A study on the role of circulating prostaglandin E2 in the adrenocorticotropin response to intravenous administration of interleukin-1beta in the rat.
It is almost generally agreed that prostaglandins (PGs), especially PGE2, may play a significant role in mediating corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) secretion by interleukin (IL)-1. The origin and site of action of PGE2 involved in this response appear to be within the brain, but the possibility has yet to be excluded that circulating PGE2, which increases after a systemic administration of IL-1, enters the brain to stimulate CRH and ACTH release. In this study, we attempted to answer the question utilizing in vivo experimental paradigms in conscious male rats. Intravenous bolus injection of recombinant human IL-1beta (3 mu g/kg) caused a prompt and robust rise in plasma ACTH (peak, 748 +/- 183 (-x +/- SE) pg/ml at 20 min), but this was not associated with a significant change in plasma PGE2 up to 120 min postadministration. Intravenous bolus injection of PGE2 at doses of 0.1 mg and 1.0 mg/kg BW resulted in dose-dependent significant elevations of the plasma ACTH with peak levels being 155 +/- 27 pg/ml (at 10 min) and 343 +/- 35 pg/ml (at 20 min), respectively. Peak PGE2 levels in the plasma which occurred 10 min after injecting either dose of PGE2 were 13,245 +/- 5,093 and 57,150 +/- 350 pg/ml, respectively. Thus the ACTH response which followed the plasma PGE2 levels of 13,000-57,000 pg/ml was even lower than the ACTH response to IL-1beta which did not cause a significant rise in the plasma PGE2. We conclude from these results that circulating PGE2 is not involved in the ACTH response to intravenous administration of IL-1beta. It is thus very likely that the source and site of action of PGE2 mediating the hormonal response are in the brain. However, this study does not exclude a possible role for other circulating PGs in the IL-1beta stimulation of ACTH secretion in the rat.
Watanobe
H
H
Third Department of Internal Medicine, Hirosaki University School of Medicine, Aomori, Japan.
Nasushita
R
R
Takebe
K
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D015232:Dinoprostone / Q000097:blood / Q000494:pharmacology*; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007375:Interleukin-1; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone