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H Lin1 , YC Chiao1 *, JJ Chen1 *, SW Wang2 , PS Wang1 *
Dept. of Physiol., Natl. Yang-Ming Univ., Taipei, Taiwan, ROC. 1
Dept. of Physiol., Chang Gung Univ., Taoyuan, Taiwan, ROC. 2
Our previous study demonstrated that digoxin inhibits testosterone (T) secretion in rat testicular interstitial cells (TICs). Digitoxin (DI) is a cardiac glycoside with similar structure to digoxin and also a clinical medicine to patients with heart disease. In the present study, male rats were injected with DI, human chorionic gonadotropin (hCG), or DI plus hCG via jugular catheter. Blood samples were collected at 0, 30, and 60 min after the challenge. In the in vitro study, rat TICs were isolated and incubated with hCG, 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), or five steroidogenic precursors including 25-OH-cholesterol, pregnenolone, progesterone, 17-OH-progesterone, and androstenedione in the presence or absence of DI or ouabain (a selective Na+-K+-ATPase inhibitor) at 34°C for 1 h. The media and plasma samples were collected and analyzed for T. The effects of DI on cAMP levels in rat TICs were analyzed following priming with isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). Intravenous injection of DI decreased hCG-stimulated plasma T levels. Administration of DI in vitro resulted in an inhibition of both basal and hCG- as well as 8-Br-cAMP-stimulated release of T. In addition, DI diminished hCG-stimulated cAMP accumulation in TICs. DI inhibited the activity of cholesterol desmolase (P450scc) but failed to affect the activities of other steroidogenic enzymes. However, neither T secretion nor cAMP accumulation in rats TICs was affected by ouabain. These results suggest that the mechanism of the acute inhibitory effect of DI on T production in rat TICs involves a decrease of the activities of adenylyl cyclase and cholesterol desmolase and is independent of the action of Na+-K+-ATPase.
This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.