THE INCREASE IN GROWTH-HORMONE SECRETION IN EXPERIMENTALLY-INDUCED ARTHRITIC RATS IS AN ADAPTIVE PROCESS INVOLVED IN THE REGULATION OF INFLAMMATION

In Sprague-Dawley rats, Freund-adjuvant-induced arthritis (AIA) result s in an increase in the amplitude of ultradian growth-hormone (GH)-sec retory episodes without modification of their frequency. This is most apparent at the time of maximal inflammation, i.e. 14-21 days after in oculation of the adjuvant. GH responsiveness to a maximal dose of clon idine (10 mu g/100 g body weight, BW), a secretagogue known to act at the hypothalamic level, is comparable in AIA and control rats. In cont rast, GH response to a maximal dose of GH-releasing hormone(GHRH, 1 mu g/100 g BW), a peptide acting directly on pituitary somatotropes, is greater in AIA than in control rats. Furthermore AIA affects significa ntly neither hypothalamic somatostatin and GHRH mRNA levels nor pituit ary GH content. In adult rats treated neonatally with monosodium gluta mate (MSG), a neurotoxin which destroys the majority of GHRH neurons o f the arcuate nucleus and reduces considerably plasma GH levels, clini cal symptoms observed 14 days after inoculation of the Freund adjuvant are more marked than in AIA. The MSG-treated rats exhibit in particul ar a significantly higher increase in hindpaw diameter. Pulsatile admi nistration of GH (40 mu g/day/rat, with successive periods of 2 h of G H and 4 h of mineral oil) restoring the endogenous GH-secretory patter n throughout the 15-day period of arthritis development prevents hindp aw diameter increase. These results indicate that the impact of AIA on GH regulation occurs at the pituitary but not the hypothalamic level and suggest that increased GH secretion observed in AIA rats is an ada ptive mechanism involved in the regulation of the inflammatory process .