| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 91 === Digitalis glycosides (e.g. digoxin, digitoxin, ouabain) have been treated for the subjects with congestive heart failure via a mechanism involving the inhibition of Na+-K+ ATPase. Previous studies indicated that digoxin (DG) inhibits testosterone production by rat testicular interstitial cells through both in vivo and in vitro experiments. Digoxin and digitoxin, but not ouabain, inhibit the progesterone and pregnenolone secretion by rat granulosa cells and luteal cells, respectively. Although some investigations of the digitalis effects on endocrine systems have been reported, the effective mechanism of digitalis is still unclear. In the present study, both in vivo and in vitro studies of the effect of digitalis on adrenal function were examined. Zona fasciculata-reticularis cells were prepared from adrencortical tissues of ovariectomized rats. The cytotoxicity of digitalis were examined by the detection of lactate dehydrogenase (LDH). Then, the effects of digitalis on the basal and stimulated-corticorsterone production, the function of steroidogenic enzymes as well as the protein expression of cytochrome P450 side chain cleavage (P450scc) and steroidogenic acute regulated protein (StAR)(precursor carrier), and the mRNA expression of the StAR, were investigated. The corticosterone and pregnenolone levels in medium cultured from ZFR cells or in rat plasma extracted by diethyl ether were measured by radioimmunoassay. The expression of P450scc and StAR protein and mRNA determined by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. The results indicate that digoxin diminished plasma corticosterone level. Both digitoxin and digoxin inhibited the basal, cAMP analoge, Ca2+ activator and some of steroidogenic precursor-stimulated corticosterone production. However, digitalis had no cytotoxicity for ZFR cells. The digitalis did not influence the protein expression of P450scc and StAR, but both digitoxin and ouabain attenuated the mRNA expression of StAR. Taken together, we suggest that digitalis glycosides have an inhibitory effect on corticosterone production in ZFR cells of ovariectomized rats via an influence on cAMP-, Ca2+-pathway, competitive inhibition of P450scc enzyme and StAR mRNA expression.
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