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[Au] Autor:Marti N; Bouchoucha N; Sauter KS; Flück CE
[Ad] Endereço:Division of Pediatric Endocrinology, Department of Pediatrics and Department of Clinical Research, University of Bern, Bern, Switzerland.
[Ti] Título:Resveratrol inhibits androgen production of human adrenocortical H295R cells by lowering CYP17 and CYP21 expression and activities.
[So] Source:PLoS One;12(3):e0174224, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive effects on the human metabolism as caloric restriction. Recently, positive effects of resveratrol on steroid biosynthesis in cell systems and in humans suffering from polycystic ovary syndrome have also been reported, but the exact mechanism of this action remains unknown. Sirtuins seem targeted by resveratrol to mediate its action on energy homeostasis. In this study, we investigated the mechanisms of action of resveratrol on steroidogenesis in human adrenal H295R cells. Resveratrol was found to inhibit protein expression and enzyme activities of CYP17 and CYP21. It did not alter CYP17 and CYP21 mRNA expression, nor protein degradation. Only SIRT3 mRNA expression was found to be altered by resveratrol, but SIRT1, 3 and 5 overexpression did not result in a change in the steroid profile of H295R cells, indicating that resveratrol may not engage sirtuins to modulate steroid production. Previous studies showed that starvation leads to a hyperandrogenic steroid profile in H295R cells through inhibition of PKB/Akt signaling, and that resveratrol inhibits steroidogenesis of rat ovarian theca cells via the PKB/Akt pathway. Therefore, the effect of resveratrol on PKB/Akt signaling was tested in H295R cells and was found to be decreased under starvation growth conditions, but not under normal growth conditions. Overall, these properties of action together with recent clinical findings make resveratrol a candidate for the treatment of hyperandrogenic disorders such as PCOS.
[Mh] Termos MeSH primário: Androgênios/biossíntese
Anti-Inflamatórios não Esteroides/farmacologia
Família 21 do Citocromo P450/antagonistas & inibidores
Biossíntese de Proteínas/efeitos dos fármacos
Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Córtex Suprarrenal/citologia
Córtex Suprarrenal/metabolismo
Linhagem Celular
Família 21 do Citocromo P450/biossíntese
Família 21 do Citocromo P450/metabolismo
Seres Humanos
Proteínas Proto-Oncogênicas c-akt/metabolismo
RNA Mensageiro/biossíntese
Sirtuína 3/biossíntese
Sirtuína 3/genética
Esteroide 17-alfa-Hidroxilase/biossíntese
Esteroide 17-alfa-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Androgens); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (RNA, Messenger); 0 (Stilbenes); EC (Cytochrome P450 Family 21); EC (Steroid 17-alpha-Hydroxylase); EC (Proto-Oncogene Proteins c-akt); EC 3.5.1.- (SIRT3 protein, human); EC 3.5.1.- (Sirtuin 3); Q369O8926L (resveratrol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174224

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[Au] Autor:Robic A; Feve K; Louveau I; Riquet J; Prunier A
[Ad] Endereço:INRA, UMR1388-GenPhySE, Castanet Tolosan, France.
[Ti] Título:Exploration of steroidogenesis-related genes in testes, ovaries, adrenals, liver and adipose tissue in pigs.
[So] Source:Anim Sci J;87(8):1041-7, 2016 Aug.
[Is] ISSN:1740-0929
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:To explore the metabolism of steroids in the pig species, a qualitative PCR analysis was performed for the main transcript of 27 genes involved in steroid metabolism. We compared samples of testes, adipose tissue and liver from immature and peripubertal males, adrenal cortex from peripubertal males, ovaries from cyclic females and adipose tissue from peripubertal females. Some genes were shown to have a tissue-specific expression. Two of them were expressed only in testes, ovaries and adrenals: CYP11A1 and CYP11B. The CYP21 and HSD17B3 genes, were expressed respectively only in adrenals and only in testes. Very few differences were observed between transcriptional patterns of peripubertal testes and adrenal glands as well as between male and female fat tissues. However, the expression of genes involved in the sulfonation of steroids was higher in testes than in adrenals from males. Main differences between ovaries and testes were observed for HSD17B1/2/3, AKR1C-pig6 and sulfotransferase genes (SULT2A1/SULT2B1). The present study shows that the SRD5A2 and CYP21 genes were not involved in the testicular biosynthesis of androstenone. It also shows that porcine adrenal glands produce essentially corticosteroids and that fat tissue is unable to produce de novo steroids.
[Mh] Termos MeSH primário: Tecido Adiposo/metabolismo
Glândulas Suprarrenais/metabolismo
Regulação Enzimológica da Expressão Gênica
Expressão Gênica
[Mh] Termos MeSH secundário: 17-Hidroxiesteroide Desidrogenases/genética
17-Hidroxiesteroide Desidrogenases/metabolismo
20-Hidroxiesteroide Desidrogenases/genética
20-Hidroxiesteroide Desidrogenases/metabolismo
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética
Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo
Família 21 do Citocromo P450/genética
Família 21 do Citocromo P450/metabolismo
Especificidade de Órgãos/genética
Esteroide 11-beta-Hidroxilase/genética
Esteroide 11-beta-Hidroxilase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroids); EC 1.1.- (17-Hydroxysteroid Dehydrogenases); EC 1.1.1.- (20-Hydroxysteroid Dehydrogenases); EC 1.1.1.- (3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase); EC (Cytochrome P450 Family 21); EC (Steroid 11-beta-Hydroxylase); EC (Cholesterol Side-Chain Cleavage Enzyme); EC 2.8.2.- (Sulfotransferases); EC (alcohol sulfotransferase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170316
[Lr] Data última revisão:
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160721
[St] Status:MEDLINE
[do] DOI:10.1111/asj.12532

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