroidal expression profile. This study attempts to evaluate the viability of using the targeted metabolomics approach to detect the administration of steroidal aromatase inhibitors, namely androst-4-ene-3,6,17-trione (6-OXO) and androsta-1,4,6-triene-3,17-dione (ATD), in horses. Total (free and conjugated) urinary concentrations of 31 endogenous steroids were determined by gas chromatography-tandem mass spectrometry for a group of 2 resting and 2 in-training thoroughbred geldings treated with either 6-OXO or ATD. Similar data were also obtained from a control (untreated) group of in-training thoroughbred geldings (n = 28). Statistical processing and chemometric procedures using principle component analysis and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) have highlighted 7 potential biomarkers that could be used to differentiate urine samples obtained from the control and the treated groups. On the basis of this targeted metabolomic approach, the administration of 6-OXO and ATD could be detected for much longer relative to that of the conventional direct detection approach.
[Mh] Termos MeSH primário: Androstatrienos/urina
Androstenos/urina
Inibidores da Aromatase/urina
Doping nos Esportes
Cavalos/urina
Metabolômica/métodos
Esteroides/urina
[Mh] Termos MeSH secundário: Androstatrienos/química
Androstatrienos/metabolismo
Androstenos/química
Androstenos/metabolismo
Animais
Aromatase/metabolismo
Inibidores da Aromatase/química
Inibidores da Aromatase/metabolismo
Biomarcadores/metabolismo
Biomarcadores/urina
Cromatografia Gasosa
Doping nos Esportes/prevenção & controle
Hidrólise
Masculino
Estrutura Molecular
Esportes
Esteroides/química
Esteroides/metabolismo
Detecção do Abuso de Substâncias
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstatrienes); 0 (Androstenes); 0 (Aromatase Inhibitors); 0 (Biomarkers); 0 (Steroids); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); EC 1.14.14.1 (Aromatase); L8L0381OBP (androst-4-ene-3,6,17-trione)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151204
[St] Status:MEDLINE
[do] DOI:10.1021/acs.analchem.5b03165


  3 / 165 MEDLINE  
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[PMID]:26346733
[Au] Autor:Small TW; Brenowitz EA; Wojtenek W; Moore IT
[Ad] Endereço:Department of Biological Sciences, Virginia Tech, Blacksburg, Va., USA.
[Ti] Título:Testosterone Mediates Seasonal Growth of the Song Control Nuclei in a Tropical Bird.
[So] Source:Brain Behav Evol;86(2):110-21, 2015.
[Is] ISSN:1421-9743
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:In mid- to high-latitude songbirds, seasonal reproduction is stimulated by increasing day length accompanied by elevated plasma sex steroid levels, increased singing, and growth of the song control nuclei (SCN). Plasticity of the SCN and song behavior are primarily mediated by testosterone (T) and its metabolites in most species studied thus far. However, the majority of bird species are tropical and have less pronounced seasonal reproductive cycles. We have previously documented that equatorial rufous-collared sparrows (Zonotrichia capensis) exhibit seasonal neuroplasticity in the SCN. Manipulating T in these birds, however, did not alter singing behavior. In the current study, we investigated whether T mediates plasticity of the SCN in a similar manner to temperate songbirds. In the first experiment, we treated captive male birds with T or blank implants during the nonbreeding season. In a second experiment, we treated captive male birds with either blank implants, T-filled implants, T with flutamide (FLU; an androgen receptor antagonist) or T with FLU and 1,4,6-androstatriene-3,17-dione (ATD; an estrogen synthesis inhibitor) during the breeding season. In both experiments, the volumes of the brain areas high vocal center (HVC), Area X, and robust nucleus of the arcopallium (RA) were measured along with singing behavior. In summary, T stimulated growth of HVC and RA, and the combined effect of FLU and ATD reversed this effect in HVC. Area X was not affected by T treatment in either experiment. Neither T-treated birds nor controls sang in captivity during either experiment. Together, these data indicate that T mediates seasonal changes in the HVC and RA of both tropical and higher- latitude bird species even if the environmental signals differ. However, unlike most higher-latitude songbirds, we found no evidence that motivation to sing or growth of Area X are stimulated by T under captive conditions.
[Mh] Termos MeSH primário: Centro Vocal Superior/efeitos dos fármacos
Neurônios/fisiologia
Estações do Ano
Testosterona/farmacologia
Clima Tropical
Vocalização Animal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Análise de Variância
Antagonistas de Androgênios/farmacologia
Androstatrienos/farmacologia
Animais
Contagem de Células
Inibidores Enzimáticos/farmacologia
Flutamida/farmacologia
Centro Vocal Superior/citologia
Masculino
Plasticidade Neuronal/efeitos dos fármacos
Radioimunoensaio
Aves Canoras
Testosterona/sangue
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Androgen Antagonists); 0 (Androstatrienes); 0 (Enzyme Inhibitors); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 3XMK78S47O (Testosterone); 76W6J0943E (Flutamide)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150909
[St] Status:MEDLINE
[do] DOI:10.1159/000437412


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[PMID]:26232614
[Au] Autor:Yahr P
[Ad] Endereço:Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, United States. Electronic address: piyahr@uci.edu.
[Ti] Título:Two aromatase inhibitors inhibit the ability of a third to promote mating in male rats.
[So] Source:Horm Behav;75:41-4, 2015 Sep.
[Is] ISSN:1095-6867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aromatase, the enzyme that aromatizes androstenedione (A) to estrone and testosterone (T) to estradiol (E), affects androgen control of male sex behavior in many vertebrates. In male monkeys, rats and quail, E mimics the ability of T to promote mating, and aromatase inhibitors block mating induced by T but not E. Aromatase inhibitors include androgens with different A-rings than T and A, e.g., 1,4,6-androstatriene-3,17-dione (ATD), azoles, e.g., fadrozole, and androgens α-halogenated at carbon 6, e.g., 6α-bromoA, 6α-fluoroA and 6α-fluoroT. 6α-FluoroT is the only 6α-halogenated androgen studied in regard to mating. It promotes mating in male rats and quail and was studied, before it was known to inhibit aromatase, because it cannot be aromatized yet has the same A-ring as T. 6α-FluoroT might promote mating by binding estrogen receptors (ER) directly, i.e., unassisted, or by metabolism to an androgen that binds ER. Since neither process would require aromatase, this study tested both hypotheses by determining how mating induced in castrated male rats by 6α-fluoroT is affected by ATD and fadrozole. Both aromatase inhibitors inhibited the effects of 6α-fluoroT on mating. Thus, 6α-fluoroT does not promote mating by direct ER binding or metabolism to another androgen. Since aromatase underlies a process in which 6α-fluoroT, unlike most nonaromatizable androgens, mimics T effects on male sex behavior, the process must involve a feature that 6α-fluoroT shares with T but not other nonaromatizable androgens. A-ring structure is a candidate. A hypothesis is also offered for how aromatase may participate without aromatizing the androgen.
[Mh] Termos MeSH primário: Androstatrienos/farmacologia
Inibidores da Aromatase/farmacologia
Fadrozol/farmacologia
Comportamento Sexual Animal/efeitos dos fármacos
Testosterona/análogos & derivados
[Mh] Termos MeSH secundário: Androgênios/farmacologia
Androstenodiona/farmacologia
Animais
Interações Medicamentosas
Estradiol/farmacologia
Estrona/farmacologia
Feminino
Masculino
Ratos
Ratos Long-Evans
Ratos Sprague-Dawley
Reprodução/efeitos dos fármacos
Testosterona/antagonistas & inibidores
Testosterona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (6-fluorotestosterone); 0 (Androgens); 0 (Androstatrienes); 0 (Aromatase Inhibitors); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 2DI9HA706A (Estrone); 3XMK78S47O (Testosterone); 409J2J96VR (Androstenedione); 4TI98Z838E (Estradiol); H3988M64PU (Fadrozole)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161203
[Lr] Data última revisão:
161203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150802
[St] Status:MEDLINE


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[PMID]:26086546
[Au] Autor:Bethea CL; Phu K; Kim A; Reddy AP
[Ad] Endereço:Division of Reproductive and Development Science, Oregon National Primate Research Center, Beaverton, OR 97006, United States; Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, United States; Department of Obstetrics and Gynecology, Oregon Health and Science Uni
[Ti] Título:Androgen metabolites impact CSF amines and axonal serotonin via MAO-A and -B in male macaques.
[So] Source:Neuroscience;301:576-89, 2015 Aug 20.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A number of studies have shown that mutations or deletions of the monoamine oxidase-A (MAO-A) gene cause elevated CNS serotonin and elevated impulsive aggression in humans and animal models. In addition, low cerebrospinal fluid (CSF) 5-hydroxyindole acetic acid (5HIAA) has been documented in a limited number of violent criminal populations and in macaques that exhibit impulsive aggression. To reconcile these different analyses, we hypothesized that CSF 5HIAA reflected degradation of serotonin by the activity of MAO-A; and that low MAO-A activity would result in lower CSF 5HIAA, but overall higher serotonin in the CNS. To test this hypothesis, male Japanese macaques (Macaca fuscata) were castrated, rested for 5-7months, and then treated for 3months with [1] placebo, [2] testosterone (T), [3] dihydrotestosterone (DHT; non-aromatizable androgen) and 1,4,6-androstatriene-3,17-dione (ATD) (steroidal aromatase inhibitor), or [4] flutamide (FLUT; androgen antagonist) and ATD (n=5/group). These treatments enable isolation of androgen and estrogen activities. In the dorsal raphe, MAO-A and MAO-B expressions were determined with in situ hybridization (ISH) and protein expression of aromatase was determined with immunohistochemistry (IHC). CSF concentrations of 5HIAA, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were determined with liquid chromatography/mass spectrometry (LC/MS). From the same animals, previously published data on serotonin axon density were used as a proxy for CNS serotonin. Aromatase conversion of T to estrogen (E) suppressed MAO-A (positive pixel area, p=0.0045), but androgens increased MAO-B (positive pixel area, p=0.014). CSF 5HIAA was suppressed by conversion of T to E (Cohen's d=0.6). CSF 5HIAA was positively correlated with MAO-A-positive pixel area (r(2)=0.78). CSF 5HIAA was inversely correlated with serotonin axon-positive pixel area (r(2)=0.69). In summary, CSF 5HIAA reflects MAO-A activity rather than global serotonin. Low CSF 5HIAA may, in this paradigm, reflect higher serotonin activity. Androgens lower MAO-A activity via metabolism to E, thus elevating CNS serotonin and decreasing CSF 5HIAA. Since androgens increase certain types of aggression, these data are consistent with studies demonstrating that lower MAO-A activity is associated with elevated serotonin and increased aggression.
[Mh] Termos MeSH primário: Aminas/líquido cefalorraquidiano
Androgênios/metabolismo
Axônios/metabolismo
Monoaminoxidase/metabolismo
Serotonina/metabolismo
[Mh] Termos MeSH secundário: Análise de Variância
Antagonistas de Androgênios/farmacologia
Androgênios/farmacologia
Androstatrienos/farmacologia
Animais
Aromatase/metabolismo
Inibidores da Aromatase/farmacologia
Di-Hidrotestosterona/farmacologia
Flutamida/farmacologia
Macaca fascicularis
Masculino
Monoaminoxidase/genética
RNA Mensageiro/metabolismo
Núcleos da Rafe/metabolismo
Testosterona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (1,4,6-androstatrien-3,17-dione); 0 (Amines); 0 (Androgen Antagonists); 0 (Androgens); 0 (Androstatrienes); 0 (Aromatase Inhibitors); 0 (RNA, Messenger); 08J2K08A3Y (Dihydrotestosterone); 333DO1RDJY (Serotonin); 3XMK78S47O (Testosterone); 76W6J0943E (Flutamide); EC 1.14.14.1 (Aromatase); EC 1.4.3.4 (Monoamine Oxidase)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150619
[St] Status:MEDLINE


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[PMID]:26031748
[Au] Autor:Kwok WH; Leung GN; Wan TS; Curl P; Schiff PJ
[Ad] Endereço:Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong, China. Electronic address: wh.kwok@hkjc.org.hk.
[Ti] Título:Metabolic study of androsta-1,4,6-triene-3,17-dione in horses using liquid chromatography/high resolution mass spectrometry.
[So] Source:J Steroid Biochem Mol Biol;152:142-54, 2015 Aug.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Androsta-1,4,6-triene-3,17-dione (ATD) is an irreversible steroidal aromatase inhibitor and is marketed as a supplement. It has been reported to effectively reduce estrogen biosynthesis and significantly increase the levels of endogenous steroids such as dihydrotestosterone and testosterone in human. ATD abuses have been reported in human sports. Its metabolism in human has been studied, and the in vitro metabolic study of ATD in horses has been reported, however, little is known about its biotransformation and elimination in horses. This paper describes the in vitro and in vivo metabolism studies of ATD in horses, with an objective of identifying the target metabolites with the longest detection time for controlling ATD abuse. In vitro metabolism studies of ATD were performed using homogenized horse liver. ATD was found to be extensively metabolized, and its metabolites could not be easily characterized by gas chromatography/mass spectrometry (GC/MS) due to insufficient sensitivity. Liquid chromatography/high resolution mass spectrometry (LC/HRMS) was therefore employed for the identification of in vitro metabolites. The major biotransformations observed were combinations of reduction of the olefin groups and/or the keto group at either C3 or C17 position. In addition, mono-hydroxylation in the D-ring was observed along with reduction of the olefin groups and/or the keto group at C17 position. Fourteen in vitro metabolites, including two epimers of androsta-1,4,6-trien-17-ol-3-one (M1a, M1b), androsta-4,6-diene-3,17-dione (M2), boldione (M3), androsta-4,6-diene-17ß-ol-3-one (M4), androsta-4,6-diene-3-ol-17-one (M5), boldenone and epi-boldenone (M6a, M6b), four stereoisomers of hydroxylated androsta-1,4,6-trien-17-ol-3-one (M7a to M7d), and two epimers of androsta-1,4-diene-16α,17-diol (M8a, M8b), were identified. The identities of all metabolites, except M1a, M5, M7a to M7d, were confirmed by matching with authentic reference standards using LC/HRMS. For the in vivo metabolism studies, two thoroughbred geldings were each administered with 800 mg of ATD by stomach tubing. ATD, and twelve out of the fourteen in vitro metabolites, including M1a, M1b, M2, M4, M5, M6, M7a to M7d, M8a and M8b, were detected in post-administration urine. Two additional urinary metabolites, namely stereoisomers of hydroxylated androsta-4,6-dien-17-ol-3-one (M9a, M9b), were tentatively identified by mass spectral interpretation. Elevated level of testosterone was also observed. In post-administration blood samples, only the parent drug, M1b and M2 were identified. This study showed that the detection of ATD administration would be best achieved by either monitoring the metabolites M1b (androsta-1,4,6-trien-17ß-ol-3-one) or M4 (both excreted as sulfate conjugates) in urine, which could be detected for up to a maximum of 77 h post-administration. The analyte of choice for plasma is M1b, which could be detected for up to 28 h post administration.
[Mh] Termos MeSH primário: Androstatrienos/metabolismo
Cavalos/metabolismo
Substâncias para Melhoria do Desempenho/metabolismo
Testosterona/urina
[Mh] Termos MeSH secundário: Alcenos/metabolismo
Androstadienos
Animais
Cromatografia Líquida/veterinária
Doping nos Esportes
Fígado/metabolismo
Espectrometria de Massas/veterinária
Metaboloma
Detecção do Abuso de Substâncias/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkenes); 0 (Androstadienes); 0 (Androstatrienes); 0 (Performance-Enhancing Substances); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 3XMK78S47O (Testosterone)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150603
[St] Status:MEDLINE


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[PMID]:22120997
[Au] Autor:a Marca Pereira ML; Eppler E; Thorpe KL; Wheeler JR; Burkhardt-Holm P
[Ad] Endereço:Programm MGU Mensch-Gesellschaft-Umwelt, Department of Environmental Sciences, University of Basel, Vesalgasse 1, Basel 4051, Switzerland.
[Ti] Título:Molecular and cellular effects of chemicals disrupting steroidogenesis during early ovarian development of brown trout (Salmo trutta fario).
[So] Source:Environ Toxicol;29(2):199-206, 2014 Feb.
[Is] ISSN:1522-7278
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A range of chemicals found in the aquatic environment have the potential to influence endocrine function and affect sexual development by mimicking or antagonizing the effects of hormones, or by altering the synthesis and metabolism of hormones. The aim of this study was to evaluate whether the effects of chemicals interfering with sex hormone synthesis may affect the regulation of early ovarian development via the modulation of sex steroid and insulin-like growth factor (IGF) systems. To this end, ex vivo ovary cultures of juvenile brown trout (Salmo trutta fario) were exposed for 2 days to either 1,4,6-androstatriene-3,17-dione (ATD, a specific aromatase inhibitor), prochloraz (an imidazole fungicide), or tributyltin (TBT, a persistent organic pollutant). Further, juvenile female brown trout were exposed in vivo for 2 days to prochloraz or TBT. The ex vivo and in vivo ovarian gene expression of the aromatase (CYP19), responsible for estrogen production, and of IGF1 and 2 were compared. Moreover, 17ß-estradiol (E2) and testosterone (T) production from ex vivo ovary cultures was assessed. Ex vivo exposure to ATD inhibited ovarian E2 synthesis, while T levels accumulated. However, ATD did not affect ex vivo expression of cyp19, igf1, or igf2. Ex vivo exposure to prochloraz inhibited ovarian E2 production, but did not affect T levels. Further prochloraz up-regulated igf1 expression in both ex vivo and in vivo exposures. TBT exposure did not modify ex vivo synthesis of either E2 or T. However, in vivo exposure to TBT down-regulated igf2 expression. The results indicate that ovarian inhibition of E2 production in juvenile brown trout might not directly affect cyp19 and igf gene expression. Thus, we suggest that the test chemicals may interfere with both sex steroid and IGF systems in an independent manner, and based on published literature, potentially lead to endocrine dysfunction and altered sexual development.
[Mh] Termos MeSH primário: Disruptores Endócrinos/toxicidade
Ovário/efeitos dos fármacos
Truta
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Androstatrienos/toxicidade
Animais
Aromatase/genética
Inibidores da Aromatase/toxicidade
Estradiol/metabolismo
Feminino
Fungicidas Industriais/toxicidade
Expressão Gênica/efeitos dos fármacos
Imidazóis/toxicidade
Fator de Crescimento Insulin-Like I/genética
Fator de Crescimento Insulin-Like II/genética
Ovário/metabolismo
Testosterona/metabolismo
Compostos de Trialquitina/toxicidade
Truta/genética
Truta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androstatrienes); 0 (Aromatase Inhibitors); 0 (Endocrine Disruptors); 0 (Fungicides, Industrial); 0 (Imidazoles); 0 (Trialkyltin Compounds); 0 (Water Pollutants, Chemical); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 3XMK78S47O (Testosterone); 4TI98Z838E (Estradiol); 4XDX163P3D (tributyltin); 67763-96-6 (Insulin-Like Growth Factor I); 67763-97-7 (Insulin-Like Growth Factor II); 99SFL01YCL (prochloraz); EC 1.14.14.1 (Aromatase)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111129
[St] Status:MEDLINE
[do] DOI:10.1002/tox.20786


  8 / 165 MEDLINE  
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[PMID]:22315450
[Au] Autor:Bingham B; Wang NX; Innala L; Viau V
[Ad] Endereço:Department of Cellular and Physiological Sciences, Life Sciences Centre, The University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.
[Ti] Título:Postnatal aromatase blockade increases c-fos mRNA responses to acute restraint stress in adult male rats.
[So] Source:Endocrinology;153(4):1603-8, 2012 Apr.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent evidence suggests that the aromatization of testosterone to estrogen is important for the organizing effects of neonatal testosterone on neuroendocrine responses to acute challenges. However, the extent to which neonatal inhibition of aromatase alters the stress-induced activation of neural pathways has not been examined. Here we assessed central patterns of c-fos mRNA induced by 30 min of restraint in 65-d-old adult male rats that were implanted with sc capsules of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), introduced within 12 h of birth and removed on d 21 of weaning. Neonatal ATD decreased the expression of arginine vasopressin within extrahypothalamic regions in adults, confirming reduced estrogen exposure during development. As adults, ATD-treated animals showed higher corticosterone responses at 30 min of restraint exposure compared with control animals as well as higher c-fos expression levels in the paraventricular nucleus of the hypothalamus. ATD treatment also increased stress-induced c-fos within several limbic regions of the forebrain, in addition to areas involved in somatosensory processing. Based on these results, we propose that the conversion of testosterone to estrogen during the neonatal period exerts marked, system-wide effects to organize adult neuroendocrine responses to homeostatic threat.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Animais Recém-Nascidos/metabolismo
Aromatase/deficiência
Proteínas Proto-Oncogênicas c-fos/metabolismo
RNA Mensageiro/metabolismo
Restrição Física/fisiologia
Estresse Fisiológico/fisiologia
[Mh] Termos MeSH secundário: Androstatrienos/farmacologia
Animais
Aromatase/efeitos dos fármacos
Inibidores da Aromatase/farmacologia
Estrogênios/metabolismo
Masculino
Modelos Animais
Núcleo Hipotalâmico Paraventricular/metabolismo
Prosencéfalo/metabolismo
Ratos
Ratos Sprague-Dawley
Testosterona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Androstatrienes); 0 (Aromatase Inhibitors); 0 (Estrogens); 0 (Proto-Oncogene Proteins c-fos); 0 (RNA, Messenger); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 3XMK78S47O (Testosterone); EC 1.14.14.1 (Aromatase)
[Em] Mês de entrada:1207
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:120209
[St] Status:MEDLINE
[do] DOI:10.1210/en.2011-1749


  9 / 165 MEDLINE  
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[PMID]:21377487
[Au] Autor:Henley CL; Nunez AA; Clemens LG
[Ad] Endereço:Departments of Zoology and Psychology, and the Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
[Ti] Título:Hormones of choice: the neuroendocrinology of partner preference in animals.
[So] Source:Front Neuroendocrinol;32(2):146-54, 2011 Apr.
[Is] ISSN:1095-6808
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Partner preference behavior can be viewed as the outcome of a set of hierarchical choices made by an individual in anticipation of mating. The first choice involves approaching a conspecific verses an individual of another species. As a rule, a conspecific is picked as a mating partner, but early life experiences can alter that outcome. Within a species, an animal then has the choice between a member of the same sex or the opposite sex. The final choice is for a specific individual. This review will focus on the middle choice, the decision to mate with either a male or a female. Available data from rats, mice, and ferrets point to the importance of perinatal exposure to steroid hormones in the development of partner preferences, as well as the importance of activational effects in adulthood. However, the particular effects of this hormone exposure show species differences in both the specific steroid hormone responsible for the organization of behavior and the developmental period when it has its effect. Where these hormones have an effect in the brain is mostly unknown, but regions involved in olfaction and sexual behavior, as well as sexually dimorphic regions, seem to play a role. One limitation of the literature base is that many mate or 'partner preference studies' rely on preference for a specific stimulus (usually olfaction) but do not include an analysis of the relation, if any, that stimulus has to the choice of a particular sexual partner. A second limitation has been the almost total lack of attention to the type of behavior that is shown by the choosing animal once a 'partner' has been chosen, specifically, if the individual plays a mating role typical of its own sex or the opposite sex. Additional paradigms that address these questions are needed for better understanding of partner preferences in rodents.
[Mh] Termos MeSH primário: Comportamento de Escolha/fisiologia
Preferência de Acasalamento Animal
[Mh] Termos MeSH secundário: Androstatrienos/farmacologia
Animais
Castração
Comportamento de Escolha/efeitos dos fármacos
Feminino
Furões
Hormônios
Masculino
Camundongos
Nitromifeno/farmacologia
Ligação do Par
Gravidez
Efeitos Tardios da Exposição Pré-Natal
Área Pré-Óptica/efeitos dos fármacos
Área Pré-Óptica/fisiologia
Ratos
Caracteres Sexuais
Olfato
Testosterona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (1,4,6-androstatrien-3,17-dione); 0 (Androstatrienes); 0 (Hormones); 3XMK78S47O (Testosterone); 5FS1NJ6Q8N (Nitromifene)
[Em] Mês de entrada:1108
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110308
[St] Status:MEDLINE
[do] DOI:10.1016/j.yfrne.2011.02.010


  10 / 165 MEDLINE  
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[PMID]:21276476
[Au] Autor:a Marca Pereira ML; Wheeler JR; Thorpe KL; Burkhardt-Holm P
[Ad] Endereço:Programm MGU Mensch-Gesellschaft-Umwelt, Department of Environmental Sciences, University of Basel, Vesalgasse 1, Basel, Switzerland. maria.amarca@unibas.ch
[Ti] Título:Development of an ex vivo brown trout (Salmo trutta fario) gonad culture for assessing chemical effects on steroidogenesis.
[So] Source:Aquat Toxicol;101(3-4):500-11, 2011 Feb.
[Is] ISSN:1879-1514
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A variety of natural and synthetic environmental substances have been shown to disrupt vertebrate reproduction through mimicking or modifying the regulation of the endocrine system. Tests to screen for any such chemicals that directly interact with the steroid hormone receptors are widely available; however, few tests have been developed to identify chemicals that affect endocrine function through non-receptor mediated mechanisms. The aim of this study was, therefore, to develop an assay for the identification of substances that disrupt the activity of enzymes involved in the sex steroid biosynthesis cascade, in particular the aromatase enzyme, CYP19, that catalyses the final conversion of androgens to estrogens. A gonad ex vivo assay was developed using gonad explants harvested from juvenile brown trout and cultured in a modified Leibovitz medium. Effects on sex steroid biosynthesis were quantified through measurement of 17ß-estradiol (E2) and testosterone (T) concentrations in the medium after 2 days incubation. Exposure of ovary explants to 100 ng/mL 1,4,6-androstatriene-3,17-dione (ATD), a potent pharmaceutical aromatase inhibitor, reduced E2 concentrations and elevated T concentrations confirming that CYP19 activity could be inhibited in the assay. Exposure of ovary explants to 250 ng/mL prochloraz, an imidazole fungicide, also reduced E2 concentrations but did not affect T levels, consistent with reports that in addition to inhibiting CYP19 activity, prochloraz also inhibits enzymes in the steroidogenic pathway upstream of the CYP19 enzyme. Exposure to a third chemical, tributyltin (TBT), did not affect T or E2 concentrations, further supporting previous evidence that the CYP19 modulating effects of this chemical are not mediated through direct inhibition of CYP19 activity. These results demonstrate that the gonad ex vivo assay developed here can be successfully used to identify substances that disrupt sex steroid biosynthesis and further that it has the potential to inform on their specific mode of action.
[Mh] Termos MeSH primário: Aromatase/metabolismo
Técnicas de Cultura de Células/métodos
Hormônios Esteroides Gonadais/biossíntese
Gônadas/citologia
Truta
[Mh] Termos MeSH secundário: Androstatrienos/farmacologia
Animais
Inibidores da Aromatase/farmacologia
Estradiol/metabolismo
Feminino
Fungicidas Industriais/toxicidade
Gônadas/metabolismo
Imidazóis/toxicidade
Masculino
Testosterona/metabolismo
Compostos de Trialquitina/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Androstatrienes); 0 (Aromatase Inhibitors); 0 (Fungicides, Industrial); 0 (Gonadal Steroid Hormones); 0 (Imidazoles); 0 (Trialkyltin Compounds); 217A6T1V8N (androsta-1,4,6-triene-3,17-dione); 3XMK78S47O (Testosterone); 4TI98Z838E (Estradiol); 4XDX163P3D (tributyltin); 99SFL01YCL (prochloraz); EC 1.14.14.1 (Aromatase)
[Em] Mês de entrada:1105
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110201
[St] Status:MEDLINE
[do] DOI:10.1016/j.aquatox.2010.12.008



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