Regulation and role of suppressor of cytokine signaling-3 in hypothalamic 4B cells.
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.
Kageyama
Kazunori
K
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan. kkageyama@hkg.odn.ne.jp
Hanada
Komaki
K
Iwasaki
Yasumasa
Y
Suda
Toshihiro
T
D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D005576:Colforsin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D053612:Janus Kinases; D017868:Cyclic AMP-Dependent Protein Kinases