RESUMEN
Coexistence of hyperinsulinemia and hyperandrogenism in women has been frequently described. Most of the studies addressing this issue have focused on the mechanisms by which insulin produces hyperandrogenism. In the present study, we analyzed the effects of testosterone in vivo and in vitro upon insulin gene expression and release in the rat. Our studies demonstrate that testosterone increases insulin messenger RNA (mRNA) levels in vitro as well as in vivo. In both prepuberal and intact adult rats, serum testosterone concentrations were positively correlated with insulin mRNA levels and insulin concentration in serum. Testosterone deprivation after gonadectomy decreased both insulin gene expression and serum insulin concentration. Insulin mRNA levels were partially restored after 3 days of testosterone administration and serum insulin was 80% and 27% above baseline values at 5 and 7 days posttreatment. Primary cultured pancreatic islets treated with the sexual steroid increased about 80% insulin mRNA, as well as protein, and release. In transfected islets, testosterone increased the activity of the -410 bp rat insulin promoter I by 154%. These data demonstrate that testosterone has a direct effect upon pancreatic islet function by favoring insulin gene expression and release.
Asunto(s)
Insulina/biosíntesis , Insulina/genética , Regiones Promotoras Genéticas/genética , ARN Mensajero/biosíntesis , Testosterona/farmacología , Adenoviridae/genética , Animales , Northern Blotting , Cloranfenicol O-Acetiltransferasa/genética , Glucosa/metabolismo , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Plásmidos/genética , Ratas , Ratas Wistar , Testosterona/sangre , TransfecciónRESUMEN
We determined that the human papillomavirus type 18 (HPV18) regulatory region contains one functional GRE sequence that interacts with the glucocorticoid receptor. This sequence conferred a moderate hormonal activation to the HPV18 P105 promoter. Two modulators of glucocorticoid hormone activity, AP1 and hbrm, both involved in P105 transcription, were found not to interfere with this hormonal activation.
