The in vivo and in vitro stimulatory effects of cordycepin on mouse leydig cell steroidogenesis

Biosci Biotechnol Biochem. 2011;75(4):723-31. doi: 10.1271/bbb.100853. Epub 2011 Apr 22.


Cordycepin, a pure compound of Cordyceps sinensis (CS), is known as an adenosine analog. We have found that CS stimulated Leydig cell steroidogenesis. Here we investigated the in vivo and in vitro effects of cordycepin in primary mouse Leydig cell steroidogenesis. The results indicate that cordycepin increased the plasma testosterone concentration. Cordycepin also stimulated in vitro mouse Leydig cell testosterone production in dose- and time-dependent manners. We further observed that cordycepin regulated the mRNA expression of the A1, A2a, A2b, and A3 adenosine receptors in the mouse Leydig cells, and that antagonists of A1, A2a, and A3 suppressed testosterone production 20-50% testosterone production. Furthermore, Rp-cAMPS (cAMP antagonist) and Protein Kinase A (PKA) inhibitors (H89 and PKI) significantly decreased cordycepin-induced testosterone production, indicating that the PKA-cAMP signal pathway was activated by cordycepin through adenosine receptors. Moreover, cordycepin induced StAR protein expression, and H89 suppressed cordycepin-induced steroidogenic acute regulatory (StAR) protein expression. Conclusively, cordycepin associated with adenosine receptors to activate cAMP-PKA-StAR pathway and steroidogenesis in the mouse Leydig cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Deoxyadenosines / pharmacology*
  • Gene Expression Regulation / drug effects
  • Leydig Cells / cytology
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Organ Size / drug effects
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / metabolism
  • Purinergic P1 Receptor Antagonists / pharmacology
  • Receptors, Purinergic P1 / genetics
  • Signal Transduction / drug effects
  • Steroids / biosynthesis*
  • Testosterone / blood


  • Deoxyadenosines
  • Phosphoproteins
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Steroids
  • steroidogenic acute regulatory protein
  • Testosterone
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • cordycepin