A Role of Pituitary Adenylate Cyclase Activating Polypeptide(PACAP) as a Regulator of Paracrine Interactions between Folliculo-Stellate Cells and Gonadotropes through the Control of Activin-Follistatin Interactions.

Katayama, Tetsuro; Nakashima, M.; Kyan, Hisako; Murakami, Noboru; Kuroda, Haruto

doi:10.1292/jvms.62.731

Cited by 15 publications

(7 citation statements)

References 55 publications

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“…Of particular note, PACAP has been shown to stimulate follistatin production by the pituitary folliculostellate cells. Because follistatin blocks activin-mediated stimulation of FSH␤ gene expression, PACAP indirectly blunts FSH␤ biosynthesis (11,15). The ultimate impact of PACAP on gonadotropin biosynthesis and secretion has not been fully elucidated; however, current consensus suggests that PACAP augments GnRH action although its effects are modest when present alone.…”

Section: --A P 1 P a C -A P 1 P A C -A P 1 M U T C R E P A C -C R E -mentioning

confidence: 99%

“…GnRH and PACAP interact within the hypothalamus and on both the gonadotropes and folliculostellate cells of the anterior pituitary to regulate gonadotropin biosynthesis and secretion(10,11,13,15,44,45). Although not depicted, PACAP receptors are also present on the other pituitary hormonesecreting cell types(43) forming a functional link between gonadotropes and gonadotrope-derived PACAP and nonreproductive endocrine systems.…”

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confidence: 99%

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GnRH Stimulates Expression of PACAP in the Pituitary Gonadotropes via Both the PKA and PKC Signaling Systems

Grafer

Thomas

Lambrakos

et al. 2009

Molecular Endocrinology

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Recent studies have demonstrated a clear role for pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of gonadotropin biosynthesis and secretion, both alone and in conjunction with GnRH. First defined as a hypothalamic releasing factor, PACAP subsequently has been identified in the gonadotrope subpopulation of the anterior pituitary gland, suggesting that PACAP may act as an autocrine-paracrine factor in this tissue. In initial studies, we determined that GnRH markedly stimulated endogenous PACAP mRNA levels and promoter-reporter activity in the mature gonadotrope cell line, LbetaT2. GnRH-stimulated rat PACAP promoter activity was blunted with deletion from position -915 to -402 and eliminated with further truncation to position -77 relative to the transcriptional start site. Site-directed mutagenesis demonstrated a functional requirement for a cAMP response element (CRE)-like site at position -205 and an activating protein-1 (AP-1)-like site at position -275, both of which bound CRE binding protein and AP-1 family members on EMSA. Treatment with pharmacological activators or inhibitors of second messenger signaling pathways implicated the protein kinase A, protein kinase C, and MAPK pathways in the GnRH response. In support of these in vitro data, we demonstrate that JunB binds to the rat PACAP gene promoter by chromatin immunoprecipitation assay and that small interfering RNA knockdown of JunB, cFos, and CRE binding protein factors blunts PACAP expression. In summary, these results further elucidate the complex functional interactions between PACAP and GnRH in the anterior pituitary. Specifically, these studies demonstrate that GnRH-stimulated PACAP gene expression is mediated via multiple signaling pathways acting on CRE/AP-1 sites in the proximal gene promoter. Because both PACAP and GnRH regulate gonadotropin biosynthesis and secretion, these results provide important insight into the critical fine tuning of gonadotrope function and, thereby, the maintenance of normal reproductive function.

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Section: --A P 1 P a C -A P 1 P A C -A P 1 M U T C R E P A C -C R E -mentioning

confidence: 99%

mentioning

confidence: 99%

GnRH Stimulates Expression of PACAP in the Pituitary Gonadotropes via Both the PKA and PKC Signaling Systems

Grafer

Thomas

Lambrakos

et al. 2009

Molecular Endocrinology

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“…Because IL-6 is involved in the differentiation of pituitary cells (Renner et al, 1998) and because it stimulates the release of various adenohypophysial hormones (Renner et al, 1998), several indirect effects of PACAP on endocrine pituitary cells may be mediated through activation of folliculostellate cells (Benter et al, 1995). In support of this notion, PACAP, added on cocultures of TtT/GF folliculostellate cells with rat anterior pituitary cells, significantly reduces the effect of activin-A on FSH secretion through follistatin release (Katayama et al, 2000).…”

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confidence: 92%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…In response to these systemic factors, FS cells synthesize and secrete cytokines and growth factors, such as follistatin, IL-6, annexin A1, transforming growth factor b3, and fibroblast growth factor 2 [12][13][14][15], that affect their own growth, that of the anterior pituitary endocrine cells, and the secretion of the anterior pituitary hormones, follicle-stimulating hormone, prolactin, and PMOC1 [4,6,[16][17][18][19]. Because FS cells are both the target and the source of cytokines, they are ideal candidates for the regulation of the function of the anterior pituitary.…”

Section: Introductionmentioning

confidence: 99%

Modulation of GJA1 Turnover and Intercellular Communication by Proinflammatory Cytokines in the Anterior Pituitary Folliculostellate Cell Line TtT/GF1

Fortin¹,

Pelletier²,

Meilleur³

et al. 2006

Biology of Reproduction

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Our previous studies have advanced the idea that the folliculostellate cell GJA1 (gap junction membrane channel protein alpha1; previously known as connexin 43)-mediated gap junctions contribute to the establishment of an intercellular network that regulates the paracrine messages and the endocrine response within the anterior pituitary. The folliculostellate cells are targets for growth factors and cytokines that modulate hormone secretion. Proinflammatory cytokines modulate the cell-to-cell communication in many tissues of the body. The present study measured the effect of the proinflammatory cytokines tumor necrosis factor and interleukin-1 on the GJA1-mediated intercellular communication, specifically the expression, localization, degradation, and phosphorylation status of GJA1 in the folliculostellate cell line TtT/GF. The GJA1 localized to the plasma membrane and to minute cytoplasmic vesicles in the perinuclear area. Using different antibodies that recognize distinctly the nonphosphorylated from the phosphorylated forms of GJA1, we showed that nonphosphorylated GJA1 in Ser-368 (NP-GJA1) localized chiefly in the cytoplasm, whereas GJA1 phosphorylated in Ser-368 (P-GJA1) localized to the plasma membrane in controls. The cytokine treatment transiently increased 1) GJA1, NP-GJA1, and P-GJA1 levels; 2) NP-GJA1 and P-GJA1 degradation by both the lysosomal and proteasomal pathways; and 3) cell-to-cell communication in TtT/GF cells. The results suggest that the cytokine-evoked, transient enhancement of folliculostellate cell-mediated intercellular communication contributes to the coordination of the response among folliculostellate cells.

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A Role of Pituitary Adenylate Cyclase Activating Polypeptide(PACAP) as a Regulator of Paracrine Interactions between Folliculo-Stellate Cells and Gonadotropes through the Control of Activin-Follistatin Interactions.

Cited by 15 publications

References 55 publications

GnRH Stimulates Expression of PACAP in the Pituitary Gonadotropes via Both the PKA and PKC Signaling Systems

GnRH Stimulates Expression of PACAP in the Pituitary Gonadotropes via Both the PKA and PKC Signaling Systems

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Modulation of GJA1 Turnover and Intercellular Communication by Proinflammatory Cytokines in the Anterior Pituitary Folliculostellate Cell Line TtT/GF1

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