Nitric oxide mediates the inhibitory effect of tumor necrosis factor-alphaon prolactin release

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that mark edly affects neuroendocrine functions. This cytokine is expressed in the an terior pituitary where its receptors are also present. Nitric oxide (NO) is synthesized in gonadotropes and folliculo-stellate cells of the anterior p ituitary. Since NO directly inhibits prolactin secretion, we investigated t he involvement of NO in the inhibitory effect of TNF-alpha. on prolactin re lease from anterior pituitary cells of female rats. The presence of L-NAME (1 mM an inhibitor of NO synthase (NOS), in the incubation medium significa ntly blunted the inhibition of prolactin release produced by TNF-alpha (50 ng/ml). TNF-alpha increased nitrite release to the incubation medium. The a ctivity of NOS as measured by [C-14]citrulline production was significantly enhanced when anterior pituitary cells were incubated with TNF-alpha for 8 h or more. Also, TNF-alpha induced iNOS gene expression in anterior pituit ary cells as assessed by reverse transcriptase-polymerase chain reaction. T he current results indicate that NO is involved in the inhibitory effect of TNF-alpha on prolactin secretion and that TNF-alpha induces iNOS transcrip tion and stimulates NO synthesis in anterior pituitary cells. Copyright (C) 2001 S. Karger AG, Basel.