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

Abstract

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