Tumor necrosis factor-alpha inhibits growth hormone secretion from cultured anterior pituitary cells

Anabolic proteins such as pituitary GH enhance the function of several immune cell types. The converse could also exist, that is communication from the immune cells to GH-producing somatotrophs. To test this hypothesis, tumor necrosis factor-alpha (TNF-alpha), a product of activated macrophages, was exposed to cultured rat pituitary cells, and GH release was monitored. TNF alpha inhibited basal and GH-releasing hormone-stimulated GH accumulation, with IC50 values of 170 U/ml (5.2 ng/ml) and 50 U/ml (1.5 ng/ml), respectively. This inhibition was first measured after 6 h of TNF alpha treatment, continued for at least 3 days, and was reversible. A number of measurements (e.g. trypan blue exclusion, chromium release, and GH cell content) yielded no signs of cytotoxicity to explain the inhibition. We conclude that TNF alpha can reduce basal and stimulated pituitary GH release in vitro.