In the present study we demonstrated that TLQP-21, a biological active peptide derived from the processing of the larger pro-VGF granin, plays a role in mammotrophic cell differentiation. We used an established in vitro model, the GH3 cell line, that upon treatment with Epidermal Growth Factor (EGF) develops a mammotrophic phenotype consisting in induction of Prolactin expression and secretion, and inhibition of Growth Hormone (GH). Here we have determined for the first time that during mammotrophic differentiation, EGF also induces Vgf gene expression, increases VGF protein precursor processing and peptide secretion. After this initial observation we set out to determine the specific role of the VGF encoded TLQP-21 peptide on this model. TLQP-21 induced a trophic effect on GH3 cells and increased Prolactin expression and its own gene transcription without affecting GH expression. TLQP-21 was also able to induce a significant rise of cytoplasmic calcium, as measured by Fura2AM, due to the release from a thapsigargin-sensitive store. TLQP-21- dependent rise in cytoplasmic calcium was, at least in part, dependent on the activation of phospholipase followed by phosphorylation of PKC and ERK. Taken together, the present results demonstrate that TLQP-21 contributes to differentiation of GH3 cell line toward a mammotrophic phenotype and suggest that it may exert a neuroendocrine role in vivo on lactotroph cells in pituitary gland.
NEUROPEPTIDE TLQP-21, A VGF INTERNAL FRAGMENT, MODULATES HORMONAL GENE EXPRESSION AND SECRETION IN GH3 CELL LINE / Petrocchi, Pp; Biondini, L; Mongiardi, Mp; Quaresima S., Frank C; Baratta, Mario; Bartolomucci, A; Levi, A; Severini, C; Possenti, R.. - In: NEUROENDOCRINOLOGY. - ISSN 0028-3835. - 97:3(2013), pp. 212-224. [10.1159/000339855]
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