Document Detail

Pituitary folliculo-stellate-like cell line (TtT/GF) responds to novel hypophysiotropic peptide (pituitary adenylate cyclase-activating peptide), showing increased adenosine 3',5'-monophosphate and interleukin-6 secretion and cell proliferation.
MedLine Citation:
PMID:  8404665     Owner:  NLM     Status:  MEDLINE    
Several studies have shown that folliculo-stellate cells (FS cells) in the anterior pituitary gland exhibit paracrine functions. Recently, we established a pituitary FS-like cell line, TtT/GF, which was derived from an isologously transplantable pituitary thyrotropic tumor line induced by radiothyroidectomy. In studies to examine the function of FS cells, we found that two forms of a novel hypophysiotropic peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), were potent activators of TtT/GF cells. Both the 27- and 38-amino acid forms of PACAP (PACAP-27 and PACAP-38) and vasoactive intestinal peptide (VIP) increased the levels of cAMP in TtT/GF cells in a similar dose-dependent manner. PACAP-27 and PACAP-38 specifically stimulated the proliferation of TtT/GF cells dose dependently, whereas VIP was ineffective. The minimal effective concentration of the PACAPs inducing cell proliferation was between 10(-8)-10(-7) M. However, PACAP-27 was much less potent than PACAP-38 in stimulating cell proliferation and DNA synthesis. PACAP-38, PACAP-27, and VIP all stimulated the release of interleukin-6 (IL-6) from TtT/GF cells. PACAP 38 (10(-8) M) stimulated IL-6 production effectively within 1 h of incubation, and the level attained at 8 h of cultivation (620 pg/ml) was nearly 10-fold that in the absence of PACAP-38 (60 pg/ml). PACAP-38 and VIP stimulated IL-6 secretion significantly at 10(-10)-10(-9) M in a bell-shaped manner; the maximum values were 10(-7) and 10(-8) M, respectively. On the other hand, IL-6 secretion stimulated by PACAP-27 became saturated at 10(-8) M, and the maximum value (320 pg/ml) was about 25% of that stimulated by PACAP-38 (1280 pg/ml). These findings obtained using TtT/GF cells as a model of FS cells suggest that PACAP acts as a hypophysiotropic factor, which targets FS cells and stimulates their proliferation, adenylate cyclase activation, and IL-6 secretion.
H Matsumoto; C Koyama; T Sawada; K Koike; K Hirota; A Miyake; A Arimura; K Inoue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  133     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1993-11-19     Completed Date:  1993-11-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2150-5     Citation Subset:  AIM; IM    
Discovery Research Laboratories I, Takeda Chemical Industries, Ltd., Ibaraki, Japan.
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MeSH Terms
Cell Division / drug effects*
Cyclic AMP / metabolism*
DNA / biosynthesis
Interleukin-6 / secretion*
Neuropeptides / pharmacology*
Pituitary Adenylate Cyclase-Activating Polypeptide
Pituitary Gland, Anterior / cytology,  drug effects,  metabolism*
Pituitary Neoplasms
Tumor Cells, Cultured
Vasoactive Intestinal Peptide / pharmacology
Reg. No./Substance:
0/Adcyap1 protein, mouse; 0/Interleukin-6; 0/Neuropeptides; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 37221-79-7/Vasoactive Intestinal Peptide; 60-92-4/Cyclic AMP; 9007-49-2/DNA

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