Nitric oxide mediates the inhibitory effect of tumor necrosis factor-alpha on prolactin release.
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.
Theas
S
S
Centro de Investigaciones en Reproducción, Instituto de Biología Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
De Laurentiis
A
A
Candolfi
M
M
López
S L
SL
Carrasco
A E
AE
Zaldivar
V
V
Seilicovich
A
A
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D009569:Nitric Oxide / Q000819:agonists / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010902:Pituitary Gland / Q000166:cytology; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011388:Prolactin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat