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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0506v1 201/3/369    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kageyama, K. Articles by Suda, T. PubMed PubMed Citation Articles by Kageyama, K. Articles by Suda, T.

Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan¹ Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Oko-cho, Kohasu, Nankoku 783-8505, Japan

(Correspondence should be addressed to K Kageyama; Email: kkageyama{at}hkg.odn.ne.jp)

Corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. In the hypothalamic paraventricular nucleus (PVN), CRF, produced in response to stress, stimulates the release of ACTH from the anterior pituitary. ACTH then stimulates the release of glucocorticoids from the adrenal glands; circulating glucocorticoids are critical for recovery from stress conditions. Cytokines are also implicated in the regulation of CRF expression. Among them, interleukin (IL)-6 plays a role in the regulation of CRF. Factors other than glucocorticoids are likely to be involved in limiting the stimulation of CRF during stress. Suppressor of cytokine signaling (SOCS)-3 acts as a potent negative regulator of cytokine signaling. Little is known about the ability of the inhibitory signaling pathways to limit activation of the CRF gene in parvocellular PVN neurons. Hypothalamic 4B cells are useful for exploring the mechanisms, because these cells show characteristics of the parvocellular neurons of the PVN. In the present study, we examined whether SOCS-3 is regulated by IL-6 and cAMP in hypothalamic 4B cells. We also explored the involvement of SOCS-3 in the regulation of CRF gene expression. SOCS-3 was found to be regulated by IL-6 and via the cAMP/protein kinase A pathway in the hypothalamic cells. SOCS-3 knockdown increased IL-6- or forskolin-induced CRF gene transcription and mRNA levels. Therefore, SOCS-3, induced by a cAMP stimulant and IL-6, would be involved in the negative regulation of CRF gene expression in hypothalamic cells.