DIFFERENTIAL CELLULAR-REGULATION OF PROOPIOMELANOCORTIN BY INTERLEUKIN-1-BETA AND CORTICOTROPIN-RELEASING HORMONE

Considerable evidence supports the existence of a bidirectional commun ication between the immune system and the hypothalamo-pituitary-adrena l (HPA) axis. In the present study, we examined the interleukin-1 beta (IL1 beta)-mediated regulation of pro-opiomelanocortin (POMC) at a ce llular level, from secretion to gene expression, using murine anterior pituitary corticotroph tumor (AtT20) cells as a model system. The reg ulatory effects of IL1 beta were compared to those of the classical PO MC regulator, corticotropin-releasing hormone (CRH). IL1 beta was foun d to evoke an early, preferential release of beta-lipotropin (beta LPH ) which was accompanied by elevations in POMC heteronuclear (hn)RNA an d c-fos and c-jun mRNAs. IL1 beta also elicited a late, preferential r elease of beta LPH which was associated with only an enhanced expressi on of POMC hnRNA. Additionally, IL1 beta stimulated an intermediate, p referential release of beta-endorphin (beta E) which was not accompani ed 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 elic ited a late, preferential beta E release which was associated with onl y an enhanced POMC hnRNA expression. These findings show that although both IL1 beta and CRH activate the corticotrophs, they elicit dramati cally different patterns in the regulation of the biochemical dynamics of POMC. Such distinct patterns of corticotroph activation in respons e to IL1 beta or CRH exposure in vivo would allow the pituitary not on ly to indicate that it has been activated, but also how it has been ac tivated. This characteristic may be critically important in the functi on of the HPA axis and in the interaction of the HPA axis with the imm une system.