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) results in an increase in the amplitude of ultradian growth-hormone (GH)-secretory episodes without modification of their frequency. This is most apparent at the time of maximal inflammation, i.e. 14-21 days after inoculation of the adjuvant. GH responsiveness to a maximal dose of clonidine (10 micrograms/100 g body weight, BW), a secretagogue known to act at the hypothalamic level, is comparable in AIA and control rats. In contrast, GH response to a maximal dose of GH-releasing hormone (GHRH, 1 microgram/100 g BW), a peptide acting directly on pituitary somatotropes, is greater in AIA than in control rats. Furthermore AIA affects significantly neither hypothalamic somatostatin and GHRH mRNA levels nor pituitary GH content. In adult rats treated neonatally with monosodium glutamate (MSG), a neurotoxin which destroys the majority of GHRH neurons of the arcuate nucleus and reduces considerably plasma GH levels, clinical symptoms observed 14 days after inoculation of the Freund adjuvant are more marked than in AIA. The MSG-treated rats exhibit in particular a significantly higher increase in hindpaw diameter. Pulsatile administration of GH (40 micrograms/day/rat, with successive periods of 2 h of GH and 4 h of mineral oil) restoring the endogenous GH-secretory pattern throughout the 15-day period of arthritis development prevents hindpaw 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 adaptive mechanism involved in the regulation of the inflammatory process.
Bluet-Pajot
M T
MT
Mounier
F
F
Slama
A
A
Videau
C
C
Kordon
C
C
Epelbaum
J
J
Calvino
B
B
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007031:Hypothalamus / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D010507:Periodicity; D010902:Pituitary Gland / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012970:Sodium Glutamate / Q000494:pharmacology
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D012970:Sodium Glutamate