scholarly journals Effect of growth hormone administration on IGF binding protein-3 mRNA levels in porcine tissues

1999 ◽  
Vol 22 (3) ◽  
pp. 261-272 ◽  
Author(s):  
V Dunaiski ◽  
FR Dunshea ◽  
PE Walton ◽  
C Goddard
Keyword(s):  
Steady State ◽  
Binding Protein ◽  
Rnase Protection Assay ◽  
Mrna Levels ◽  
Short Term ◽  
Gh Treatment ◽  
Rnase Protection ◽  
Igf I ◽  
Class 1 ◽  
Igfbp 3

The effect of short-term GH treatment on steady-state insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in liver, kidney, longissimus dorsi muscle, stomach and jejunum was examined in pigs. Ten female crossbred pigs were allocated to either saline or GH (70 microg/kg/day) treatment by subcutaneous injection for 4 days. They were allowed to feed ad libitum, and were weighed daily. At the end of the treatment period, the pigs were slaughtered and samples of liver, kidney, skeletal muscle, stomach and jejunum were collected and total RNA was extracted. Steady-state levels of IGFBP-3 mRNA were quantified by RNase protection assay and were compared with the level of IGF-I class 1 and class 2 transcripts. IGFBP-3 mRNA increased in response to GH in both liver and kidney, but not in the other tissues sampled. Hepatic IGF-I mRNA responded to short-term GH treatment with a fourfold increase in IGF-I class 1 mRNA and an eightfold increase in IGF-I class 2 mRNA, which was liver specific. IGF-I class 1 mRNA was not responsive to GH treatment in other tissues. The short-term nature of this treatment suggests that the increase in hepatic IGFBP-3 and IGF-I transcripts is a relatively early response to treatment with GH, and that the increase in plasma concentrations of IGFBP-3 in response to GH are derived from the liver, the kidney, or both.

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

Differential expression and hormonal regulation of alternatively spliced IGF-I mRNA transcripts in salmon

1994 ◽  
Vol 12 (1) ◽  
pp. 25-37 ◽  
Author(s):  
S J Duguay ◽  
P Swanson ◽  
W W Dickhoff
Keyword(s):  
Hormonal Regulation ◽  
Coho Salmon ◽  
Juvenile Fish ◽  
Rnase Protection Assay ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Rnase Protection ◽  
Mrna Transcripts ◽  
Igf I ◽  
Alternatively Spliced

ABSTRACT Salmon have been shown to express alternatively spliced IGF-I mRNA transcripts coding for four different IGF-I prohormones. These transcripts, now designated Ea-1, Ea-2, Ea-3 and Ea-4, differ in size due to the inclusion of additional sequences in the E domain-coding region of the molecule. In this study, the tissue distribution and hormonal regulation of expression of alternatively spliced IGF-I mRNA transcripts were investigated in coho salmon. IGF-I mRNAs were detected by solution hybridization/RNase protection assay in all tissues examined. GH treatment significantly increased hepatic IGF-I mRNA content. Hepatic IGF-I mRNA levels were not influenced by prolactin or somatolactin. Heart, fat, brain, kidney, spleen and ovary IGF-I mRNA levels were not affected by GH, prolactin or somatolactin. Ea-1, Ea-3 and Ea-4 mRNA transcripts were detectable in the liver, and Ea-1 and Ea-3 levels increased dramatically in response to GH treatment, whereas the amount of Ea-4 mRNA was unchanged. Most non-hepatic tissues expressed only the Ea-4 transcript, and expression was not influenced by GH, prolactin or somatolactin. Ea-1 and Ea-3 transcripts were visible in gill samples from fish treated with GH. The ovaries of juvenile fish expressed Ea-1, Ea-2 and Ea-4. The amounts of these transcripts were not changed by gonadotrophin treatment. During smoltification of juvenile coho salmon, liver and gill IGF-I mRNA levels increased with increasing plasma GH and thyroxine concentrations. Muscle, brain and ovary IGF-I mRNA levels were unchanged during this period. These data suggest that the liver is a major site of IGF-I production in response to GH. Heart, fat, brain, kidney, spleen and ovary did not show increased IGF-I mRNA levels in response to GH treatment. GH and prolactin had inconsistent effects on muscle IGF-I mRNA levels. Somatolactin and a gonadotrophin preparation did not stimulate IGF-I expression in tissues of juvenile fish. Differences in tissue GH responsiveness can be partially explained by the expression of alternatively spliced IGF-I mRNAs. Of the four hepatic IGF-I mRNA transcripts, Ea-1 and Ea-3 are GH-responsive, while Ea-2 and Ea-4 are not. Most non-hepatic tissues express only the Ea-4 transcript, and IGF-I mRNA levels do not increase after GH treatment. The increased IGF-I mRNA levels observed in gill tissue during smoltification suggest that other factors, in addition to GH, may regulate IGF-I expression. These data are also consistent with the hypothesis that IGF-I may mediate the osmoregulatory functions of GH during sea water adaptation.

scholarly journals A cell cycle analysis of growth-related genes expressed during T lymphocyte maturation.

1990 ◽  
Vol 111 (6) ◽  
pp. 2693-2701 ◽  
Author(s):  
J N Feder ◽  
C J Guidos ◽  
B Kusler ◽  
C Carswell ◽  
D Lewis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Steady State ◽  
T Lymphocyte ◽  
Ribonucleotide Reductase ◽  
Cellular Proliferation ◽  
Rnase Protection Assay ◽  
Minor Component ◽  
Mrna Levels ◽  
Rnase Protection

Fetal liver or bone marrow-derived T lymphocyte precursors undergo extensive, developmentally regulated proliferation in response to inductive signals from the thymic microenvironment. We have used neonatal mouse thymocytes size-separated by centrifugal elutriation to study the cell cycle stage-specific expression of several genes associated with cell proliferation. These include genes involved in the biosynthesis of deoxyribonucleotide precursors, such as dihydrofolate reductase (DHFR), thymidylate synthase (TS), and the M1 and M2 subunits of ribonucleotide reductase, as well as c-myc, a cellular oncogene of unknown function. Using nuclear run-on assays, we observed that the transcription rates for these genes, with the exception of TS, are essentially invariant not only throughout the cell cycle in proliferating cells, but also in noncycling (G0) cells. The TS gene showed a transient increase in transcription rate in cells which bordered between a proliferating and nonproliferating status. Studies of an elutriated T cell line, S49.1, yielded similar results, indicating that the process of immortalization has not affected the transcriptional regulation of these genes. Analysis of steady-state mRNA levels using an RNase protection assay demonstrated that the levels of DHFR and TS mRNA accumulate as thymocytes progress through the cell cycle. In contrast, only the M2 subunit of ribonucleotide reductase showed cyclic regulation. Finally, in contrast to cultured cell models, we observed an abrupt fivefold increase in the steady-state level of c-myc mRNA in the transition from G1 to S-phase. We conclude from these studies that the transcriptional regulation of specific genes necessary for cellular proliferation is a minor component of the developmental modulation of the thymocyte cell cycle.

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.

scholarly journals Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice

2002 ◽  
Vol 283 (5) ◽  
pp. E937-E945 ◽  
Author(s):  
Josef V. Silha ◽  
Yaoting Gui ◽  
Liam J. Murphy
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Glucose Homeostasis ◽  
Binding Protein ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Igfbp 3

Glucose homeostasis was examined in male transgenic (Tg) mice that overexpressed the human insulin-like growth factor (IGF)-binding protein (IGFBP)-3 cDNA, driven by either the cytomegalovirus (CMV) or the phosphoglycerate kinase (PGK) promoter. The Tg mice of both lineages demonstrated increased serum levels of human (h) IGFBP-3 and total IGF-I compared with wild-type (Wt) mice. Fasting blood glucose levels were significantly elevated in 8-wk-old CMV-binding protein (CMVBP)-3- and PGK binding protein (PGKBP)-3-Tg mice compared with Wt mice: 6.35 ± 0.22 and 5.22 ± 0.39 vs. 3.99 ± 0.26 mmol/l, respectively. Plasma insulin was significantly elevated only in CMVBP-3-Tg mice. The responses to a glucose challenge were significantly increased in both Tg strains: area under the glucose curve = 1,824 ± 65 and 1,910 ± 115 vs. 1,590 ± 67 mmol · l−1 · min for CMVBP-3, PGKBP-3, and Wt mice, respectively. The hypoglycemic effects of insulin and IGF-I were significantly attenuated in Tg mice compared with Wt mice. There were no differences in adipose tissue resistin, retinoid X receptor-α, or peroxisome proliferator-activated receptor-γ mRNA levels between Tg and Wt mice. Uptake of 2-deoxyglucose was reduced in muscle and adipose tissue from Tg mice compared with Wt mice. These data demonstrate that overexpression of hIGFBP-3 results in fasting hyperglycemia, impaired glucose tolerance, and insulin resistance.

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

Corticosteroid receptor mRNA expression is unaffected by corticosteroids in rat kidney, heart, and colon

1996 ◽  
Vol 270 (5) ◽  
pp. C1343-C1353 ◽  
Author(s):  
B. Escoubet ◽  
C. Coureau ◽  
M. Blot-Chabaud ◽  
J. P. Bonvalet ◽  
N. Farman
Keyword(s):  
Steady State ◽  
Rat Kidney ◽  
Hormone Replacement ◽  
Mrna Level ◽  
Rnase Protection Assay ◽  
Distal Colon ◽  
Mrna Levels ◽  
Adult Rats ◽  
Rnase Protection ◽  
Steady State Levels

Hormones can regulate the expression of their own receptor. We have examined whether adrenalectomy (ADX) and hormone replacement by physiological doses of aldosterone or dexamethasone could modulate the expression of glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) at the mRNA level in the rat kidney, distal colon, and heart. Adult rats were adrenalectomized and received or did not receive an infusion of aldosterone (5 micrograms.100 g-1.day-1) or dexamethasone (10 micrograms.100 g-1.day-1). No significant change in steady-state levels of both MR and GR mRNA was detectable by using ribonuclease (RNase) protection assay (RPA) after either ADX or hormone replacement. Because the kidney is heterogeneous with regard to MR expression, RPA was adapted for measurements on microdissected nephron segments. GR mRNA is expressed at comparable levels all along the nephron, whereas MR mRNA is restricted to the distal nephron. No effect of ADX or GR and MR mRNA levels was detected in any nephron segment that was either aldosterone sensitive or insensitive. In situ hybridization confirmed the absence of corticosteroid-dependent modulation of MR mRNA in all kidney cell types. We conclude that variations of corticosteroid status do not affect MR and GR mRNA steady-state levels in heart, colon, and kidney and thus do not participate to the functional adaptations that are known to depend on hormonal status.

scholarly journals Testosterone effect on growth and growth mediators of the GH-IGF-I axis in the liver and epiphyseal growth plate of juvenile rats

1999 ◽  
Vol 23 (2) ◽  
pp. 209-221 ◽  
Author(s):  
A Zung ◽  
M Phillip ◽  
SA Chalew ◽  
T Palese ◽  
AA Kowarski ◽  
...  
Keyword(s):  
Mrna Abundance ◽  
Mrna Levels ◽  
Short Term ◽  
Term Study ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Long Term Study ◽  
Igf I ◽  
Igfbp 3

Several studies have suggested that testosterone may have a direct, GH-independent effect on growth. In order to assess possible mechanism(s) whereby testosterone exerts its growth-promoting effect, we evaluated its effect on growth mediators of the GH-IGF-I axis, in both the liver and the epiphyseal growth plate (EGP). Testosterone was administered to peripubertal rats and the responses of mRNA of GH receptor, IGF-I, IGF-I receptor and IGF-binding proteins-1 and -3 (IGFBP-1 and IGFBP-3) as well as circulating IGF-I were evaluated in two time-related models: over 12 h after a single injection (short-term study) and 10 days after continuous administration (long-term study). Rats in the short-term study were castrated and were killed 1, 4, 6 and 12 h post injection. Rats in the long-term study were divided into two groups: castrated vs castrated and hypophysectomized, in order to assess the effect of testosterone in the presence and absence of GH. mRNA levels were determined by RNase protection assay, and serum IGF-I by RIA. Testosterone enhanced weight gain in the rats treated for 10 days, a change that was similar in the presence or absence of GH. This effect was relatively small, however, by comparison with the total weight gained without testosterone. Testosterone had no effect on hepatic IGF-I mRNA abundance but induced a reduction in circulating IGF-I levels, in both the short- and long-term study. Testosterone had no effect on hepatic GH receptor and IGFBP-3 mRNA levels but resulted in a transient, short-term elevation in IGFBP-1 mRNA levels that was maximal 4 h post injection.In the EGP, neither testosterone administration nor hypophysectomy had any effect on IGF-I and IGF-I receptor mRNA levels. However, testosterone increased GH receptor mRNA abundance after 10 days of continuous administration in hypophysectomized rats only.These data suggest that the effect of testosterone on growth (as assessed by weight gain) is small and is not mediated by changes in hepatic gene expression of IGF-I, IGF-I receptor, IGFBP-1, IGFBP-3 or circulating IGF-I. At the EGP, the testosterone effect on linear growth is not mediated through changes in mRNA abundance of IGF-I and IGF-I receptor. The small but significant elevation of GH receptor mRNA levels in hypophysectomized rats may suggest a testosterone-mediated augmentation of a GH effect at the target organ.

scholarly journals Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

2008 ◽  
Vol 93 (7) ◽  
pp. 2819-2827 ◽  
Author(s):  
Jean L. Chan ◽  
Catherine J. Williams ◽  
Patricia Raciti ◽  
Jennifer Blakeman ◽  
Theodore Kelesidis ◽  
...  
Keyword(s):  
Binding Protein ◽  
Major Effect ◽  
Normal Weight ◽  
Energy Deficit ◽  
Short Term ◽  
Hypothalamic Amenorrhea ◽  
Igf System ◽  
Leptin Deficiency ◽  
Igf I ◽  
Igfbp 3

Abstract Context: States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. Objective: The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. Design, Setting, Patients, and Intervention: We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2–3 months of r-metHuLeptin treatment. Main Outcome Measures: GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. Results: During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. Conclusions: The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Serum growth hormone (GH) binding protein, IGF-I and IGFBP-3 in patients with β-thalassaemia major and the effect of GH treatment

1998 ◽  
Vol 48 (5) ◽  
pp. 641-646 ◽  
Author(s):  
L. C. K. Low ◽  
M. C. Postel-Vinay ◽  
E. Y. W. Kwan ◽  
P. T. Cheung
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Thalassaemia Major ◽  
Gh Treatment ◽  
Serum Growth Hormone ◽  
Igf I ◽  
Igfbp 3
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