Somatostatin regulates hepatic growth hormone sensitivity by internalizing growth hormone receptors and by decreasing transcription of growth hormone receptor mRNAs

2007 ◽  
Vol 292 (5) ◽  
pp. R1956-R1962 ◽  
Author(s):  
Nicole M. Very ◽  
Mark A. Sheridan
Keyword(s):  
Growth Hormone ◽  
Steady State ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Binding Capacity ◽  
Isolated Hepatocytes ◽  
Receptor Internalization ◽  
Dependent Manner ◽  
Growth Hormone Receptors ◽  
Steady State Levels

Somatostatins (SSs), a diverse family of peptide hormones, have been shown to inhibit the release of growth hormone (GH) from the pituitary. In this study, we used rainbow trout to determine whether or not SSs affect growth in an extrapituitary manner, in particular, by decreasing GH sensitivity in liver. SS-14 significantly decreased hepatic GH binding in fish implanted (5.8 × 10−11 mol/h) for 15 days and in isolated hepatocytes. The processing of 125I-labeled trout GH (tGH) by isolated hepatocytes was investigated to determine whether or not the decrease in GH binding capacity resulted from receptor internalization. The internalization of 125I-labeled tGH was time dependent. By 6 h, 100 ng/ml SS-14 increased internalization of 125I-labeled tGH 58% over that observed in controls. Steady-state levels of mRNAs encoding the two hepatic growth hormone receptors (GHRs) of trout, GHR 1 and GHR 2, were measured to determine whether or not decreased GH binding capacity also resulted from decreased GHR synthesis. SS-14 directly inhibited steady-state levels of GHR 1 and GHR 2 mRNA in isolated hepatocytes in a concentration-dependent manner. The inhibitory effects of SS-14 on steady-state levels of GHR mRNAs resulted from reduced GHR mRNA transcription and not from altered mRNA stability. These results indicate that SSs regulate hepatic GH sensitivity by increasing GHR internalization and by altering GHR expression and suggest that SSs coordinate growth at the level of the pituitary, as well as at extrapituitary levels.

scholarly journals Phosphorylation of Highly Purified Growth Hormone Receptors by a Growth Hormone Receptor-associated Tyrosine Kinase

1989 ◽  
Vol 264 (31) ◽  
pp. 18654-18661
Author(s):  
C Carter-Su ◽  
J R Stubbart ◽  
X Y Wang ◽  
S E Stred ◽  
L S Argetsinger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Tyrosine Kinase ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Growth Hormone Receptors

The interrelationship between and the regulation of hepatic growth hormone receptors and circulating GH binding protein in the pig

1992 ◽  
Vol 126 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Geoffrey R Ambler ◽  
Bernhard H Breier ◽  
Andrzej Surus ◽  
Hugh T Blair ◽  
Stuart N McCutcheon ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Binding Capacity ◽  
Binding Protein ◽  
Somatic Growth ◽  
Gh Receptor ◽  
Age Related ◽  
Igf I ◽  
Serum Gh

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.

scholarly journals Activation of Chimeric and Full-length Growth Hormone Receptors by Growth Hormone Receptor Monoclonal Antibodies

1998 ◽  
Vol 273 (9) ◽  
pp. 5307-5314 ◽  
Author(s):  
Scott W. Rowlinson ◽  
Stuart N. Behncken ◽  
Jennifer E. Rowland ◽  
Richard W. Clarkson ◽  
Christian J. Strasburger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Monoclonal Antibodies ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Full Length ◽  
Length Growth ◽  
Growth Hormone Receptors

scholarly journals Ontogeny of growth hormone receptor gene expression in tissue of growth-selected strains of broiler chickens

1998 ◽  
Vol 156 (1) ◽  
pp. 67-75 ◽  
Author(s):  
JN Mao ◽  
J Burnside ◽  
MC Postel-Vinay ◽  
JD Pesek ◽  
LA Cogburn ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Steady State ◽  
Broiler Chickens ◽  
Growth Hormone Receptor ◽  
Abdominal Fat ◽  
Mrna Levels ◽  
Steady State Levels ◽  
Different Populations ◽  
Leg Muscle ◽  
Plasma Gh

The purpose of this study was to determine the relationship between genetic selection for growth traits and tissue expression of the chicken growth hormone receptor (cGHR) gene. Two different populations of broiler chickens were studied. One population consisted of strain (S) 80, selected for 14 generations for high 9-week body weight (BW), and its progenitor, S90 (a 1950's strain). The second population consisted of S21, selected for 10 generations for high 4-week BW and low abdominal fat, and its progenitor S20 (a 1970's strain). Tissue (liver, fat, breast and leg muscle) and blood samples were collected from six birds/strain at 2-week intervals between 1 and 11 weeks of age. An RNase protection assay was developed to measure mRNA levels of full-length cGHR (3.2 and 4.3 kb) transcripts and chicken glyceraldehyde 3-phosphate dehydrogenase (for normalization) in total RNA prepared from tissue. Analysis of the area-under-curve (AUC) was used for strain comparisons of certain developmental profiles (BW, plasma hormones and tissue cGHR mRNA). The BW AUC showed that the growth rates are different (P < 0.05) among the four strains (S21 > S20 > S80 > S90). Both slow-growing strains (S90 and S80) had a higher (P < 0.05) plasma GH AUC than the two fast-growing strains (S20 and S21). The plasma T3 AUC was highest (P < 0.05) in S90 due to maintenance of higher T3 levels after 3 weeks of age. At 11 weeks of age, hepatic and plasma GH-binding activities were positively related to growth rate (S21 > S20 > S80 > S90). However, the developmental increase in cGHR mRNA in liver and fat was similar among these different populations of growth-selected broiler chickens. Steady-state levels of cGHR mRNA increased in a developmental manner in the liver (5-fold at 9 weeks of age) and abdominal fat (4.5-fold at 11 weeks of age) of all strains. In contrast, there was no developmental increase or strain difference in cGHR mRNA levels in breast and leg muscle. There is a discrepancy between GH-binding activity in liver and plasma, which is different among strains, and steady-state levels of tissue cGHR mRNA which are similar among strains. These observations suggest that the cGHR is under translational or post-translational regulation which would determine the amount of cGHR protein available for GH binding.

scholarly journals Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

2006 ◽  
Vol 85 (5) ◽  
pp. 452-456 ◽  
Author(s):  
M.M. Zavarella ◽  
O. Gbemi ◽  
J.D. Walters
Keyword(s):  
Steady State ◽  
Connective Tissue ◽  
Inflammatory Mediator ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Temperature Dependent ◽  
Tnf Α ◽  
Steady State Levels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 μg/mL and a Vmax of 1.42 ng/min/μg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-α. In humans, systemically administered naproxen attained steady-state levels of 61.9 μg/mL in blood and 9.4 μg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 μg/mL and 1.5 μg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

The Ontogeny of Growth Hormone Receptors in the Rabbit Tibia*

Endocrinology ◽  
1988 ◽  
Vol 122 (6) ◽  
pp. 2562-2569 ◽  
Author(s):  
ROSS BARNARD ◽  
K. M. HAYNES ◽  
G. A. WERTHER ◽  
MICHAEL J. WATERS
Keyword(s):  
Growth Hormone ◽  
Hormone Receptors ◽  
Growth Hormone Receptors ◽  
Rabbit Tibia

Transduction pathways of GH in ovine mammary acini involving regulated and functional growth hormone receptors

2005 ◽  
Vol 23 (1) ◽  
pp. 55-66 ◽  
Author(s):  
E. Ying Chun ◽  
Lucette Belair ◽  
Genevieve Jolivet ◽  
Jean Djiane ◽  
Hélène Jammes
Keyword(s):  
Growth Hormone ◽  
Hormone Receptors ◽  
Growth Hormone Receptors
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