title: 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.
abstract: 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.
authors.affiliation: Discovery Research Laboratories I, Takeda Chemical Industries, Ltd., Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: C
authors.initials: C
authors.lastname: Koyama
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: A
authors.initials: A
authors.lastname: Miyake
authors.forename: A
authors.initials: A
authors.lastname: Arimura
authors.forename: K
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: C495402:Adcyap1 protein, mouse; D015850:Interleukin-6; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D004247:DNA; D000242:Cyclic AMP