Site-related specificities of the control by androgenic status of adipogenesis and mitogen-activated protein kinase cascade/c-fos signaling pathways in rat preadipocytes.
In rats, castration induces a complete defective adipose conversion of preadipocytes from the epididymal fat depots (Lacasa, D., B. Agli, D. Noynarol, and Y. Giudicelli, 1995, Endocrine 3: 789-793). The aim of this study was to establish the eventual site-specificity of this effect as well as the mechanisms involved. Therefore, the influence of androgenic status on the Fos protein induction and the Raf/mitogen-activated protein (MAP) kinase kinase (MEK)MAP cascade, which are all required for adipose conversion of preadipocytes, was compared in proliferating and differentiated preadipocytes from femoral sc and deep intraabdominal (epididymal and perirenal) fat depots. In epididymal and perirenal proliferating preadipocytes, increased proliferation due to castration is associated with increased MAP kinase activity. However, higher immunoreactive levels of the upstream activators of MAP kinase, Raf-1 and MEK, were observed only in epididymal cells. Moreover, in vivo testosterone treatment corrected the effects of castration on Raf-1 but not on MEK and MAP kinase. MAP kinase activity was decreased during the course of adipogenesis. In differentiated cells, MAP kinase activity showed variations according to the anatomical origin of preadipocytes but not to the androgenic status. In contrast, MEK and Raf-1 immunoreactive levels were both sensitive to androgenic status but were differently affected depending on cell origin. Finally, the defective adipogenesis seen in epididymal preadipocytes from castrated rats was associated with reduced Fos protein induction in these cells, an alteration which was partly corrected by testosterone-treatment. Taken together, these results suggest that androgenic status affects adipogenesis from deep intraabdominal preadipocytes through alterations of some components of the MAP kinase cascade/Fos signaling pathways.
Lacasa
D
D
Service de Biochimie, INSERM CJF 94-02, Faculté de Medecine Paris-Ouest, Université René Descartes (Paris V) and Centre Hospitalier de Poissy, France.
Garcia
E
E
Henriot
D
D
Agli
B
B
Giudicelli
Y
Y
D017667:Adipocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D004822:Epididymis / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D005993:Glycerolphosphate Dehydrogenase / Q000032:analysis; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases; D009919:Orchiectomy; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D013739:Testosterone; D005993:Glycerolphosphate Dehydrogenase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases