AJP - Endocrinology and Metabolism, Vol 259, Issue 5 E672-E676, Copyright © 1990 by American Physiological Society
Tumor necrosis factor-alpha and interferon-gamma reduce prolactin release in vitro
P. E. Walton and M. J. Cronin
Genentech, South San Francisco, California 94080.
Prolactin binds to lymphocytes and monocytes and can modulate immune cell
function. It was postulated that proteins released from activated
macrophages and lymphocytes could directly influence prolactin release and
thus form an endocrine control loop during infection, tumor invasion, or
inflammation. This hypothesis was tested by exposing cultured rat anterior
pituitary cells to murine tumor necrosis factor-alpha (TNF-alpha) and/or
interferon-gamma (IFN-gamma) for 24 h before a 4-h test of cell function.
Overall prolactin accumulation during this first 24 h was inhibited by
TNF-alpha and markedly reduced by TNF-alpha plus IFN-gamma. In contrast,
thyroid-stimulating hormone levels were unchanged in these same media.
During the subsequent 4-h challenge, both cytokines reduced
thyrotropin-releasing hormone-stimulated prolactin release but had no
effect on inhibited prolactin release mediated by dopamine and somatostatin
receptors. Cellular viability (assessed by trypan blue and chromium release
assays) and prolactin cell content were unchanged after TNF-alpha or
IFN-gamma treatment. We conclude that both TNF-alpha and IFN-gamma have the
potential to act directly on anterior pituitary cells to slow the rate of
prolactin release.
