FARRAR, R.S.; RODNICK, K.J.; Idaho State University: Signaling pathways involved in steroid-induced inotropism of cardiac tissue from rainbow trout

Plasma levels of steroid hormones vary in salmonid fishes depending on reproductive status and stress levels. Similar to mammals, androgens promote dramatic sex differences in ventricle size and function during sexual maturation of salmon and trout. We have previously reported rapid, sex-dependent effects of testosterone, 11-ketotestosterone (11KT), cortisol and estradiol on promoting contractile performance of isolated cardiac tissue from rainbow trout. The purpose of the present study was to identify signaling pathways by which steroid hormones modulate cardiac function in fishes. Ventricles were removed from both male and female rainbow trout and four strips were cut from each ventricle. Strips were attached to isometric transducers, and stimulated to contract at 0.5 Hz with maximal voltage for 1 h prior to steroid additions. Pre-treatment with specific enzyme inhibitors GDP, DFMO and L-NAME were used to investigate the possible role of G-protein activation, polyamine synthesis and nitric oxide production, respectively. None of the inhibitors had independent effects on ventricle strips contractility. In males, the positive inotropism induced by physiological levels of testosterone, 11KT, and cortisol required signaling pathways involving synthesis of polyamines and nitric oxide. Cortisol and 17beta-estradiol, but not androgens, had similar effects in females and involved identical signaling pathways. Additional studies showed that the in vitro effects of steroids were absent if animals were anesthetized in buffered tricaine or benzocaine, and dependent upon steroid concentration and contraction frequency. SUMMARY: Although gonadal steroids and cortisol promote ventricular contractility in a sex-dependent manner, the underlying mechanism is conserved between the sexes and multifaceted.