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)-l. 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-1β (3 µg/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-1β 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-1β. 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-1β stimulation of ACTH secretion in the rat.
We experienced an extremely unusual combination of Cushing's disease and corticosteroid-binding globulin (CBG) deficiency that has been reported in only one similar case to date. A 53-year-old woman presented at a medical clinic with clinical Cushing's disease. However, her plasma levels of adrenocorticotropin (ACTH) and cortisol were in the normal range. Six months later, during a second visit, a high urinary excretion of 17-hydroxycorticosteroids was found, but plasma ACTH and cortisol levels were normal again. Further investigation revealed a decreased CBG concentration. Free plasma cortisol levels were clearly elevated. Furthermore, the Cushing's disease of our patient was complicated by periodic secretion of ACTH and cortisol, with high or normal outputs of corticosteroids occurring alternately every 1-3 days, which explained the occasionally normal plasma ACTH and cortisol levels. A combination of a decreased serum CBG concentration and periodic secretion of ACTH can be an important pitfall in the diagnosis of Cushing's disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.