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Endocrinology Vol. 142, No. 4 1442-1447
Copyright © 2001 by The Endocrine Society

ARTICLES

Testosterone Effect on Insulin Content, Messenger Ribonucleic Acid Levels, Promoter Activity, and Secretion in the Rat1

Sumiko Morimoto2, Cristina Fernandez-Mejia, Guillermo Romero-Navarro, Nestor Morales-Peza and Vicente DÍaz-Sánchez

From the Department of Reproductive Biology, National Institute of Medical Sciences and Nutrition Salvador Zubiran (S.M., V.D.S.), Nutritional Genetics Unit (C.F.M., G.R.N.), Biomedical Research Institute, National University of México, National Institute of Cancer (N.M.P.), Tlalpan 14000, D.F. México City, México

Address all correspondence and requests for reprints to: Vicente Díaz-Sánchez, M.D., Departamento de Biología de la Reproducción. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Vasco de Quiroga 15, Tlalpan 14000, D.F. México City, México. E-mail: vidisa{at}quetzal.innsz.mx

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.




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