Growth Hormone Receptor Binding Protein in Rat Anterior Pituitary

Mertani, Hichem C.; Waters, Michael J.; Jambou, Ronan; Gossard, Françis; Morel, Gérard

doi:10.1159/000126695

Cited by 36 publications

(19 citation statements)

References 36 publications

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“…It is tempting to speculate that GH may negatively regulate its own secretion; however, evidence for a non-IGF-mediated autocrine pituitary feedback by GH is indirect (4,61,62). The GH receptor is expressed in rat and human anterior pituitary and binds and internalizes radiolabeled GH, suggesting a role for GH to regulate its secretion from the pituitary (63)(64)(65)(66). However, the signaling of the GH receptor in pituitary cells has not been investigated.…”

Section: Gh-induced Coupling To G Proteins and Lipid Signaling-mentioning

confidence: 99%

Growth Hormone-induced Diacylglycerol and Ceramide Formation via Gαi3 and Gβγ in GH4 Pituitary Cells

Liu

Robillard

Banihashemi

et al. 2002

Journal of Biological Chemistry

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Growth hormone (GH) secretion is regulated by indirect negative feedback mechanisms. To address whether GH has direct actions on pituitary cells, lipid signaling in GH 4 ZR 7 somatomammotroph cells was examined. GH (EC 50 ‫؍‬ 5 nM) stimulated diacylglycerol (DAG) and ceramide formation in parallel by over 10-fold within 15 min and persisting for >3 h. GH-induced DAG/ceramide formation was blocked by pertussis toxin (PTX) implicating G i /G o proteins and was potentiated 1.5-fold by activation of G i /G o -coupled dopamine-D2S receptors, which had no effect alone. Following PTX pretreatment, only PTX-resistant G␣ i 3, not G␣ o or G␣ i 2, rescued GHinduced DAG/ceramide signaling. GH-induced DAG/ceramide formation was also blocked in cells expressing G␤␥ blocker GRK-ct. In GH 4 ZR 7 cells, GH induced phosphorylation of JAK2 and STAT5, which was blocked by PTX and mimicked by ceramide analogue C2-ceramide or sphingomyelinase treatment to increase endogenous ceramide. We conclude that in GH 4 pituitary cells, GH induces formation of DAG/ceramide via a novel G␣ i 3/ G␤␥-dependent pathway. This novel pathway suggests a mechanism for autocrine feedback regulation by GH of pituitary function.Pituitary somatotrophs synthesize and secrete GH, 1 which acts at the liver and other tissues to stimulate IGF formation, promoting somatic growth throughout the body (1, 2). Secretion of GH is stimulated by hypothalamic GH-releasing hormone and inhibited by the hypothalamic tetradecapeptide somatostatin and by IGF. In addition, somatostatin agonists (e.g. octreotide) and dopamine-D2 agonists (e.g. bromocryptine) are used clinically to treat acromegaly (a syndrome produced by hypersecretion of GH) and to inhibit somatomammotroph growth and GH production (3). Negative feedback via autocrine actions of GH at the pituitary has been postulated (4) but is yet to be clearly demonstrated.The GH receptor is a member of the type I cytokine receptor superfamily, related to PRL and erythropoietin receptors that homodimerize to initiate signaling (5). The GH receptor signals through the JAK2 tyrosine kinase-signal transducer and activator of transcription 5 (STAT5) transcription factor pathway to induce gene expression (6 -9). Phosphorylation on residue Tyr-694 by JAK2 is obligatory for STAT5 activation (10). The two STAT5 variants, STAT5a and STAT5b, have 90% identical protein sequences and are independently regulated and activated in various cell types (11). Studies using STAT5a or STAT5b knockout mice have demonstrated that STAT5b, but not STAT5a, is required for GH-induced regulation of IGF1 and sex-specific steroidogenic enzymes in liver (11-13). While STAT5 activation is implicated in many GH actions, other signaling pathways not involving STAT5 appear to be recruited for GH-induced stimulation of other pathways including MAPK phosphorylation and phosphatidyl inositol 3Ј-kinase or protein kinase C activation (14, 15) in a cell type-dependent manner (16). Ceramide is a novel second messenger implicated in regulation of cell differentiation,...

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Section: Gh-induced Coupling To G Proteins and Lipid Signaling-mentioning

confidence: 99%

Growth Hormone-induced Diacylglycerol and Ceramide Formation via Gαi3 and Gβγ in GH4 Pituitary Cells

Liu

Robillard

Banihashemi

et al. 2002

Journal of Biological Chemistry

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“…Observations were done using a Philips CM120 electron microscope (Centre Technologique des Microstructures, UCBL Lyon). Quantification of gold particles was determined in immunohistologically characterized lactotropes (n >30) as previously described [31]. Only photographs passing through the nucleus were used for quantification and results are expressed as the number of gold particles per area unit of cell section.…”

Section: Methodsmentioning

confidence: 99%

Cloning, Expression and Regulation of Chicken Ovalbumin Upstream Promoter Transcription Factors (COUP-TFII and EAR-2) in the Rat Anterior Pituitary Gland

Raccurt¹,

Smallwood²,

Mertani³

et al. 2005

Neuroendocrinology

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Chicken ovalbumin upstream promoter transcription factors (COUP-TF)-II (NR2F2) and EAR-2 (NR2F6) are structurally related orphan members of the nuclear receptors superfamily. There are growing evidences that these factors play important roles during processes of differentiation and proliferation of several tissues. To better understand their role in the differentiated adult rat pituitary gland, we cloned COUP-TFII and EAR-2 cDNAs from an anterior pituitary cDNA library. Subsequently, we raised and characterized specific antibodies to the N-terminal domain of both nuclear receptors. We next examined their cellular and subcellular distribution in the pituitary gland and determined their regulation during pregnancy. COUP-TFII and EAR-2 pituitary genes display, respectively, 90 and 100% homologies with their human and mouse homologues. Cellular expression of both nuclear receptors was mainly detected in the lactotropes of male and female rats, with a prominent distribution in the nuclear compartment for EAR-2, and interestingly both proteins were significantly upregulated in pituitaries of pregnant vs. cycling female rats. Thus, our results have characterized cloning of rat pituitary COUP-TFII and EAR-2 genes, demonstrated that they are both specifically expressed in lactotropes, and strongly suggested that they may play an important role in modulating prolactin (PRL) gene expression during pregnancy.

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“…The clinical observations are supported by histological studies identifying GH and IGF1 receptors in Leydig, Sertoli, and germ cells as well as in the accessory reproductive glands (1,9,10). A central hypothalamic/pituitary effect of GH has also been suggested including the stimulation of gonadotropin secretion (1,11,12,13). Finally, GH/IGF1 activity mayA common genetic polymorphism is deletion of the entire exon 3 sequence (GHRd3 isoform).…”

Section: Introductionmentioning

confidence: 91%

Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

Andreassen

Jensen

Jørgensen

et al. 2014

European Journal of Endocrinology

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Introduction: GH activity may be involved in male reproductive function. A common genetic polymorphism in the gene encoding the GH receptor (GHR) results in deletion of the entire exon 3 sequence (GHRd3 isoform). The short GHRd3/d3 isoform seems more sensitive compared with full-length receptors (GHRfl/fl). Aim: To investigate the associations between GH activity, evaluated by exon 3 GHR polymorphism, and serum IGF1 vs reproductive hormones, semen quality, and pre-and postnatal growth in healthy young males (nZ838, mean age: 19.4 years). Results: Compared with GHRfl/fl homozygous individuals (nZ467) GHRd3/d3 homozygous individuals (nZ69) tended to have larger semen volume (3.2 (2.4-4.3) vs 3.6 (2.6-4.7) ml, PZ0.053) and higher serum inhibin-B levels (208 pg/ml (158-257) vs 227 pg/ml (185-264), PZ0.050). Semen quality, levels of gonadotropins, testosterone, estradiol, sex hormone-binding globulin, and IGF1 were not associated with GHRd3 genotype. A twofold increase in serum IGF1 was associated with a 13% (4-23) increase in calculated free testosterone (PZ0.004). By contrast IGF1 was inversely associated with serum inhibin-B (PZ0.027), but showed no associations to semen quality. GHR genotype and serum IGF1 were not associated with size at birth or final height. Conclusions: GHRd3 polymorphism seemed only to have a weak influence on male reproductive function of borderline significance. The sensitive GHRd3/d3 genotype may slightly increase testicular function, as evaluated by semen volume and levels of inhibin-B, but does not seem to influence Leydig cell steroidogenesis. GHR genotype did not influence pre-and postnatal growth.

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Growth Hormone Receptor Binding Protein in Rat Anterior Pituitary

Cited by 36 publications

References 36 publications

Growth Hormone-induced Diacylglycerol and Ceramide Formation via Gαi3 and Gβγ in GH4 Pituitary Cells

Growth Hormone-induced Diacylglycerol and Ceramide Formation via Gαi3 and Gβγ in GH4 Pituitary Cells

Cloning, Expression and Regulation of Chicken Ovalbumin Upstream Promoter Transcription Factors (COUP-TFII and EAR-2) in the Rat Anterior Pituitary Gland

Association between GH receptor polymorphism (exon 3 deletion), serum IGF1, semen quality, and reproductive hormone levels in 838 healthy young men

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