Dexamethasone facilitates release of the neuropeptide alpha-MSH.
alpha-Melanocyte stimulating hormone (alpha-MSH) has important host defense properties, in part similar to those of corticosteroids. Previous research suggests that secretion of alpha-MSH and of ACTH are controlled separately. The relationship between release of alpha-MSH and the activity of the hypothalamic-pituitary-adrenal axis in the rabbit was examined by monitoring changes in circulating alpha-MSH, ACTH, and corticosterone in response to endotoxin and corticotropin-releasing hormone (CRH), both with and without dexamethasone pretreatment. Endotoxin (1 microgram/kg IV) did not cause alpha-MSH release, but it did increase plasma concentrations of ACTH and corticosterone. Similarly, CRH (1 and 10 micrograms/kg IV) did not affect plasma alpha-MSH, whereas it stimulated ACTH and corticosterone release. Dexamethasone pretreatment abolished the responses of ACTH and corticosterone to either stimulus and did not modify circulating alpha-MSH after CRH. In contrast, dexamethasone pretreatment did result in a significant increase in plasma alpha-MSH after a dose of endotoxin that was ineffective alone. These data indicate that corticosteroids can facilitate the release of alpha-MSH, a powerful anti-inflammatory hormone. Since corticosteroids are released with certain challenges, this facilitatory activity may be important to the host response.
Catania
A
A
First Medical Clinic, University of Milan, Italy.
Martin
L W
LW
Lipton
J M
JM
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D011817:Rabbits; D011863:Radioimmunoassay; D011897:Random Allocation; D000521:alpha-MSH / Q000378:metabolism*
D004731:Endotoxins; D000521:alpha-MSH; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone