The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of the GH gene in vitro

Morishita, Minako; Iwasaki, Yoshinobu; Onishi, Akira; Asai, Masato; Mutsuga, Naomi; Yoshida, Masanori; Oiso, Yutaka; Inoue, Kinji; Murohara, Toyoaki

doi:10.1677/jme.0.0310441

Cited by 19 publications

(13 citation statements)

References 39 publications

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“…PTX treatment similarly attenuated SRIF action in GH 4 cells overexpressing sst2 (Tentler et al 1997). In addition, PTX attenuated SRIFdependent inhibition of GHRH-induced GH in MtT/SGL somatotroph cells (Morishita et al 2003). sst5-specific inhibition of forskolin-stimulated cAMP accumulation was dependent on Ga o1 in human GH-secreting tumor primary cultures (Peverelli et al 2013).…”

Section: Cmentioning

confidence: 89%

“…The ability of SRIF to inhibit adenylate cyclase is G ai/odependent (Koch et al 1985, Tallent & Reisine 1992, Liu et al 1994, Morishita et al 2003. In GH 4 C 1 cells, SRIF-action is mediated specifically via Ga i2 (Liu et al 1994), as PTX suppresses SRIF-mediated inhibition of VIPinduced cAMP (Koch et al 1985).…”

Section: Cmentioning

confidence: 99%

“…Multiple factors and feedback loops regulate the release of SRIF from the hypothalamus and ultimately the control of GH secretion, including serum GH/IGF1 and glucose, as well as immobilization and exercise (Giustina & Veldhuis 1998). As SRIF inhibits GHRH-induced GH transcription and secretion by suppressing exocytosis of hormonecontaining granules (Patel & Srikant 1986, Tentler et al 1997, Morishita et al 2003, Farhy & Veldhuis 2004, SRIF-null mice were expected to exhibit the characteristics of GH excess. However, despite moderately elevated GH levels, serum IGF1 levels were slightly elevated; however, body length and weight and IGF1 levels were unchanged (Low et al 2001, Zeyda et al 2001.…”

Section: Gh Secretionmentioning

confidence: 99%

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Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

Eigler¹,

Ben-Shlomo²

2014

Journal of Molecular Endocrinology

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The somatostatin (SRIF) system, which includes the SRIF ligand and receptors, regulates anterior pituitary gland function, mainly inhibiting hormone secretion and to some extent pituitary tumor cell growth. SRIF-14 via its cognate G-protein-coupled receptors (subtypes 1-5) activates multiple cellular signaling pathways including adenylate cyclase/cAMP, MAPK, ion channel-dependent pathways, and others. In addition, recent data have suggested SRIF-independent constitutive SRIF receptor activity responsible for GH and ACTH inhibition in vitro. This review summarizes current knowledge on ligand-dependent and independent SRIF receptor molecular and functional effects on hormone-secreting cells in the anterior pituitary gland.

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Section: Cmentioning

confidence: 89%

Section: Cmentioning

confidence: 99%

Section: Gh Secretionmentioning

confidence: 99%

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Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

Eigler¹,

Ben-Shlomo²

2014

Journal of Molecular Endocrinology

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“…Since Gh gene expression is suppressed by IGF1 at the pituitary level (Goodyer et al 1984, Yamashita & Melmed 1986, the hypothalamic level (Abe et al 1983, Tannenbaum et al 1983) and somatostatin from the hypothalamus (Sugihara et al 1999, Morishita et al 2003, GH cells can be increased when the pituitary is released from suppression. However, addition of IGF1 did not decrease GH cell number in vitro, suggesting that IGF1 suppresses GH synthesis through the hypothalamus or somatostatin at day 10.…”

Section: Discussionmentioning

confidence: 99%

The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary

Hikake¹,

Hayashi²,

Iguchi³

et al. 2009

Journal of Endocrinology

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IGF1 knockout (IGF1KO) mice show a reduced number of prolactin (PRL) producing cells (PRL cells); however, the role of IGF1 in PRL cell proliferation and differentiation in immature mice is unclear. In this study, ontogenic changes in the percentages of PRL cells, GH producing cells (GH cells), and 5-bromo-2 0 -deoxyuridine (BrdU)-labeled cells in the anterior pituitary of male IGF1KO mice during the postnatal period were investigated. The percentage of PRL cells in IGF1KO mice was significantly lower at day 20 compared with that in wild-type (WT) mice, while GH cells in IGF1KO mice were significantly increased from day 10. From days 5 to 20, the percentage of BrdU-labeled cells in WT and IGF1KO mice was similar. PRL cells and GH cells are thought to originate from the same progenitor cells, therefore, PRL cells in IGF1KO mice are not able to differentiate because progenitor cells have already committed to be GH cells. However, IGF1, 17b-estradiol (E 2 ), epidermal growth factor (EGF), or IGF1 plus E 2 treatments increased the PRL cell number in the pituitaries in vitro of 10-day-old WT and IGF1KO mice. This fact suggests that these factors are involved in PRL cell proliferation and differentiation. In addition, the increase of PRL cells in IGF1KO mice stimulated by E 2 or EGF was less than that of WT mice. Thus, IGF1 plays a crucial role in PRL cell proliferation and differentiation in mouse pituitaries by regulating the differentiation of progenitor cells and mediating the actions of E 2 and EGF.

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“…These cells closely resemble primary pituitary somatotrophs, as their GH secretion is stimulated by growth hormone releasing hormone (GHRH) and inhibited by IGF-1 (31,33). The effect of IGF-1 treatment on the expression of GH mRNA levels was determined using quantitative RT-PCR (qRT-PCR) in both a concentration-dependent experiment for a 24-h treatment period and a time-dependent experiment with a constant IGF-1 concentration for up to 72 h. Figure 1A illustrates maximal suppression of GH mRNA at an IGF-1 concentration of 30 nM (P Ͻ 0.05) after 24 h. Subsequently, the effect of IGF-1 inhibition of GH mRNA expression relative to the 36B4 housekeeping control gene was demonstrated to be time dependent.…”

Section: Igf-1's Effect On the Gh Cbp And Pit-1/pou1f1 Mrna Levelsmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Mediates Negative Feedback to Somatotroph GH Expression via POU1F1/CREB Binding Protein Interactions

Romero

Pine-Twaddell

Sima

et al. 2012

Molecular and Cellular Biology

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Circulating insulin-like growth factor 1 (IGF-1) has been shown to act as a negative feedback regulator of growth hormone (GH) gene expression; however, the mechanism of this negative feedback is poorly understood. Activation and regulation of GH gene expression require the binding of the transcription factor POU1F1 to the GH promoter along with cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP). We investigate the role of CBP as a target of IGF-1 somatotroph regulation using the MtT/S somatotroph cell line. IGF-1 significantly inhibits basal GH mRNA levels but not POU1F1 levels. Chromatin immunoprecipitation assays demonstrate inhibition of CBP binding to the GH promoter after IGF-1 treatment. We hypothesized that IGF-1 receptor (IGF-1R) signaling disrupts the POU1F1/CBP complex to inhibit gene expression. In support, the use of a mutant CBP (S436A) construct, which lacks a critical phosphorylation site, leads to the loss of IGF-1 inhibition. The studies of CBP (S436A) knock-in mice show elevated serum GH levels, a greater response to GH releasing hormone (GHRH) stimulation along with lower weight gain, and decreased body fat. Our data confirm the inhibitory effects of IGF-1 on GH expression at the level of the promoter and provide evidence of CBP's role as a target of IGF-1R signaling.T he regulation of growth hormone (GH) is primarily influenced by the antagonistic actions of the hypothalamic hormones growth hormone releasing hormone (GHRH) and somatostatin (SRIF); however, it also well documented that the release of GH may be influenced by other factors and proteins produced both centrally and peripherally (2,5,8,14,45,47). Insulin-like growth factor 1 (IGF-1), which is produced primarily in the liver under the direct influence of GH, has an important role in not only somatic growth and metabolism but also negative feedback of GH release by targeting both the hypothalamus and pituitary (7,22,39,43). Several in vitro studies have demonstrated the ability of IGF-1 to decrease GH gene expression and hormone release (33,40,(52)(53)(54). Furthermore, transgenic animals with perturbations in the GH axis also demonstrate IGF-1's direct and indirect roles in regulation of the somatotroph (27,30,35,49,51). IGF-1R is a heterotetrameric glycoprotein comprised of two extracellular alpha subunits, which bind IGF-1, and two transmembrane beta subunits, which contain tyrosine kinase activity (13,22). Upon ligand binding to the receptor, two major pathways, the Ras/Raf/ mitogen-activated protein (MAP) kinase and the phosphatidylinositol 3-kinase (PI3 kinase) pathway, have been shown to play a role in mediating IGF-1 responses (16,17,24,26).Although in vitro and in vivo studies of IGF-1 negative feedback have proposed specific targets that ultimately affect GH expression and release, a mechanism of regulation at the cellular level remains unclear. We chose to first study IGF-1 regulation using an in vitro approach with the MtT/S cell line, which is an established rat tumor somatotroph cell line t...

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The effects of GH-releasing hormone/somatostatin on the 5'-promoter activity of the GH gene in vitro

Cited by 19 publications

References 39 publications

Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

The role of IGF1 on the differentiation of prolactin secreting cells in the mouse anterior pituitary

Insulin-Like Growth Factor 1 Mediates Negative Feedback to Somatotroph GH Expression via POU1F1/CREB Binding Protein Interactions

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