Human Liver Growth Hormone Receptor and Plasma Binding Protein: Characterization and Partial Purification*

Hocquette, Jean-Franqois; Postel-Vinay, Marie-Catherine; Djiane, Jean; Tar, Attila; Kelly, Paul A.

doi:10.1210/endo-127-4-1665

Cited by 50 publications

(21 citation statements)

References 25 publications

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“…albeit at low levels but was similar to that reported for hepatoma cell lines (Hep3B and HuH-7) and human liver (Hocquette et al 1990, Esposito et al 1994. Although the levels were insufficient for quantification by Scatchard analysis, comparison with the binding levels of several clones stably expressing GHR, suggests that the parental cell line expressed less than 1000 receptors per cell.…”

Section: Discussionsupporting

confidence: 88%

Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone

Laue

Finidori²,

Maamra³

et al. 2000

Journal of Endocrinology

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The interaction of GH, interleukin (IL)-6 and glucocorticoids is likely to be important in regulating the GHinsulin-like growth factor (IGF)-I axis. The signalling cascades activated by GH and IL-6 appear to be very similar, as demonstrated by studies using overexpression of the receptor and other components of the Jak-Stat and mitogen-activated protein (MAP) kinase pathways. Here we show that the human embryonic kidney cell line 293 (HEK293) expresses GH and IL-6 receptors endogenously. To determine which specific pathways might be activated by the two cytokines, at physiological levels of all components, we studied GH and IL-6 mediated signal transduction both under basal conditions and in the presence of overexpressed receptors and Stat proteins. Our results suggest a receptor specificity of Jak2 for GH receptors, and Jak1 for IL-6 receptors. Stat activation in response to GH and IL-6 was determined by reporter gene induction. Both GH and IL-6 were able to induce the reporter gene containing the Stat5 responsive element (LHRE) but the IL-6 response appeared to be mediated mainly through Stat3 activation. In contrast, the reporter gene containing the Stat3 responsive element (SIE) was IL-6 specific. The levels of gene induction by GH and IL-6 were not altered by the co-stimulation with GH and IL-6, suggesting that there is little cross-talk at the Jak-Stat activation level between the two cytokines. Neither GH nor IL-6 activated the MAP-kinase responsive serum response element (SRE), unless GH receptors or gp130 were overexpressed. Transfection of Stat3 or Stat5 expression vectors enhanced the response to GH and IL-6. Stimulation with dexamethasone synergistically enhanced GH activation of the LHRE reporter gene but had no effect on the IL-6 activation of the same reporter or on the SIE reporter gene. Thus, our studies suggest that while each cytokine, GH and IL-6, may activate various members of the Jak-Stat pathway in overexpression studies, specific activation of Stat3 by IL-6 and of Jak2 and Stat5 by GH can be observed in HEK293 cells and that in this system the synergistic effect of dexamethasone appears specific for Stat5.

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Section: Discussionsupporting

confidence: 88%

Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone

Laue

Finidori²,

Maamra³

et al. 2000

Journal of Endocrinology

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“…In the present study, DTT or -mercaptoethanol treatment resulted in the reduction of the M r of the serum GHBP complexes in all species, suggesting that the large bands observed by ligand blotting contain disulfide bonds. Similar results have been reported for human serum GHBP (Hocquette et al 1990).…”

Section: Discussionsupporting

confidence: 91%

“…Ligand blotting of GHBPs from goldfish, rabbit and rat sera was performed using a slight modification of published methods (Hocquette et al 1990, Vasilatos-Younken et al 1991. Briefly, 20 µg serum protein was separated by SDS-PAGE on a 7·5% gel under both reducing and nonreducing conditions (Laemmli 1970).…”

Section: Ligand Blotting Of Serum Ghbpmentioning

confidence: 99%

Identification of serum GH-binding proteins in the goldfish (Carassius auratus) and comparison with mammalian GH-binding proteins

Zhang

Marchant²

1999

Journal of Endocrinology

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The present study constitutes the characterization of a specific, high-affinity GH-binding protein (GHBP) in the serum of a teleost, the goldfish (Carassius auratus). GH-binding assay and ligand blotting techniques were employed to identify GHBPs in goldfish serum and hepatocyte culture medium. The binding characteristics and apparent molecular weights (M r ) of goldfish GHBPs were also compared with those of rabbit and rat. LIGAND analysis identified a single class of high-affinity and lowcapacity binding sites for iodinated recombinant carp GH (rcGH) in the goldfish serum, with an association constant (K a ) of 20·1 10 9 M 1 and a maximum binding capacity (B max ) of 161 fmol ml 1 serum. A single class of binding sites for iodinated recombinant sea bream GH and bovine GH (bGH) was also found in goldfish serum, but with a much lower affinity than that of rcGH. The binding affinity for iodinated bGH in rabbit and rat sera was found to be similar to that reported previously. Ligand blotting revealed multiple forms of GHBPs in sera of goldfish, rabbit and rat with M r ranging from 70 kDa to 400 kDa and 27 kDa to 240 kDa under non-reducing and reducing conditions respectively. A prominent band with M r of 66 kDa and a minor band with M r of 27 kDa were observed to occur in sera from all three species under reducing conditions. Iodoacetamide promoted the shedding of three GHBPs with M r of 25, 40 and 45 kDa from the cultured goldfish hepatocytes. The appearance of all bands was completely inhibited by the presence of excess unlabeled rcGH. Our results provide clear evidence that a GHBP exists in the goldfish and indicate that more information on teleost GHBPs is needed if the physiology of growth in teleosts is to be fully understood.

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“…A specific GH-BP with high binding affinity and low binding capacity has recently been described in human and animal serum (1)(2)(3)(4). Immunologic and biochemical studies have shown that this GH-BP is identical to the extracellular domain of the liver membrane GH receptor (5)(6)(7)(8). Studies of the GH-BP in rats revealed a quantitative relationship between the binding of GH to the circulating GH-BP and to the hepatic somatogenic receptor (9,10).…”

mentioning

confidence: 99%

Serum Growth Hormone-Binding Proteins in the Human Fetus and Infant

Massa

Zegher

Vanderschueren-Lodeweyckx

1992

Pediatr Res

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ABSTRACT. Growth hormone-binding protein (GH-BP) levels were studied in cord serum of 69 human infants born after 24 to 41 wk of gestation and in serum of 14 infants aged 1 to 3 mo. GH-BP levels were measured by HPLCgel filtration of serum incubated overnight with '251-hGH. The radioactive elution profile revealed two small I2'IhGH peaks of high molecular weight and a large peak, corresponding to monomeric Iz5I-hGH. The first peak of high molecular weight was variable, showed some of the characteristics (high molecular weight, displaceability by a large excess of unlabeled hGH) of the described low affinity, high capacity GH-BP, and did not correlate with gestational age or birth weight (peak I-BP). The second peak was identified as '251-hGH bound to the high affinity, low capacity GH-BP (peak 11-BP). Mean 2 SD specific binding of Iz5I-hGH to this peak was significantly (p < 0.0001) different between preterm infants (3.1 2 1.1%; n = 51), term infants at birth (4.2 f 1.1%; n = 18), and 1-to 3-mo-old infants (8.5 + 1.6%; n = 14). To evaluate the effect of intrauterine nutritional state, the ponderal index (weight/length3) was calculated. Peak 11-BP levels were lower (p < 0.05) in infants with the ponderal index < 2.35 (2.8 k 1.0%; n = 20) than in those with the ponderal index between 2.35 and 2.65 (3.4 k 1.2%; n = 29) or > 2.65 (3.8 2 1.2%; n = 20). We conclude that GH-BP are present in human cord serum throughout the 3rd trimester of gestation. The levels of peak 11-BP are influenced by fetal age and intrauterine growth and increase quickly after birth. (Pediatr Res 32: 69-72,1992)

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Human Liver Growth Hormone Receptor and Plasma Binding Protein: Characterization and Partial Purification*

Cited by 50 publications

References 25 publications

Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone

Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone

Identification of serum GH-binding proteins in the goldfish (Carassius auratus) and comparison with mammalian GH-binding proteins

Serum Growth Hormone-Binding Proteins in the Human Fetus and Infant

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