EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON GROWTH-HORMONE AND INTERLEUKIN-6 MESSENGER-RNA IN OVINE PITUITARY-CELLS

The inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF-alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL-6 in a dose and time dependent manner. TNF-alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation. For IL-6, TNF-alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF-alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH-beta) subunit mRNA were unaffected by TNF-alpha. We conclude that TNF-alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed.