Nitric oxide mediates the inhibitory effect of Tumor Necrosis factor-a on prolactin release.

S.THEAS,; A. DE LAURENTIIS,; M.CANDOLFI,; S.L.LÓPEZ,; A.E.CARRASCO,; V.ZALDIVAR,; A. SEILICOVICH

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2001 vol. 74 p. 82 - 86

0028-3835

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha (50 ng/ml). TNF-alpha increased nitrite release to the incubation medium. The activity of NOS as measured by [(14)C]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 pituitary cells as assessed by reverse transcriptase-polymerase chain reaction. The current results indicate that NO is involved in the inhibitory effect of TNF-alpha on prolactin secretion and that TNF-alpha induces iNOS transcription and stimulates NO synthesis in anterior pituitary cells.