Cordyceps sinensis mycelium activates PKA and PKC signal pathways to stimulate steroidogenesis in MA-10 mouse Leydig tumor cells.
Cordyceps sinensis (CS) mycelium stimulates steroidogenesis in MA-10 mouse Leydig tumor cells, but the mechanisms remain unclear. In this study, MA-10 cells were treated with different reagents in the presence or absence of CS (10 mg/ml) for 3 h to determine the mechanisms. Results illustrated that CS activated the Gsalpha protein subunit, but not Gialpha, to induce cell steroidogenesis. Moreover, PKA inhibitors inhibited 37% of CS-stimulated steroidogenesis, which demonstrated that CS might enhance the cAMP-PKA pathway to affect MA-10 cell steroidogenesis. Because of incomplete inhibition by PKA inhibitors, we also examined the PKC pathway. PKC inhibitor, phospholipase C inhibitor, and calmodulin antagonist blocked 35-52% of CS-stimulated steroidogenesis in MA-10 cells, strongly suggesting that CS had activated the PKC pathway. Co-treatment with PKA and PKC inhibitors abolished 61% of CS-stimulated steroid production, indicating that CS simultaneously activated PKA and PKC pathways. Moreover, CS induced the expression of steroidogenic acute regulatory (StAR) protein in dose- and time-dependent relationships, and PKA inhibitor, PKC inhibitor, or co-treatment with both inhibitors suppressed it. These data support that CS activates both PKA and PKC signal transduction pathways to stimulate MA-10 cell steroidogenesis.
Chen
Yung-Chia
YC
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Huang
Yuan-Li
YL
Huang
Bu-Miin
BM
D000818:Animals; D045744:Cell Line, Tumor; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology*; D032661:Cordyceps / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D051379:Mice; D025282:Mycelium / Q000737:chemistry*; D011374:Progesterone / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013736:Testicular Neoplasms / Q000378:metabolism*
D045424:Complex Mixtures; D011374:Progesterone