Nerve growth factor in the anterior pituitary: regulation of secretion.

beta-Nerve growth factor (NGF) is a 26-kilodalton protein that may have a broader distribution and set of functions than its name implies. Its functions are now linked to both the neuroendocrine and the immune systems. NGF immunoreactivity has been found in specific cell types in the anterior pituitary (AP) gland. The purpose of this study was to characterize further the NGF activity in AP cells, learn if it can be secreted, and determine the factors that may control secretion. NGF bioactivity was detected with assays of neurite outgrowth in PC12 tumor cells, and immunoreactivity was detected by an enzyme-linked immunoassay. AP cells secreted both bioactive and immunoreactive NGF at basal levels in vitro. In the enzyme-linked immunoassay, the anti-NGF recognized 2.5S NGF at a concentration of 0.10 pM, but it did not recognize brain-derived neurotrophic factor, neurotrophin-3 (NT-3), or NT-4, at concentrations as high as 10 nM. AP cells cultured for 6 days at 10(5) cells/200 microliters in DME plus 10% fetal calf serum secreted 1.5 +/- 0.16 pM NGF. Tests of substances that might regulate NGF secretion showed that interleukin-1 beta (IL-1 beta) at a concentration of 1 nM caused up to a 2.5 fold increase in NGF secretion. In addition, GH releasing hormone, tumor necrosis factor-alpha, basic fibroblast growth factor, and forskolin all caused an inhibition of NGF secretion below basal levels. The evidence demonstrates the presence and secretion of authentic NGF from AP cells. The fact that secretion is enhanced by IL-1 beta suggests that AP NGF may be a regulatory factor in the neuroendocrine-immune circuit.