Neuropeptide TLQP-21, a VGF internal fragment, modulates hormonal gene expression and secretion in GH3 cell line.
In the present study we demonstrated that TLQP-21, a biologically 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, which upon treatment with epidermal growth factor develops a mammotrophic phenotype consisting of induction of prolactin expression and secretion, and inhibition of growth hormone. Here we determined for the first time that during mammotrophic differentiation, epidermal growth factor also induces Vgf gene expression and 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 growth hormone 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 the GH3 cell line toward a mammotrophic phenotype and suggest that it may exert a neuroendocrine role in vivo on lactotroph cells in the pituitary gland.
Institute of Cell Biology and Neurobiology and Institute of Translational Pharmacology, CNR Rome, Rome, Italy.
Pamela
P
Petrocchi Passeri
Laura
L
Biondini
Maria Patrizia
MP
Mongiardi
Nadia
N
Mordini
Stefania
S
Quaresima
Claudio
C
Frank
Mario
M
Baratta
Alessandro
A
Bartolomucci
Andrea
A
Levi
Cinzia
C
Severini
Roberta
R
Possenti
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011388:Prolactin / Q000096:biosynthesis; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C522412:TLQP-21 peptide; C062040:Vgf protein, rat; D004815:Epidermal Growth Factor; D011388:Prolactin; D002118:Calcium