Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment.
Sertoli cells play a key role in triggering and regulating the process of spermatogenesis. Failure of a Sertoli cell to mature functionally will presumably render it incapable of supporting germ cell survival and development that appeared after puberty. Expression of cytokeratin 18 (ck-18) intermediate filaments indicates a state of undifferentiation usually observed in Sertoli cells of prepubertal testis. In this study we demonstrated that local testicular heat treatment of adult monkey with water at 43 C for 30 min once daily for 2 consecutive days was capable of activating reexpression of ck-18 in Sertoli cells, which was coincident with activation of ERK1/2 and Akt kinases. Using primary Sertoli cell culture isolated from adult monkey testis, we further confirmed that the heat treatment of the cells at 43 C could also induce ck-18 reexpression, which was similar to the in vivo treatment. ERK MAPK was also induced by the heat treatment in a time- and protein kinase A (PKA)-dependent manner. After blocking the ERK MAPK signaling pathway, an inhibition of ck-18 expression in the cultured Sertoli cells was observed, and this inhibitory effect was also detected by blocking the PKA activation. However, ck-18 activation in Sertoli cells remained unaltered when the phosphatidylinositol 3-kinase/Akt pathway was blocked. In conclusion, the heat treatment of adult monkey Sertoli cells are capable of inducing a reversible change in the Sertoli cells from an adult differentiated state to an immature-like dedifferentiated state through PKA-ERK MAPK-dependent pathways but not via the phosphatidylinositol 3-kinase/Akt pathway.
Zhang
Xue-Sen
XS
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 25, Bei Si Huan Xi Lu, Beijing 100080, China.
Zhang
Zhi-Hong
ZH
Jin
Xuan
X
Wei
Peng
P
Hu
Xiao-Qian
XQ
Chen
Min
M
Lu
Cui-Ling
CL
Lue
Yan-He
YH
Hu
Zhao-Yuan
ZY
Sinha Hikim
Amiya P
AP
Swerdloff
Ronald S
RS
Wang
Christina
C
Liu
Yi-Xun
YX
D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000097:blood; D006358:Hot Temperature; D007150:Immunohistochemistry; D007382:Intermediate Filaments; D007546:Isoquinolines / Q000494:pharmacology; D007633:Keratins / Q000096:biosynthesis / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology* / Q000201:enzymology; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013696:Temperature; D013737:Testis / Q000378:metabolism; D013997:Time Factors
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009025:Morpholines; D009570:Nitriles; D013449:Sulfonamides; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007633:Keratins; D005640:Follicle Stimulating Hormone; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide