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The Journal of Neuroscience, November 19, 2003, 23(33):10622-10632
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Development/Plasticity/Repair
Activation of erbB-1 Signaling in Tanycytes of the Median Eminence Stimulates Transforming Growth Factor 1 Release via Prostaglandin E2 Production and Induces Cell Plasticity
Vincent Prevot,
Anda Cornea,
Alison Mungenast,
Gregory Smiley, and
Sergio R. Ojeda
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, Oregon 97006
The activation of transforming growth factor (TGF )-erbB-1 and neuregulin-erbB-4 signaling pathways in hypothalamic astrocytes has been shown to play a key role in the process by which the neuroendocrine brain controls luteinizing hormone-releasing hormone (LHRH) secretion. Earlier studies suggested that tanycytes, an ependymoglial cell type of the median eminence, regulate LHRH release during the estrous cycle by undergoing plastic changes that alternatively allow or prevent direct access of the LHRH nerve terminals to the portal vasculature. Neither the molecules responsible for these plastic changes nor the underlying controlling mechanisms have been identified. Here we show that cultured tanycytes express erbB-1 and erbB-2, two of the four members of the erbB receptor family, and respond to TGF with receptor phosphorylation, release of prostaglandin E2 (PGE2), and a PGE2-dependent increase in the release of TGF 1, a growth factor previously implicated in the glial control of LHRH secretion. Blockade of either erbB-1 receptor signal transduction or prostaglandin synthesis prevented the stimulatory effect of TGF on both PGE2 and TGF 1 release. Time-lapse studies revealed that TGF and TGF 1 have dramatically opposite effects on tanycyte plasticity. Whereas TGF promotes tanycytic outgrowth, TGF 1 elicits retraction of tanycytic processes. Blockade of metalloproteinase activity abolished the effect of TGF 1, suggesting that TGF 1 induces tanycytic retraction by facilitating dissolution of the extracellular matrix. Prolonged (>12 hr) exposure of tanycytes to TGF resulted in focal tanycytic retraction, an effect that was abolished by immunoneutralization of TGF 1 action, indicating that the retraction was attributable to TGF -induced TGF 1 formation. These in vitro results identify tanycytes as targets of TGF action and demonstrate that activation of erbB-1-mediated signaling in these cells results in plastic changes that, involving PGE2 and TGF 1 as downstream effectors, mimic the morphological plasticity displayed by tanycytes during the hours encompassing the preovulatory surge of LHRH.
Key words: neuroendocrine; TGF ; TGF ; ependymoglial cells; LHRH; cell plasticity; hypothalamus
Received July 28, 2003;
revised September 23, 2003;
accepted September 24, 2003.
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