Increases in ornithine decarboxylase activity in the positive inotropism induced by androgens in isolated left atrium of the rat

It is well established that the intracellular receptors of androgens act as transcription factors upon their activation by androgen binding. However, a growing number of studies have associated androgens with rapid biological responses independent of their classical action mechanism. In this sense, 5 alpha- and 5 beta -dihydrotestosterone elicited a rapid positive inotropi sm in the isolated left atrium of the rat via cAMP-dependent mechanisms tha t may involve genomic effects. In addition, polyamines are mediators of sev eral biological actions including those acute and long-term effects induced by androgens in the heart. The present study analyzed the role of polyamin e synthesis in the cardiotonic effect of androgens in the left atrium of ma le Wistar rats, electrically stimulated (0.5 Hz, 5 ms and supramaximal volt age) and placed in an organ bath in 10 ml of Tyrode's solution. Incubation in the organ bath with an inhibitor of ornithine decarboxylase activity, al pha -difluoromethylornithine 10 mM, significantly decreased the positive in otropism induced by 5 alpha- and 5 beta -dihydrotestosterone (0.1-100 muM). This suggests that ornithine decarboxylase seems to be involved in androge n-induced positive inotropism. Furthermore, 6-min exposure to 5 alpha- or 5 beta -dihydrotestosterone significantly increased the activity of ornithin e decarboxylase from 61.81 +/- 7.53 (control) to 93.28 +/- 9.45 and 80.28 /- 12 pmol/h/mg of protein, respectively. Northern blot analysis showed tha t 5 alpha- and 5 beta -dihydrotestosterone did not modify the level of expr ession of the ornithine decarboxylase gene. Therefore, our results suggest that polyamine synthesis might be involved in the positive inotropism elici ted by androgens through the stimulation of ornithine decarboxylase activit y without changes in the expression of the ornithine decarboxylase gene. (C ) 2001 Elsevier Science B.V. All rights reserved.