DIFFERENTIAL ACTIVATION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT)-3 AND STAT-1 TRANSCRIPTION FACTORS AND C-FOS MESSENGER-RIBONUCLEIC-ACID BY INTERLEUKIN-6 AND INTERFERON-GAMMA IN SERTOLI CELLS

The regulation of expression of the immediate early gene c-fos messeng er RNA (mRNA) by interleukin-6 (IL-6) and interferon-gamma (IFN gamma) was investigated using primary Sertoli cells established from immatur e rat testis. Using electrophoretic mobility shift assay, we show that IL-6 and IFN gamma predominantly activate signal transducers and acti vators of transcription-3 and -1 proteins after 15 min of treatment, r espectively, whereas solution hybridization and Northern blot analyses show a differential induction of the c-fos mRNA by the two cytokines. IL-6 stimulated c-fos mRNA levels by 6-fold after 45 min; these level s returned to control values by 12 h of treatment. In contrast, IFN ga mma increased c-fos message 2-fold transiently, with RNA at the contro l level by 2 h after treatment. These cytokine-dependent inductions of c-fos mRNA levels were not affected by cyclohexamide, but were dimini shed by actinomycin D pretreatments, consistent with regulation at the transcriptional level. The differential activation of this testicular c-fos gene thus suggests multiple mechanisms and/or pathways of cytok ine regulation in Sertoli cells.