Effects of luteinizing hormone, follicle-stimulating hormone, and epidermal growth factor on expression and kinase activity of cyclin-dependent kinase 5 in Leydig TM3 and Sertoli TM4 cell lines

We examined the effects of luteinizing hormone (LH), follicle-stimulating h ormone (FSH), and epidermal growth factor (EGF) on the expression and kinas e activity of cyclin-dependent kinase 5 (Cdk5) in Leydig TM3 and Sertoli TM 4 cell lines. Hormonal regulation of the expression and activity of Cdk5 by using normal and hypophysectomized rat testes was also investigated to elu cidate its role. Cdk5 levels and kinase activity were significantly elevate d in TM3 cells that were grown in the presence of 7.5% serum, EGF, or LH an d were associated with an increase in testosterone production compared with controls. These increases were accompanied by an increase in proliferation of TM3 cells after treatment with serum or EGF but not with LH suggest tha t Cdk5 may be involved in cellular differentiation that is induced with LH treatment. In contrast, the presence of neither serum. EGF, nor FSH had a s ignificant effect on Cdk5 activity levels in the Sertoli TM4 cell line, and there was no correlation with proliferative activity or transferrin levels . A significant decrease in Cdk5 expression and activity were noted in rat testis after hypophysectomy compared with normal rat testis and is associat ed with a simultaneous decrease in testosterone and transferrin levels. Imm unohistochemical analysis revealed that Cdk5 was strongly expressed in the nuclei and cytoplasm of Leydig cells, Sertoli cells, spermatogonia, and per itubular cells of normal adult rat testis. After hypophysectomy, the patter n of Cdk5 staining differed markedly from that in normal rat testis and a p rofound reduction in staining of Cdk5 was observed in each tubule. Our resu lts suggest that LH and EGF influence and modulate Cdk5 expression and acti vity in Leydig TM3 cells and may, conceivably, be involved in signal transd uction cascades that are initiated by hormones or growth factors. Cdk5 in S ertoli TM4 cells is likely to possess some constitutive functions that are not affected by the cells' proliferation state. Moreover, Cdk5 is probably involved in the constitutive and hormonally stimulated activities of the ra t testis, in addition to its involvement in cell proliferation.