Differential cellular regulation of pro-opiomelanocortin by interleukin-1-beta and corticotropin-releasing hormone.
Considerable evidence supports the existence of a bidirectional communication between the immune system and the hypothalamo-pituitary-adrenal (HPA) axis. In the present study, we examined the interleukin-1 beta (IL1 beta)-mediated regulation of pro-opiomelanocortin (POMC) at a cellular level, from secretion to gene expression, using murine anterior pituitary corticotroph tumor (AtT20) cells as a model system. The regulatory effects of IL1 beta were compared to those of the classical POMC regulator, corticotropin-releasing hormone (CRH). IL1 beta was found to evoke an early, preferential release of beta-lipotropin (beta LPH) which was accompanied by elevations in POMC heteronuclear (hn)RNA and c-fos and c-jun mRNAs. IL1 beta also elicited a late, preferential release of beta LPH which was associated with only an enhanced expression of POMC hnRNA. Additionally, IL1 beta stimulated an intermediate, preferential release of beta-endorphin (beta E) which was not accompanied by any changes in gene expression. In marked contrast to IL1 beta, CRH evoked an early, preferential beta E secretory response which was associated with elevations in POMC hnRNA and c-fos mRNA. CRH also elicited a late, preferential beta E release which was associated with only an enhanced POMC hnRNA expression. These findings show that although both IL1 beta and CRH activate the corticotrophs, they elicit dramatically different patterns in the regulation of the biochemical dynamics of POMC. Such distinct patterns of corticotroph activation in response to IL1 beta or CRH exposure in vivo would allow the pituitary not only to indicate that it has been activated, but also how it has been activated. This characteristic may be critically important in the function of the HPA axis and in the interaction of the HPA axis with the immune system.
Ruzicka
B B
BB
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720, USA.
Akil
H
H
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D015870:Gene Expression; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012313:RNA / Q000032:analysis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism
D007375:Interleukin-1; D001615:beta-Endorphin; D012313:RNA; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone