NF-kappaB participates in the corticotropin-releasing, hormone-induced regulation of the pituitary proopiomelanocortin gene.
Corticotropin-releasing hormone is a main regulator of mammalian stress response by stimulating pituitary proopiomelanocortin (POMC) gene expression, and thus adrenocorticotropic hormone (ACTH) secretion, which then causes glucocorticoid release from the adrenal. In a recent study in the pituitary corticotroph cell line AtT20, oxidative stress stimulated the activity of nuclear transcription factor B (NF-kappaB), whereas corticotropin-releasing hormone (CRH) inhibited both the constitutive and the oxidative stress-induced NF-kappaB DNA-binding activity. To further investigate the role of NF-kappaB on the CRH-induced pituitary POMC gene activation, AtT20 cells were transiently transfected with a POMC-luciferase construct mutated at an NF-kappaB binding site. After treatment with CRH, intracellular POMC-luciferase activity was significantly higher from the stimulation observed with transfection of the parental POMC-luciferase construct. In agreement with a previous report, CRH inhibited the constitutive NF-kappaB DNA-binding activity in AtT20 cells, as shown by electrophoretic mobility-shift assay, as soon as within 15 min of treatment. These effects of CRH were blocked by the CRH-R1 antagonist CP154,256. Our findings provide evidence that the regulation of corticotroph NF-kappaB activity by CRH is related to the activation of the pituitary POMC gene and, thus, may play an important role in stress response.
Karalis
Katia P
KP
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. katia.karalis@tch.harvard.edu
Venihaki
Maria
M
Zhao
Jie
J
van Vlerken
Lilian E
LE
Chandras
Christina
C
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D010902:Pituitary Gland / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics*
D017931:DNA Primers; D016328:NF-kappa B; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone