Pituitary Adenyl Cyclase-Activating Peptide: A Hypophysiotropic Factor That Stimulates Proopiomelanocortin Gene Transcription, and Proopio-melanocortin-Derived Peptide Secretion in Corticotropic Cells
作者:
Anne-Laurence Boutillier,
Dominique Monnier,
Bernard Koch,
Philippe Loeffler,
期刊:
Neuroendocrinology
(Karger Available online 1994)
卷期:
Volume 60,
issue 5
页码: 493-502
ISSN:0028-3835
年代: 1994
DOI:10.1159/000126786
出版商: S. Karger AG
关键词: Pituitary adenyl cyclase-activating peptide;cAMP;Protein kinase A;Adrenocorticotropin;Proopiomelanocortin;Corticotropin;Gene expression;Proopiomelanocortin
数据来源: Karger
摘要:
The biological effects of pituitary adenylate cyclase-activating peptide (PACAP) 27 and 38 on peptide secretion and gene regulation were studied in the mouse corticotrope-derived cell line AtT20. Treatment of these cells with PACAP 27/38 led to a dose-dependent increase in cAMP content and ACTH accumulation in the medium with an apparent ED50 value close to 10–9M The genomic effects of PACAP were first investigated by using a reporter gene containing a cAMP responsive element (CRE: TGACGTCA). PACAP 27/38 stimulate transcription from this construct and the effect is further increased when cells are cotreated with the phosphodiesterase inhibitor rolipram. Furthermore, we show by measuring nuclear heterologous proopiomelanocortin (POMC) RNA levels or by using a reporter gene containing the POMC promoter region, that PACAP stimulates POMC transcription. This transcriptional stimulation is mediated by the cAMP-dependent protein kinase (PKA) since genetic inactivation of PKA by a dominant inhibitory mutant of this enzyme completely abolished the effect of PACAP on POMC transcription. Finally, we show that the transcriptional stimulation of POMC by PACAP is repressed by the glucocorticoid receptor agonist dexamethasone. Taken together, these data suggest that PACAP is a hypophysiotropic hormone that exert similar if not identical functions as corticotropin-releasing hormone (CRH) on corticotrope cell
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