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Endocrinology Vol. 138, No. 7 2740-2746
Copyright © 1997 by The Endocrine Society

ARTICLES

Transcriptional Regulation of Sertoli Cell Immediate Early Genes by Interleukin-6 and Interferon-{gamma} Is Mediated through Phosphorylation of STAT-3 and STAT-1 Proteins1

Shirzad Jenab and Patricia L. Morris

The Population Council (S.J., P.L.M.) and The Rockefeller University (P.L.M.), New York, New York 10021

Address all correspondence and requests for reprints to: Dr. Patricia L. Morris, Center for Biomedical Research, The Population Council and The Rockefeller University, 1230 York Avenue, New York, New York 10021.

The immediate early genes are regulated by a variety of extracellular signals, including pleiotropic cytokines. The effects of the testicular cytokines, interleukin-6 (IL-6) and interferon-{gamma} (IFN-{gamma}), on signal transducers and activators of transcription 3 and 1 (STAT-3 and STAT-1) and on c-fos gene expression in primary Sertoli cells are suggestive of their roles in differential function. Using the tyrosine phosphorylation inhibitor, genistein, and electrophoretic mobility shift assay, we show that IL-6 and IFN-{gamma} induce nuclear factor STAT-3 and STAT-1 DNA-binding activity to the sis-inducible element of c-fos in a genistein-dependent pathway. Quantitative solution hybridization, Northern blot, and nuclear run-on analysis show that differential induction of c-fos, junB, and c-myc messenger RNA (mRNA) by these cytokines occur at transcriptional levels. IL-6 stimulates c-fos mRNA levels by 6-fold while increasing junB levels by 2-fold. IFN-{gamma} increases c-fos message 2-fold, but has no effect on junB mRNA levels. Furthermore, genistein treatment blocks the induction of c-fos and junB gene expression, demonstrating that tyrosine phosphorylation of STAT proteins is involved in the cytokine regulation of the Sertoli immediate early genes. H7, a serine/threonine phosphorylation inhibitor, also blocks c-fos gene induction by IL-6 and IFN-{gamma}, but does not affect the DNA-binding activities of STAT-3 and STAT-1. Finally, IL-6 treatment of Sertoli cells (3–6 h) increases the amounts of activating protein-1 binding to activating protein-1 element and c-myc transcription.




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Copyright © 1997 by The Endocrine Society