PARENT SESSION

(W762) THE EFFECT OF CORDYCEPIN ON STEROIDOGENESIS IN NORMAL MOUSE LEYDIG CELLS.

Poon, Song Ling¹, Tsai, Chih-Chien¹, Huang, Bu-Miin¹, ¹ National Cheng Kung University, Tainan, Taiwan R.O.C.

ABSTRACT- Cordycep sinensis (CS) is a precious drug in the treasure trove of traditional Chinese medicine. Studies have shown its multiple pharmacological activities, one of which is that it can enhance reproductive activity and restore impaired reproductive functions. We have previously demonstrated that CS alone could stimulate steroid production in both normal and tumor mouse Leydig cells. However, the precise substance in CS that plays the role in modulating the mechanism of steroidogenesis remains elusive. Cordycepin, or 3′deoxyadenosine, the analogue of adenosine, is a constituent isolated from the mycelia of CS. It has long been postulated that adenosine and its antagonists could influence the male reproductive system. Moreover, the mRNA expression of adenosine receptors has been detected in rat testis. Thus, the aim of this study is to investigate the effect and the regulatory mechanism of cordycepin on steroidogenesis in normal mouse Leydig cells. The results showed that cordycepin could stimulate testosterone production with dose- and time-dependent manners in normal mouse Leydig cells. By using specific receptor antagonist, cordycepin-stimulated testosterone production could be suppressed by A1, A_2a and A3 adenosine receptor antagonists, respectively. Moreover, PKA inhibitors, H89 & Rp-cAMPS, could suppress the cordycepin-stimulated testosterone production. These data suggest that cordycepin might act through the adenosine receptor to activate the PKA signaling pathway in order to stimulate normal mouse Leydig cell steroidogenesis. Cycloheximide, a protein synthesis inhibitor, inhibited the cordycepin-stimulated testosterone production, suggesting that de novo protein synthesis was required for cordycepin-stimulated steroidogenesis. Using Western blot analysis, cordycepin did induce the expression of Steroidogenic acute regulatory protein (StAR) in a dose-dependent manner. In conclusion, cordycepin could act through adenosine receptor and the PKA signaling pathway to induce the expression of StAR protein and thus stimulate the testosterone production in normal mouse Leydig cells.

KEY WORDS: cordycepin, Leydig cell, steroidogenesis, adenosine