Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs.
To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.
Moeniralam
H S
HS
Department of Endocrinology, University of Amsterdam, The Netherlands.
Endert
E
E
van Lanschot
J J
JJ
Sauerwein
H P
HP
Romijn
J A
JA
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004285:Dogs; D019446:Endotoxemia / Q000097:blood* / Q000503:physiopathology; D004731:Endotoxins / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male
D004731:Endotoxins; C044101:endotoxin, Escherichia coli; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone