Hypothalamic action of cachectin to alter pituitary hormone release.
Cachectin (tumor necrosis factor, TNF) is a macrophage hormone which is released during infection and after injection of bacterial lipopolysaccharides. We have already demonstrated that the peptide has direct action on the pituitary to alter pituitary hormone release in vitro. To evaluate its action in vivo, we injected it into the third ventricle (3V) of conscious, male rats and measured its effect on various anterior pituitary hormones. The peptide produced an elevation in rectal temperature measurable on first measurement at 1 hour postinjection which was maintained for 3 hours. The maximal increase in body temperature was 1-1.5 degrees C and maximal effect was obtained by a dose as low as 1 ng (0.3 pmol) of the peptide. Preinjection of indomethacin into the 3V 1 hour prior to injection of TNF completely blocked the effect on body temperature without producing an alteration in rectal temperature itself which suggests that the elevation in body temperature may be mediated by prostaglandins. Following the intraventricular injection of various doses of TNF, there was no significant effect on plasma adrenocorticotropin (ACTH) except with the highest, 100 ng dose tested, which evoked a small but significant increase in plasma ACTH with a delay of 1 to 2 hours. Thus, the dose necessary to release ACTH was much higher than that required to elevate body temperature. The effect was no longer significant in indomethacin-pretreated animals suggesting a role for prostaglandins in the effect. This highest dose of intraventricularly administered TNF also produced a relatively modest, but significant, delayed increase in plasma GH.(ABSTRACT TRUNCATED AT 250 WORDS)
Rettori
V
V
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Milenkovic
L
L
Beutler
B A
BA
McCann
S M
SM
D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D010908:Pituitary Hormones, Anterior; D014409:Tumor Necrosis Factor-alpha