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1.
Arch Pharm (Weinheim) ; 347(5): 320-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24497156

RESUMO

Flank organs are an androgen-dependent pilosebaceous complex present in male and female hamsters. These organs have been used for the evaluation of antiandrogenic drugs, which could be used for the treatment of androgen-dependent afflictions. This study demonstrated the role of four different steroidal carbamates 7-10 in the expression of mRNAs coding for different enzymes involved in the lipid metabolism in flank organs. To determine the biological effects of compounds 7-10 on the expression of mRNA coding for lipid enzymes, steroids 7-10, testosterone (T), progesterone (P), and/or 7-10 were applied on the flank organs. Later, the mRNA expression for the enzymes was determined by polymerase chain reaction. The binding of 8 and 9 to the progesterone receptor (PR) as well as their effects on the activity of 5α-reductase were also evaluated. Treatments with T, P, and 7-10 increased the mRNA expression for glycerol 3-phosphate acyl transferase (GPAT), ß-hydroxy-ß-methylglutaryl-CoA synthase (HMG-CoA-S), ß-hydroxy-ß-methylglutaryl-CoA reductase (HMG-CoA-R), phosphatidylinositol synthase (PI-S), and squalene-synthase (SQ-S). However, the combined treatments with P + 7-10 decreased the expression of GPAT, HMG-CoA-S, and HMG-CoA-R. Expression of mRNA for all enzymes was variable under treatment with T + 7-10. Data showed that these carbamates did not bind to the PR, but inhibited the activity of 5α-reductase. Carbamates 7-10 changed the mRNA expression model induced by T and P in flank organs.


Assuntos
Carbamatos/farmacologia , RNA Mensageiro/genética , Glândulas Sebáceas/efeitos dos fármacos , Glândulas Sebáceas/enzimologia , Esteroides/farmacologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Animais , Ligação Competitiva , CDP-Diacilglicerol-Inositol 3-Fosfatidiltransferase/genética , Carbamatos/química , Cricetinae , Farnesil-Difosfato Farnesiltransferase/genética , Feminino , Glicerol-3-Fosfato O-Aciltransferase/genética , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Masculino , Mesocricetus , Estrutura Molecular , Ovariectomia , Próstata/efeitos dos fármacos , Próstata/enzimologia , RNA Mensageiro/metabolismo , Coelhos , Receptores de Progesterona/metabolismo , Pele/efeitos dos fármacos , Pele/enzimologia , Esteroides/química
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