Lipopolysaccharide- and tumor necrosis factor-alpha-induced changes in prolactin secretion and dopaminergic activity in the hypothalamic-pituitary axis.
Bacterial lipopolysaccharide (LPS) affects pituitary hormone secretion, including prolactin release, by inducing synthesis and release of cytokines such as tumor necrosis factor-alpha (TNF-alpha). Since prolactin is mainly under tonic inhibitory control of dopamine, we investigated the effect of LPS and TNF-alpha on the hypothalamic-pituitary dopaminergic system. LPS (100-250 microg/rat, i.p.) decreased serum prolactin levels after 1 or 3 h. Sulpiride, a dopaminergic antagonist, increased serum prolactin and blocked the inhibitory effect of LPS. LPS increased hypothalamic dopamine and DOPAC concentrations and the DOPAC/dopamine ratio both in mediobasal hypothalamus and the posterior pituitary. LPS also enhanced dopamine and DOPAC concentration in the anterior pituitary. LPS elevated plasma levels of epinephrine, norepinephrine and dopamine but it did not modify the concentration of epinephrine or norepinephrine in the tissues studied. The administration of TNF-alpha (i.c.v., 1 h, 100 ng/rat) decreased serum prolactin but did not affect plasma catecholamine levels. TNF-alpha did not modify the DOPAC/dopamine ratio in hypothalamus or posterior pituitary but increased dopamine and DOPAC concentrations in the anterior pituitary. Incubations of hypothalamic explants showed that TNF-alpha did not modify in vitro basal dopamine release and reduced K(+)-evoked dopamine release. On the contrary, incubations of posterior pituitaries showed that TNF-alpha significantly increased basal and K(+)-evoked dopamine release. These results indicate that LPS and TNF-alpha increase dopamine turnover in the hypothalamic-pituitary axis. This increase in dopaminergic activity could mediate the inhibitory effect of LPS and TNF-alpha on prolactin release. Furthermore, the increase in dopaminergic activity elicited by LPS could be mediated by an increase in hypothalamic TNF-alpha during endotoxemia.
De Laurentiis
Andrea
A
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Pisera
Daniel
D
Caruso
Carla
C
Candolfi
Marianela
M
Mohn
Claudia
C
Rettori
Valeria
V
Seilicovich
Adriana
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001424:Bacterial Infections / Q000097:blood / Q000276:immunology*; D004298:Dopamine / Q000097:blood / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D006966:Hyperprolactinemia / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013026:Space Flight; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015102:3,4-Dihydroxyphenylacetic Acid; D011388:Prolactin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine