Testin induction: the role of cyclic 3',5'-adenosine monophosphate/protein kinase A signaling in the regulation of basal and lonidamine-induced testin expression by rat sertoli cells.
Results of previous in vitro and in vivo studies have illustrated that the expression of testin by Sertoli cells is tightly associated with the disruption of Sertoli-germ cell junctions. In the present study, treatment of rats with cadmium chloride (CdCl(2)), which disrupted the inter-Sertoli tight junctions, failed to induce any changes in testicular testin expression. In contrast, lonidamine, an antispermatogenic drug that rearranges the Sertoli cell membrane microfilament structure causing a disruption of Sertoli-germ cell adhesion junctions, induced a drastic increase in testicular testin expression when administered orally. Lonidamine-induced Sertoli cell testin expression involved both ongoing RNA and de novo protein synthesis. Basal testin expression remained stable during the 27-h incubation with actinomycin D but required de novo protein synthesis in vitro. An inhibitor of protein kinase A, Rp-cAMPS, caused a 50% inhibition of Sertoli cell testin expression at 10 microM within 24 h. A biphasic response was noted in testin expression when forskolin was included in the Sertoli cell culture, and high concentrations of cAMP analogues (1 mM) rapidly reduced testin expression. However, lonidamine can abolish the inhibitory effect of cAMP analogues on Sertoli cell testin expression. These results illustrate that the induction of testin expression may involve several signal transduction pathways.
Grima
J
J
Population Council, Center for Biomedical Research, New York, New York 10021, USA.
Cheng
C Y
CY
D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D000988:Antispermatogenic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005854:Germ Cells / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013723:Teratogens / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects
D000988:Antispermatogenic Agents; D007191:Indazoles; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D013723:Teratogens; C489180:testin protein, rat; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases; C016371:lonidamine