Abstract: 240

INHIBITION OF DIGOXIN AND DIGITOXIN ON PROGESTERONE PRODUCTION IN RAT LUTEAL CELLS.

SW Wang¹ , JJ Chen^{2 *}, SC Tsai^{2 *}, RL Wang² , YC Chiao^{2 *}, EJ Chien² , PS Wang^{2 *}
Dept. Physiol., Chang Gung Univ., Taoyuan, Taiwan, ROC. ¹
Dept. Physiol., Natl. Yang-Ming Univ., Taipei, Taiwan, ROC. ²

Both digoxin and digitoxin have been used clinically in the treatment of congestive heart disease via an inhibition of Na⁺, K⁺-ATPase activity. Administration of digoxin in male patients for 2 years decreased the plasma testosterone level. However, the effects of digitalis on female reproduction are still unknown. The present study was conducted to determine the role of digitalis in regulating steroidogenesis of progesterone (P) in rat luteal cells. Immature female rats were sacrificed 7 days after injection of pregnant mare serum gonadotropin (50 IU/rat) and human chorionic gonadotropin (hCG, 25 IU/rat). The luteal cells were harvested from enzyme treated corpora lutea and then incubated in Medium 199 with different concentrations of digoxin, digitoxin, and ouabain (a selective Na⁺, K⁺-ATPase inhibitor) with or without hCG (0.5 IU/ml) in the presence or absence of forskolin (an adenylyl cyclase activator), 8-bromo-adenosine 3':5'-cyclic momophosphate (8-Br-cAMP) or steroidogenic precursors including 25-OH-cholesterol and pregnenolone. The concentration of P in the media was measured by RIA. Administration of digoxin or digitoxin resulted in a dose-dependent inhibition of basal and hCG-stimulated release of P. The P production in response to forskolin or 8-Br-cAMP was inhibited by digoxin or digitoxin. Administration of pregnenolone, but not 25-OH-choloesterol, prevented the inhibition of P production by digoxin and digitoxin. Ouabain did not affect P production in rat luteal cells. These results suggest that digoxin and digitoxin reduce the production of P by luteal cells via a Na⁺, K⁺-ATPase-independent mechanism involving the inhibition of cAMP and P450_scc (desmolase) activities.

    This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.