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This Article Accepted manuscript (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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kageyama, K. Articles by Suda, T. Search for Related Content PubMed PubMed Citation Articles by Kageyama, K. Articles by Suda, T.

K Kageyama, Department of Endocrinology, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan
K Hanada, Department of Endocrinology and Metabolism, Hirosaki University School of Medicine, Hirosaki, Japan
Y Iwasaki, Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Nankoku, Japan
T Suda, Department of Endocrinology, Hirosaki University School of Medicine, Hirosaki, Japan

Correspondence: Kazunori Kageyama, Email: kkageyama{at}hkg.odn.ne.jp

Abstract

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 adrenocorticotropic hormone (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 would 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 cyclic AMP 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 cyclic AMP/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 cyclic AMP stimulant and IL-6, would be involved in the negative regulation of CRF gene expression in hypothalamic cells.