PMID- 8380377
OWN - NLM
STAT- MEDLINE
DCOM- 19930205
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 132
IP  - 1
DP  - 1993 Jan
TI  - Prostaglandins mediate the adrenocorticotropin response to tumor necrosis factor 
      in rats.
PG  - 269-74
AB  - To determine whether prostaglandins (PGs) mediate the ACTH response to tumor 
      necrosis factor-alpha (TNF alpha), indomethacin (Indo; 0.1-1.0 mg/kg, iv) was 
      administered before TNF alpha (1 microgram, iv) in freely moving, alert rats. 
      While Indo alone did not affect plasma ACTH levels, it dose-dependently blocked 
      the ACTH response to TNF alpha. The highest dose of Indo abolished the ACTH 
      response to TNF alpha [peak plasma ACTH values (mean +/- SEM): buffer/buffer, 137 
      +/- 34 pg/ml; Indo/buffer, 115 +/- 31; buffer/TNF alpha, 469 +/- 77; Indo/TNF 
      alpha, 120 +/- 27] without modifying the ACTH response to CRF 1 microgram/kg, iv, 
      demonstrating that pituitary responsiveness was unaffected. Since it has been 
      reported that Indo elevates plasma corticosterone (B) levels, the effect of Indo 
      could reflect rapid negative feedback by B, rather than the involvement of PGs. 
      However, inhibition of ACTH secretion was shown to be dependent on the dose of 
      Indo, whereas plasma B levels were elevated to the same degree, independent of 
      the Indo dose. In addition, Indo failed to block the ACTH response to an 
      unrelated ACTH stimulus, insulin-induced hypoglycemia (area under response curve: 
      insulin alone, 31,131 +/- 2,794 pg/min.ml; Indo/insulin, 32,919 +/- 3,582 
      pg/min.ml). Finally, in adrenalectomized B-replaced rats, TNF alpha elevated ACTH 
      to levels similar to those seen in sham animals, and Indo inhibited these ACTH 
      responses to the same extent in both groups. Thus, Indo inhibited the ACTH 
      response to TNF alpha by a mechanism independent of B feedback. These results 
      indicate that acute systemic administration of TNF alpha stimulates ACTH 
      secretion through a PG-dependent mechanism.
FAU - Sharp, B M
AU  - Sharp BM
AD  - Endocrine-Neuroscience Research Laboratory, Minneapolis Medical Research 
      Foundation, Minnesota 55404.
FAU - Matta, S G
AU  - Matta SG
LA  - eng
GR  - DA-03977/DA/NIDA NIH HHS/United States
GR  - DA-04196/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Prostaglandins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Adrenocorticotropic Hormone/*metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Corticosterone/blood
MH  - Corticotropin-Releasing Hormone/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Indomethacin/administration & dosage/pharmacology
MH  - Insulin/pharmacology
MH  - Male
MH  - Prostaglandins/*physiology
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1210/endo.132.1.8380377 [doi]
PST - ppublish
SO  - Endocrinology. 1993 Jan;132(1):269-74. doi: 10.1210/endo.132.1.8380377.