Abstract
Nitric oxide (NO) is a novel and exciting compound with activities in many biologic systems, playing roles in neurotransmission, in immune system actuation, and as endothelial derived relaxation factor. Tumor necrosis factor (TNF) is believed to exert many of its effects by the elaboration of NO. The engine that catalyzes the production of NO. NO synthase, has been idenitfied in the adrenal gland but its function there is not known. Arginine analogs such as N-monomerthyl-L-argininc (L-NMMA) have been used as competitive inhibitors of NO synthase to investigate effects of NO. We have previously reported that TNF inhibits ACTH-stimulated glucocorticoid secretion, and we hypothesized that NO may mediate this effect of TNF. To test this hypothesis. We measured ACTH-stimulated corticosterone (CS) secretion from rat adrenal cells after 1 hour incubation with and without TNF in ihe presence or absence of 1 mM L-NMMA. Results are expressed as % baseline ± SEM (*p<0.01. control v L-NMMA).
Inhibition of NO production did not affect basal or stimulated CS secretion, but L-NMMA blocked TNF inhibition. These data implicate NO as a second messenger of TNF effect in the adrenal gland. This may have important implications in adrenal regulation, as the amount of glucocorticoid secreted may be dependent not onlu on ACTH but also the relative amounts of TNF and NO at any given time. This mechanism of control could be particularly relevant in stales of immune activation such as Gram negative sepsis, in which TNF and NO are known to be elevated.
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Zimmerman, P., Betz, J. & Poth, M. NITRIC OXIDE: A POTENTIAL MODULATOR OF ADRENAL HORMONE SECRETION. Pediatr Res 33 (Suppl 5), S21 (1993). https://doi.org/10.1203/00006450-199305001-00108
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DOI: https://doi.org/10.1203/00006450-199305001-00108