PMID- 2161738
OWN - NLM
STAT- MEDLINE
DCOM- 19900713
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 126
IP  - 6
DP  - 1990 Jun
TI  - Interactions between tumor necrosis factor-alpha, hypothalamic 
      corticotropin-releasing hormone, and adrenocorticotropin secretion in the rat.
PG  - 2876-81
AB  - We studied the effects of tumor necrosis factor-alpha (TNF alpha), a 
      macrophage-derived pleiotropic cytokine produced during the inflammatory/immune 
      response, on the function of the hypothalamic-pituitary-adrenal (HPA) axis of the 
      rat. Intravenous injections of TNF alpha stimulated plasma ACTH and 
      corticosterone secretion in a dose-dependent fashion. This effect was inhibited 
      by a rat CRH antiserum that was administered to the rats 1 h before the TNF alpha 
      injections. This suggested that CRH is a major mediator of the HPA axis response 
      to TNF alpha. We subsequently evaluated the ability of TNF alpha to influence CRH 
      and ACTH secretion in vitro by explanted rat hypothalami in organ culture and by 
      dispersed rat anterior pituicytes in primary culture respectively. Hypothalami 
      were incubated for 40 min with graded concentrations of TNF alpha (10 pM to 1 
      microM). This cytokine stimulated CRH secretion in a dose-dependent fashion, with 
      an EC50 of 6.7 x 10 pM (P less than 0.05). Preincubation of hypothalamic explants 
      with dexamethasone, indomethacin (1 microM), eicosatetraynoic acid (10 microM), 
      or nordihydroguaiaretic acid (30 microM) resulted in inhibition of TNF 
      alpha-stimulated CRH secretion (P less than 0.05). Interestingly, 4-h incubation 
      with TNF alpha had no effect on ACTH secretion from rat anterior pituicytes at a 
      concentration of 10 nM. Higher concentrations of TNF alpha (100 nM and 1 microM), 
      however, elicited a dose-dependent increase in the ACTH concentration in the 
      medium. Our results suggest that TNF alpha represents one of the immune response 
      mediators that directly or via stimulation of other cytokines act as activators 
      of the HPA axis during immune/inflammatory reactions. This effect appears to be 
      glucocorticoid suppressible and eicosanoid mediated. The primary site of action 
      of TNF alpha appears to by the hypothalamic CRH-secreting neuron. Some pituitary 
      and adrenal effects of TNF alpha, however, cannot be excluded.
FAU - Bernardini, R
AU  - Bernardini R
AD  - Developmental Endocrinology Branch, National Institute of Child Health and Human 
      Development, National Institutes of Health, Bethesda, Maryland 20892.
FAU - Kamilaris, T C
AU  - Kamilaris TC
FAU - Calogero, A E
AU  - Calogero AE
FAU - Johnson, E O
AU  - Johnson EO
FAU - Gomez, M T
AU  - Gomez MT
FAU - Gold, P W
AU  - Gold PW
FAU - Chrousos, G P
AU  - Chrousos GP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Immune Sera)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1191-85-1 (5,8,11,14-Eicosatetraynoic Acid)
RN  - 7BO8G1BYQU (Masoprocol)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - 5,8,11,14-Eicosatetraynoic Acid/pharmacology
MH  - Adrenocorticotropic Hormone/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Corticosterone/metabolism
MH  - Corticotropin-Releasing Hormone/immunology/*physiology
MH  - Dexamethasone/pharmacology
MH  - Hypothalamus/drug effects/metabolism
MH  - Immune Sera/pharmacology
MH  - Indomethacin/pharmacology
MH  - Injections, Intravenous
MH  - Kinetics
MH  - Male
MH  - Masoprocol/pharmacology
MH  - Pituitary Gland/drug effects/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Tumor Necrosis Factor-alpha/administration & dosage/*pharmacology
EDAT- 1990/06/01 00:00
MHDA- 1990/06/01 00:01
CRDT- 1990/06/01 00:00
PHST- 1990/06/01 00:00 [pubmed]
PHST- 1990/06/01 00:01 [medline]
PHST- 1990/06/01 00:00 [entrez]
AID - 10.1210/endo-126-6-2876 [doi]
PST - ppublish
SO  - Endocrinology. 1990 Jun;126(6):2876-81. doi: 10.1210/endo-126-6-2876.