Effect of GH administration on GH and IGF-I receptors in porcine skeletal muscle and liver in relation to plasma GH-binding protein

1997 ◽  
Vol 155 (1) ◽  
pp. 19-26 ◽  
Author(s):  
S Combes ◽  
I Louveau ◽  
M Bonneau
Keyword(s):  
Skeletal Muscle ◽  
Specific Binding ◽  
Binding Protein ◽  
Growing Pigs ◽  
Mrna Levels ◽  
Large White ◽  
Receptor Mrna ◽  
Igf I ◽  
Plasma Gh ◽  
And Control

The present study was undertaken to determine the effect of GH administration on GH and IGF-I receptors in skeletal muscle compared with liver in growing pigs. Plasma IGF-I and GH-binding protein (GHBP) levels were also determined. Twelve Large White pigs (castrated males) were treated daily with 100 micrograms pituitary porcine GH (pGH) per kg body weight or vehicle for 41 days intramuscularly. Relative to controls, pGH administration increased plasma IGF-I concentrations by 3.3-fold. Administration of pGH had no effect on plasma GHBP levels. In liver, 125I-labelled bovine GH (bGH)-specific binding (P < 0.05) and GH receptor (GHR) mRNA levels (P < 0.05) were higher in pGH-treated than in control pigs. In longissimus dorsi (LD), 125I-labelled bGH specific binding did not differ significantly between the two groups while GHR mRNA levels (P < 0.05) were lower in pGH-treated than in control pigs. Administration of pGH had no effect on 125I-labelled bGH-specific binding and GHR mRNA levels in trapezius (TR). 125I-Labelled IGF-I-specific binding in liver was unaffected by pGH administration. Similarly, in liver, LD and TR, IGF-I receptor mRNA levels were not different between pGH-treated and control animals. It can be concluded that (1) GH binding and IGF-I receptor mRNA are not affected by GH in skeletal muscle, (2) GH influences GHR in a tissue-specific manner and (3) hepatic GHR and GHBP levels are not co-regulated.

Ontogeny of GH receptor and GH-binding protein in the pig

1996 ◽  
Vol 148 (2) ◽  
pp. 249-255 ◽  
Author(s):  
S Schnoebelen-Combes ◽  
I Louveau ◽  
M-C Postel-Vinay ◽  
M Bonneau
Keyword(s):  
Skeletal Muscle ◽  
Specific Binding ◽  
Binding Protein ◽  
Muscle Growth ◽  
Developmental Expression ◽  
Large White ◽  
Gh Receptor ◽  
Age Related ◽  
Liver Membranes ◽  
Plasma Gh

Abstract The present study was undertaken to examine the developmental pattern of GH receptor (GHR) and GHR gene expression in skeletal muscle (longissimus dorsi and trapezius (TR)) and liver from the last third of gestation until 1 year of age in male Large White (LW) and Meishan (MS) pigs. Plasma GH-binding protein (GHBP) levels were also measured. 125I-Labelled bovine GH (bGH) specific binding (not determined in foetal TR) and GHR mRNA were detected in skeletal muscle from 75 days of gestation until the adult stage with no clear age-related changes. By contrast, 125I-labelled bGH specific binding and GHR mRNA were undetectable or barely detectable in foetal liver. After birth, 125I-labelled bGH specific binding (P<0·001) and GHR mRNA in liver increased with age. The level of bGH binding to liver membranes was higher in MS than in LW pigs at 1, 45, 80 and 120 days of age and did not differ between breeds at the other ages. Specific binding of 125I-labelled human GH (hGH) to plasma GHBP was easily detected as early as 75 days of gestation and increased with age (P<0·001). The level of hGH binding to plasma GHBP was higher in MS than in LW pigs at 1, 80 and 120 days of age. It can be concluded that (1) the developmental expression of the GHR is tissue-specific, (2) the presence of GHBP in foetuses despite the absence of GHR in liver suggests that other tissues such as skeletal muscle could contribute to the generation of GHBP and (3) the presence of GHR in skeletal muscle as early as 75 days of gestation suggests that GH may play a role in foetal muscle growth. Journal of Endocrinology (1996) 148, 249–255

Effect of high-protein feed supplements on concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in plasma and on the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams

1993 ◽  
Vol 138 (3) ◽  
pp. 421-427 ◽  
Author(s):  
I. J. Clarke ◽  
T. P. Fletcher ◽  
C. C. Pomares ◽  
J. H. G. Holmes ◽  
F. Dunshea ◽  
...  
Keyword(s):  
Binding Protein ◽  
Plasma Concentrations ◽  
High Protein ◽  
Mrna Levels ◽  
Igf I ◽  
Pituitary Glands ◽  
Igf Binding ◽  
Plasma Gh ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Three groups of mature rams were maintained on diets of hay, hay+2% lupin or hay+2% cowpea for 11 weeks. Serial blood samples were taken at 15-min intervals for 12 h for the determination of GH and IGF-I content by radioimmunoassay and for IGF-binding protein-3 (IGFBP-3) levels by Western blotting. The rams were killed after 77 days of supplementary feeding and their pituitary glands analysed for content of GH and GH mRNA. Mean plasma GH and baseline GH levels were significantly (P<0·01) decreased in the rams fed lupin and cowpea compared with controls fed hay and GH pulse amplitude was significantly (P<0·001) decreased in the group fed the cowpea diet. The frequency of GH pulses was not significantly altered by either treatment. Plasma concentrations of IGF-I were elevated in rams fed lupin (P<0·001) or cowpea (P<0·05). IGFBP-3 levels were not significantly (P>0·05) altered by either treatment. There were no significant differences in pituitary content of GH mRNA but pituitary content of GH was increased in rams fed lupin (P<0·05) and cowpea (P=0·07). In conclusion, a high-protein diet decreases plasma GH levels and increases IGF-I without changing plasma IGFBP-3 levels in rams. Thus ongoing synthesis of GH, as indicated by the mRNA levels, may cause a build up of GH stores in the pituitary gland. Journal of Endocrinology (1993) 138, 421–427

Differential regulation of tissue insulin-like growth factor-binding protein (IGFBP)-3, IGF-I and IGF type 1 receptor mRNA levels, and serum IGF-I and IGFBP concentrations by growth hormone and IGF-I

1997 ◽  
Vol 154 (2) ◽  
pp. 319-328 ◽  
Author(s):  
A B Lemmey ◽  
J Glassford ◽  
H C Flick-Smith ◽  
J M P Holly ◽  
J M Pell
Keyword(s):  
Binding Protein ◽  
Cell Types ◽  
Target Tissue ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Direct Function ◽  
Receptor Mrna ◽  
Igf I ◽  
Igfbp 3

Abstract The aims of this investigation were (1) to examine IGF-binding protein-3 (IGFBP-3) mRNA levels in candidate tissues which might be important sources for blood IGFBP-3 (liver and skin) and in a target tissue for IGF-I action (skeletal muscle), and (2) to examine the effects of a single dose (500 μg) of GH or IGF-I on IGFBP-3 message levels in these tissues since temporal responses (4, 8 and 24 h after the single subcutaneous dose of peptide to GH-deficient dwarf rats) would indicate which peptide is the primary modulator of IGFBP-3 synthesis. Circulating IGF-I and IGFBP-3 concentrations were significantly increased (P<0·05) by IGF-I and GH. GH treatment increased liver IGFBP-3 mRNA levels by 4 h (P<0·001 over the 24 h) whereas IGF-I had no effect. Similarly, GH, but not IGF-I, increased muscle IGFBP-3 mRNA levels (P<0·001 for the 24 h study period). However, both IGF-I and GH induced increases in skin IGFBP-3 mRNA abundance throughout the 24 h period (P<0·001 and P<0·01 respectively) and skin IGFBP-3 message abundance was greater that in the liver. Liver IGF-I mRNA levels were, as expected, increased after GH and tended to decrease after IGF-I treatment; muscle IGF-I mRNA was increased by GH (P<0·001) and, interestingly, progressively increased by IGF-I (P<0·05 for the 24 h period); skin IGF-I mRNA levels were unchanged by both peptides. The IGF-I induced increase in serum IGFBP-3 concentrations in the absence of an increase in hepatic IGFBP-3 mRNA levels and a paucity of liver IGF-I type 1 receptor mRNA imply that other sources of IGFBP-3 protein or synthesis must exist. The response of skin IGFBP-3 mRNA levels to both GH and IGF-I suggests that other cell types, such as fibroblast-derived cells, could be more important than the liver in the regulation of circulating reservoir IGFBP-3 in certain circumstances. In contrast to some current suggestions, the rapid and consistent GH-induced increase in IGFBP-3 message levels in all tissues studied implies that GH might have a direct function in the regulation of IGFBP-3 synthesis. Journal of Endocrinology (1997) 154, 319–328

scholarly journals The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses

2000 ◽  
Vol 166 (3) ◽  
pp. 565-577 ◽  
Author(s):  
LR Green ◽  
Y Kawagoe ◽  
DJ Hill ◽  
BS Richardson ◽  
VK Han
Keyword(s):  
Skeletal Muscle ◽  
Growth Factors ◽  
Umbilical Cord ◽  
Fetal Growth ◽  
Binding Proteins ◽  
Negative Impact ◽  
Mrna Levels ◽  
Igf I ◽  
Near Term ◽  
Insulin Like Growth Factors

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

Regulation of porcine insulin-like growth factor I and growth hormone receptor mRNA expression by energy status

1994 ◽  
Vol 266 (5) ◽  
pp. E776-E785 ◽  
Author(s):  
P. A. Weller ◽  
M. J. Dauncey ◽  
P. C. Bates ◽  
J. M. Brameld ◽  
P. J. Buttery ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Rates ◽  
Mrna Levels ◽  
Energy Status ◽  
Factor I ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Igf I ◽  
Class 1

Regulation of insulin-like growth factor I (IGF-I) and growth hormone (GH) receptor mRNA in liver and muscle by energy status was assessed in 2-mo-old pigs by altering thermoregulatory demand and energy intake over a 5-wk period to produce a range of plasma IGF-I concentrations from 3.5 +/- 0.7 to 28.9 +/- 6.2 nmol/l. These values were related directly to growth rates (0.06 +/- 0.02 to 0.44 +/- 0.01 kg/day) and total hepatic IGF-I mRNA levels. Increased growth rates were accompanied by an increase in hepatic class 1 and class 2 IGF-I mRNA levels and an increase in the ratio of class 2 to class 1 IGF-I mRNA in liver, suggesting a distinct role for class 2 expression in the endocrine growth response. High levels of class 1 transcripts and a virtual absence of class 2 transcripts characterized all muscle tissues examined, and there was no correlation with plasma IGF-I levels. This suggests that growth promotion in response to increased energy status is regulated via endocrine hepatic IGF-I rather than via a paracrine response. The levels of GH receptor mRNA were positively correlated with overall growth rate (P < 0.005) in liver and negatively correlated (P < 0.05) in muscle, indicating distinct tissue-specific effects of energy status.

Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state

1999 ◽  
Vol 276 (4) ◽  
pp. R1164-R1171 ◽  
Author(s):  
K. M. Kelley ◽  
T. R. Johnson ◽  
J. Ilan ◽  
R. W. Moskowitz
Keyword(s):  
Glucose Concentration ◽  
Northern Analysis ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Response System ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Igf Receptor

Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor (IGF)-I in chondrocytes has been reported in a number of disease states associated with impaired glucose metabolism. Primary rabbit chondrocytes were investigated for changes in their IGF response system [type-I IGF receptor and IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic response to IGF-I [as35S-labeled proteoglycan ([35S]PG) production] in media containing varying ambient glucose concentrations. Whereas basal [35S]PG synthetic rate was unaffected by glucose concentration, synthetic responsiveness to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a “diabetic” glucose concentration (25 mmol/l). IGFBP expression, as measured by Northern analysis of mRNA levels and Western ligand blotting of secreted protein levels, was not significantly altered in the different glucose media, nor were there any differences in the cell surface localization of IGFBPs as assessed by affinity cross-linking with 125I-labeled IGF-I, suggesting that IGFBPs do not induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose occurred with 25–50% reductions in steady-state levels of IGF type-I receptor mRNA and protein. A significant correlation between IGF receptor mRNA level and synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose concentrations, suggesting that the loss of responsiveness in reduced glucose is manifested at the level of transcription and/or receptor mRNA stability. In contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose concentrations occurred without changes in receptor mRNA and protein levels, suggesting that IGF-I resistance was due to post-ligand-binding receptor defects. It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate glucose levels may constitute an important pathogenic mechanism in degenerative cartilage disorders.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats

1994 ◽  
Vol 12 (2) ◽  
pp. 215-224 ◽  
Author(s):  
M Phillip ◽  
H Werner ◽  
T Palese ◽  
A A Kowarski ◽  
B Stannard ◽  
...  
Keyword(s):  
Young Patients ◽  
Experimental Models ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
Kidney Size ◽  
Local Synthesis ◽  
Receptor Mrna ◽  
Igf I ◽  
Renal Changes

ABSTRACT Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24–48 h after streptozotocin (STZ) administration, there was a decrease of ∼12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by ∼50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (∼2·5-fold (after 24 h) and ∼ 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the ∼ 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.

scholarly journals Insulin-like growth factor I stimulates degradation of an mRNA transcript encoding the 14 kDa ubiquitin-conjugating enzyme

1996 ◽  
Vol 319 (2) ◽  
pp. 455-461 ◽  
Author(s):  
Simon S WING ◽  
Nathalie BEDARD
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Binding Proteins ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Mrna Transcript ◽  
Factor I ◽  
Igf I ◽  
Ubiquitin Conjugating Enzyme ◽  
Growth Factor I

Upon fasting, the ubiquitin-dependent proteolytic system is activated in skeletal muscle in parallel with the increases in rates of proteolysis. Levels of mRNA encoding the 14 kDa ubiquitin-conjugating enzyme (E214k), which can catalyse the first irreversible reaction in this pathway, rise and fall in parallel with the rates of proteolysis [Wing and Banville (1994) Am. J. Physiol. 267, E39-E48], indicating that the conjugation of ubiquitin to proteins is a regulated step. To characterize the mechanisms of this regulation, we have examined the effects of insulin, insulin-like growth factor I (IGF-I) and des(1–3) insulin-like growth factor I (DES-IGF-I), which does not bind IGF-binding proteins, on E214k mRNA levels in L6 myotubes. Insulin suppressed levels of E214k mRNA with an IC50 of 4×10-9 M, but had no effects on mRNAs encoding polyubiquitin and proteasome subunits C2 and C8, which, like E214k, also increase in skeletal muscle upon fasting. Reduction of E214k mRNA levels was more sensitive to IGF-I with an IC50 of approx. 5×10-10 M. During the incubation of these cells for 12 h there was significant secretion of IGF-I-binding proteins into the medium. DES-IGF-I, which has markedly reduced affinity for these binding proteins, was found to potently reduce E214k mRNA levels with an IC50 of 3×10-11 M. DES-IGF-I did not alter rates of transcription of the E214k gene, but enhanced the rate of degradation of the 1.2 kb mRNA transcript. The half-life of the 1.2 kb transcript was approximately one-third that of the 1.8 kb transcript and can explain the more marked regulation of this transcript observed previously. This indicates that the additional 3´ non-coding sequence in the 1.8 kb transcript confers stability. These observations suggest that IGF-I is an important regulator of E214k expression and demonstrate, for the first time, stimulation of degradation of a specific mRNA transcript by this hormone, while overall RNA accumulates.

scholarly journals Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

2000 ◽  
Vol 167 (2) ◽  
pp. 295-303 ◽  
Author(s):  
JW van Neck ◽  
NF Dits ◽  
V Cingel ◽  
IA Hoppenbrouwers ◽  
SL Drop ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Gh Receptor ◽  
Igf I ◽  
Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

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