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 disrup tion of Sertoli-germ cell junctions. In the present study, treatment of rat s with cadmium chloride (CdCl2), which disrupted the inter-Sertoli tight ju nctions, failed to induce any changes in testicular testin expression. In c ontrast, 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 ex pression when administered orally. Lonidamine-induced Sertoli cell testin e xpression involved both ongoing RNA and de novo protein synthesis. Basal te stin 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 express ion at 10 muM within 24 h. A biphasic response was noted in testin expressi on when forskolin was included in the Sertoli cell culture, and high concen trations of cAMP analogues (1 mM) rapidly reduced testin expression. Howeve r, lonidamine can abolish the inhibitory effect of cAMP analogues on Sertol i cell testin expression. These results illustrate that the induction of te stin expression may involve several signal transduction pathways.