Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment

Endocrinology. 2006 Mar;147(3):1237-45. doi: 10.1210/en.2005-0981. Epub 2005 Dec 8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Butadienes / pharmacology
  • Cell Differentiation
  • Cells, Cultured
  • Chromones / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Follicle Stimulating Hormone / blood
  • Hot Temperature
  • Immunohistochemistry
  • Intermediate Filaments
  • Isoquinolines / pharmacology
  • Keratins / biosynthesis
  • Keratins / metabolism
  • Macaca fascicularis
  • Male
  • Microscopy, Confocal
  • Mitogen-Activated Protein Kinase 1 / biosynthesis*
  • Mitogen-Activated Protein Kinase 3 / biosynthesis*
  • Morpholines / pharmacology
  • Nitriles / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Sertoli Cells / cytology*
  • Sertoli Cells / enzymology
  • Signal Transduction
  • Sulfonamides / pharmacology
  • Temperature
  • Testis / metabolism
  • Time Factors


  • Butadienes
  • Chromones
  • Enzyme Inhibitors
  • Isoquinolines
  • Morpholines
  • Nitriles
  • Sulfonamides
  • U 0126
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Keratins
  • Follicle Stimulating Hormone
  • Phosphatidylinositol 3-Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide