Endogenous glucocorticoids and the induction and spread of monoarthritis in the rat.
Using mono- and bilateral tarsal arthritic models in the rat, we have previously shown increases in the expression of mRNAs encoding substance P and calcitonin gene-related peptide (CGRP) in primary sensory neurons innervating inflamed joints. Dorsal root ganglion (DRG) neuropeptide content in rats is altered by glucocorticoids, and since glucocorticoids regulate the expression of preprotachykinin (PPT) gene, the substance P precursor in other tissues, these effects may be mediated at the level of transcription. Indeed adrenalectomy potentiates disease in polyarthritis although the relationship to joint disease itself is unclear. Secretion of corticosterone in both mono- and bilaterally inflamed rats showed a loss of the normal diurnal nadir with no elevation of evening values. However, there were no changes in glucocorticoid target organs (adrenal gland, thymus and spleen) suggesting the stress was intermittent. Adrenalectomy in mono- and bilaterally inflamed rats did not significantly alter either the severity of inflammation or its spread. Bilaterally inflamed animals did, however, show reduced weight gain. Adrenalectomy had no effect on the induction of PPT and CGRP mRNA expression in innervating DRG neurons in monoarthritis (14 days after adjuvant injection), the unilateral increase in both PPT and CGRP mRNA expression in ADX animals being similar to SHAM arthritic rats. (PPT: ADX 140 +/- 13 left; 99 +/- 6 right % control; SHAM 160 +/- 22 left, 100 +/- 5 right % control. CGRP: ADX 177 +/- 6 left, 97 +/- 3 right % control; SHAM 147 +/- 21 left, 100 +/- 5 right % control).(ABSTRACT TRUNCATED AT 250 WORDS)
Donaldson
L F
LF
University of Edinburgh, Department of Medicine, Western General Hospital, Scotland, UK.
McQueen
D S
DS
Seckl
J R
JR
D000315:Adrenalectomy; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002940:Circadian Rhythm; D003345:Corticosterone / Q000378:metabolism; D015870:Gene Expression; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015320:Tachykinins / Q000235:genetics
D005938:Glucocorticoids; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D015740:Calcitonin Gene-Related Peptide; D003345:Corticosterone