TUMOR-NECROSIS-FACTOR-ALPHA STIMULATES PROLACTIN-RELEASE FROM ANTERIOR-PITUITARY-CELLS - A POSSIBLE INVOLVEMENT OF INTRACELLULAR CALCIUM MOBILIZATION

We investigated the effects of tumor necrosis factor-alpha (TNF-alpha), a cytokine produced as one aspect of inflammatory reactions, on the intracellular free calcium concentration in single pituitary cells using a calcium-sensitive fluorescent dye, indo-1, and a digital imaging fluorescence microscopic system. TNF-alpha induced an increase in intracellular free calcium immediately after administration, reaching a peak after 30 sec and then returning to nearly the basal level after 120 sec in the pituitary cells. The cells responding to TNF-alpha constitute about 15% of the pituitary cell population, and these cells never responded to the hypothalamic releasing hormones TRH, GnRH, GH-releasing hormone, or CRH. To define the role of calcium in TNF-alpha-induced PRL release, dispersed pituitary cells were exposed to agents that modify TNF-alpha-induced calcium mobilization. Such calcium channel blockers as cobalt and verapamil decreased basal and TNF-alpha-induced PRL release. A low calcium medium also decreased TNF-alpha-induced PRL release. These data suggest that intracellular calcium mobilization may be involved in the process of TNF-alpha-induced PRL release.