Evidence for Daily Rhythms of the Expression of Proopiomelanocortin, Interleukin-1-Beta and Interleukin-6 in Adenopituitaries of Male Long-Evans Rats: Effect of Adjuvant Arthritis

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Abstract
Objective: Several interleukins (ILs) including IL-1β and IL-6 are produced in the anterior pituitary (AP) where they probably participate in the local regulation of hormone production. Immune challenge brings about the dysregulation of immune-endocrine interaction and enhanced the expression of pituitary IL-1β and IL-6. Little is known about regulation of their production, and therefore the purpose of the present work was to describe the relationship between circulating corticosterone and the mRNA expression of proopiomelanocortin (POMC), IL-1β and IL-6 in the AP during a 24-hour cycle in normal rats and rats with acute adjuvant arthritis (AA). Methods: Groups of intact male Long-Evans rats and rats 23 days after induction of AA kept on a 12-hour light/dark cycle (light on at 6:00 a.m.) were killed at 4-hour intervals starting at 2:00 p.m. Trunk blood was used for corticosterone determination by radioimmunoassay. Adenopituitaries were extracted for total RNA and the message of interest was quantitated by real-time PCR using specific primers and TaqMan probes. Parameters of rhythms were evaluated by cosinor analysis. Results: In normal rats, serum corticosterone showed a circadian rhythm with the peak at 6:00 p.m. and the nadir in the morning hours (p < 0.001). POMC mRNA in AP also showed a circadian rhythm (p < 0.05) which was inversely related to corticosterone levels. IL-1β and IL-6 expression in normal rats showed clear-cut daily rhythms (p < 0.001) with the nadirs in the dark period, in contrast to the corticosterone peak in plasma. In arthritic rats, rhythmic corticosterone secretion was suppressed with a plateau pattern of the rhythm. The mean POMC expression was higher than in controls, and the rhythm failed to be significant. IL-1β expression was suppressed by AA (p < 0.001) but the rhythm was still present (p < 0.05). The rhythmic pattern of IL-6 expression was similar to that of controls, but with higher mesor values (p < 0.05). Conclusion: These results suggest a regulatory relationship between circulating corticosterone and the expression of POMC, IL-1β and IL-6 in AP of normal rats. Arthritis induced a higher expression of POMC and IL-6 in the AP and a suppression of IL-1β mRNA during the 24-hour cycle which suggests the involvement of different regulatory mechanisms compared to normal conditions.

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