Involvement of vasoactive intestinal peptide on insulin-like growth factor I-induced proliferation of rat pituitary lactotropes in primary culture: evidence for an autocrine and/or paracrine regulatory system.
In previous studies we demonstrated that insulin-like growth factor I (IGF-I) induces pituitary vasoactive intestinal peptide (VIP) gene expression and secretion, and that IGF-I-induced prolactin (PRL) release is mediated by VIP. In this study, we investigate the mitotropic action of IGF-I and VIP on pituitary lactotropes, and their possible interplay in this effect. Cultured male rat pituitary cells were treated with rhIGF-I (10(-7)M) and/or VIP (10(-7)M) for 48 h. 5-Bromo-2'-deoxyuridine (BrdU) (10 microM) was added for labeling proliferation of pituitary cells. BrdU-labeling indices indicative of the proliferation rate of lactotropes were determined by double-labeling immunofluorescence staining for PRL and BrdU. Treatment with either IGF-I or VIP increased BrdU-labeling indices of lactotropes, but there was no further increase upon combined incubation with both factors, suggesting an interaction between the signal transduction pathways of IGF-I and VIP. VIP antiserum partially suppressed IGF-I-induced BrdU-labeling indices of lactotropes. We also investigated the intracellular signal transduction pathways in the action of IGF-I and VIP on the proliferation of lactotropes. Treatment of pituitary cells with an inhibitor of the mitogen-activated protein kinase (MAPK) pathway completely abolished IGF-I-induced lactotrope proliferation, whereas it partially suppressed VIP-induced BrdU-labeling indices. The protein kinase A (PKA) inhibitor, which abolished the mitogenic action of VIP, markedly suppressed IGF-I-induced lactotrope proliferation. These results indicate that both IGF-I and VIP stimulate lactotrope proliferation, and that IGF-I-induced lactotrope proliferation is partially mediated by VIP produced locally. Also, this study suggests that interactions between MAPK and cyclic adenosine 3',5'-monophosphate-PKA signaling pathways are implicated in the lactotrope proliferation induced by IGF-I and VIP.
Fernández
Miriam
M
Servicio de Endocrinología, Hospital Ramón y Cajal, Carretera de Colmenar, Madrid, Spain.
Sánchez-Franco
Franco
F
Palacios
Nuria
N
Sánchez
Isabel
I
Villuendas
Gemma
G
Cacicedo
Lucinda
L
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D014660:Vasoactive Intestinal Peptide; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases