Activation of erbB-1 Signaling in Tanycytes of the Median Eminence Stimulates Transforming Growth FactorΒ1 Release via Prostaglandin E[sub2] Production and Induces Cell Plasticity.

The activation of transforming growth factor α (TGFcα)- 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 TGFα with receptor phosphorylation, release of prostaglandin E[sub2] (PGE[sub2]), and a PGE[sub2]-dependent increase in the release of TGFβ[sub1], 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 TGFα on both PGE[sub2] and TGFβ[sub1] release. Time-lapse studies revealed that TGFα and TGFβ[sub1] have dramatically opposite effects on tanycyte plasticity. Whereas TGFα promotes tanycytic outgrowth, TGFβ[sub1] elicits retraction of tanycytic processes. Blockade of metalloproteinase activity abolished the effect of TGFβ[sub1], suggesting that TGFα induces tanycytic retraction by facilitating dissolution of the extracellular matrix. Prolonged (>12 hr) exposure of tanycytes to TGFα resulted in focal tanycytic retraction, an effect that was abolished by immunoneutralization of TGFβ[sub1] action, indicating that the retraction was attributable to TGFα-induced TGFβ[sub1] formation. These in vitro results identify tanycytes as targets. [ABSTRACT FROM AUTHOR]