Evidence that MMP-2 and TIMP-2 are at play in the FSH-induced changes in Sertoli cells.
FSH has been shown to elicit in vitro changes in the Sertoli cell cytoskeleton through involving proteases, and cytochalasin-D mimics FSH. Testis extracts were screened (RT-PCR) for various metalloproteinases (MMPs), 20-day-old rat Sertoli cells were purified, cultured and treated with FSH, cytochalasin D and TNFalpha (to antagonize FSH action). Cell shape (phase-contrast microscopy) and levels for MMP-2 (gelatin zymography) and its inhibitor TIMP-2 (Northern and Western blot) were monitored. TNFalpha-treated cells spread readily and grew larger than FSH-treated cells. Cytochalasin-D mimicked FSH, and MMP-2 production and TIMP-2 gene expression were augmented. Interestingly, TNFalpha reversed FSH- and cytochalasin D-induced effects both on cell shape and on MMP-2 and TIMP-2. These effects occurred during the first 48 h of culture, when Sertoli cells migrated from the freshly dispersed aggregates, but not once cells were organized in monolayers. MMP-2 and TIMP-2 are likely involved in the FSH-induced changes in Sertoli cells.
Longin
Juliette
J
Inserm U329, Hopital Debrousse, 29 rue soeur Bouvier, 69322, Cedex 05, Lyon, France.
Le Magueresse-Battistoni
Brigitte
B
D000818:Animals; D048429:Cell Size; D015638:Cytochalasin D / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000502:physiology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019384:Nucleic Acid Synthesis Inhibitors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D015638:Cytochalasin D; D005640:Follicle Stimulating Hormone; D020778:Matrix Metalloproteinase 2