scholarly journals Interactions between the ovary and the local IGF-I axis modulate mammary development in prepubertal heifers

2003 ◽  
Vol 177 (2) ◽  
pp. 295-304 ◽  
Author(s):  
SD Berry ◽  
RD Howard ◽  
PM Jobst ◽  
H Jiang ◽  
RM Akers
Keyword(s):  
Mrna Expression ◽  
Specific Binding ◽  
Mammary Development ◽  
Serum Concentrations ◽  
Fat Pad ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Local Expression ◽  
Igfbp 3

The objective was to determine the effects of ovariectomy and epithelial-stromal interactions on mammary development and local expression of IGF-I and IGF-binding protein (IGFBP) mRNA in prepubertal heifers. An epithelium-free ('cleared') fat pad (CFP) was prepared in two glands in each of 14 Holstein heifers, aged 1-3 Months. Eight of the calves were also ovariectomized. Serum concentrations of GH, IGF-I and prolactin were not affected by ovariectomy. At 6 Months of age, calves were killed to provide mammary samples of parenchyma, CFP and intact fat pad (MFP). Total mammary mass was reduced in ovariectomized calves (130+/-21 g vs 304+/- 25 g; P<0.001), and in several cases parenchymal tIssue was essentially absent. Uterus weight was also reduced by ovariectomy (14.5+/-3.8 g vs 30.4+/-4.5 g; P<0.05). In support of our hypothesis that local IGF-I mediates prepubertal mammary development, mRNA expression of IGF-I was lower in ovariectomized than in control calves (62.1+/-7.8 vs 91.6+/-7.8 arbitrary units; P<0.05). Specific binding of IGF-I to mammary parenchymal microsomes was also reduced by ovariectomy (377+/-142 vs 868+/-82 c.p.m.; P<0.01), suggesting decreased sensitivity to IGF-I. Expression of IGFBP-3 and IGFBP-5 mRNA were not influenced by ovariectomy. Expression of IGF-I, IGFBP-3 and IGFBP-5 mRNA did not differ between CFP and MFP, suggesting that expression of these factors was not influenced by interactions between stroma and developing epithelium. Overall, the data suggested that interactions between the ovary and the local IGF-I axis act to optimize the availability and effectiveness of IGF-I within the gland to stimulate mammary growth.

scholarly journals Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa
Keyword(s):  
Gene Expression ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Serum Concentrations ◽  
Gh Receptor ◽  
Its Gene ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

IGFBP mRNA expression in small intestine of rat during postnatal development

2001 ◽  
Vol 281 (6) ◽  
pp. G1378-G1384 ◽  
Author(s):  
C. A. Shoubridge ◽  
C.-B. Steeb ◽  
L. C. Read
Keyword(s):  
Mrna Expression ◽  
Postnatal Development ◽  
Age Groups ◽  
Rat Intestine ◽  
Age Related ◽  
Igf I ◽  
Igf Binding ◽  
Old Rats ◽  
Igf Binding Protein ◽  
Igfbp 3

In contrast to the adult gut, the immature intestine is refractory to subcutaneously infused insulin-like growth factor I (IGF-I). IGF binding protein (IGFBP) mRNA expression was characterized in intestinal tissues from 6-, 19-, and 90-day-old rats to determine if changes in local expression could account for this age-related change in IGF-I potency. For all age groups, IGFBP-3 to -6, but not IGFBP-1 or -2, were detected by Northern blot analysis. IGFBP-3, -4, and -5 were more intensely expressed in the 6-day-old rat intestine compared with weanling or adult tissue. In contrast, IGFBP-6 expression peaked at the time of weaning. In situ hybridization showed IGFBP-3 to -6 expression was confined to cells of the lamina propria and submucosa and also in the muscularis layer for IGFBP-5. Furthermore, the pattern of IGFBP-5 localization in the intestine changed with development. The findings indicate that the expression of IGFBP-3 to -6 is higher in the immature intestine compared with the adult intestine, suggesting locally produced IGFBPs may inhibit systemically derived IGF-I action in the intestine. Therefore, changes to local IGFBP expression may contribute to the varying response of the rat intestine to IGF-I peptides during postnatal development.

scholarly journals Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

2006 ◽  
Vol 188 (3) ◽  
pp. 503-511 ◽  
Author(s):  
M Granado ◽  
A I Martín ◽  
T Priego ◽  
M A Villanúa ◽  
A López-Calderón
Keyword(s):  
Gene Expression ◽  
Kupffer Cells ◽  
Inhibitory Effect ◽  
Gadolinium Chloride ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-α (TNF-α) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-α. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.

IGF-I and IGFBP-3 transport in the rat heart

2003 ◽  
Vol 284 (1) ◽  
pp. E237-E239 ◽  
Author(s):  
Mary Boes ◽  
Brian L. Dake ◽  
Barbara A. Booth ◽  
Alexander Sandra ◽  
Mathew Bateman ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rat Heart ◽  
Specific Binding ◽  
Beating Heart ◽  
Perfused Rat Heart ◽  
Igf I ◽  
Igf Binding ◽  
Plausible Mechanism ◽  
Igf Binding Protein ◽  
Igfbp 3

Specific binding of IGF-binding protein (IGFBP)-3 was shown to be present in the isolated, beating rat heart. The uptake of perfused 125I-labeled IGF-I in the beating heart was decreased to 9% by blocking IGF-I binding sites with the IGF-I analog Long R3 (LR3) IGF-I. When LR3 was perfused with complexes of125I-IGF-I · IGFBP-3, uptake of125I-IGF-I was decreased to 41%, which was significantly greater than LR3 and 125I-IGF-I (41 vs. 9%). These data suggest that both microvessel IGF-I and IGFBP-3 binding sites contribute to the transport of IGF-I in the perfused rat heart. This also suggests a novel and plausible mechanism whereby circulating IGFs reach sites of IGF bioactivity.

scholarly journals Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats

2003 ◽  
Vol 179 (1) ◽  
pp. 107-117 ◽  
Author(s):  
T Priego ◽  
M Granado ◽  
I Ibanez de Caceres ◽  
AI Martin ◽  
MA Villanua ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inhibitory Effect ◽  
Low Doses ◽  
Serum Concentrations ◽  
Its Gene ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Higher Doses ◽  
Igfbp 3

While it is well known that sepsis inhibits serum IGF-I and its gene expression in the liver, the effect on pituitary GH and IGF-binding protein-3 (IGFBP-3) is poorly understood. The GH-IGF-I-IGFBP-3 response to different doses of lipopolysaccharide (LPS) administration has been investigated in adult male rats. Two experiments were performed, administration of low doses of LPS (5, 10, 50 and 100 microg/kg) and high doses of LPS (100, 250, 500 and 1000 microg/kg). Rats received two i.p. injections of LPS (at 1730 h and 0830 h the following day) and were killed 4 h after the second injection. LPS administration induced a biphasic response in serum concentrations of GH, with an increase at the 10 microg/kg dose, followed by a decrease at higher doses (100 microg/kg on up). Pituitary GH mRNA was also increased by the administration of 10 and 50 microg/kg LPS, whereas at higher doses LPS did not modify pituitary GH mRNA. We also analyzed the GH response to LPS in primary pituitary cell cultures. When exposed to LPS, in the culture medium, there was an increase in GH release at the concentration of 0.1 and 10 ng/ml, whereas more concentrated LPS did not modify GH release. Serum concentrations of IGF-I declined in a dose-dependent fashion after LPS administration in the rats injected with 10 microg/kg LPS on up. This decrease is secondary to modifications in its synthesis in the liver, since endotoxin injection decreased both IGF-I and its mRNA in the liver. The liver GH receptor mRNA was also decreased by LPS administration, but only in the animals injected with high LPS doses. There was a decrease in both the IGFBP-3 serum levels and its gene expression in the liver with all LPS doses studied. These data suggest a biphasic LPS effect on pituitary GH, a stimulatory effect at low doses and an inhibitory effect at higher doses, whereas it has a clear inhibitory effect on IGF-I and IGFBP-3 synthesis in the liver. The decrease in liver IGFBP-3 mRNA and in serum concentrations of IGFBP-3 in the rats injected with LPS may contribute to the decrease in serum concentrations of IGF-I.

scholarly journals Effect of chronic thyroxine treatment on IGF-I, IGF-II and IGF-binding protein expression in mammary gland and liver during pregnancy and early lactation in rats

2002 ◽  
pp. 729-739 ◽  
Author(s):  
R Rosato ◽  
D Lindenbergh-Kortleve ◽  
J Neck ◽  
S Drop ◽  
G Jahn
Keyword(s):  
Mammary Gland ◽  
Binding Protein ◽  
Mammary Development ◽  
Mammary Tissue ◽  
Mrna Levels ◽  
Liver Growth ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

OBJECTIVE: Hyperthyroidism in rats produces organ hypertrophy and increases in circulating IGF-I and IGF-binding protein (IGFBP)-3. Chronic treatment with thyroxine (T(4)) during pregnancy advances parturition, blocks lactation and changes several hormone receptors in mammary gland and liver. Since IGFs are implicated in mammary and liver growth and in differentiation, we studied the effects of hyperthyroidism, induced by daily injections of T(4) (0.25 mg/kg). DESIGN AND METHODS: Using quantitative RT-PCR and in situ hybridization, the gene expression of IGF-I, IGF-II and the IGFBPs was determined in mammary gland and liver of rats at estrus and days 7, 14 and 21 of pregnancy (G7, G14, G21), day 1 postpartum (L1) and 3 days after removing the litter (L4). Circulating levels of IGF-I, tri-iodothyronine (T(3)), PRL and GH were measured. RESULTS: T(4) treatment (HT) increased circulating T(3) save on G21, did not change serum IGF-I, increased PRL on G21 and decreased GH on L1. PRL decreased on L1 because of the absence of lactation. Hepatic IGF-I mRNA was low during pregnancy and increased on L4. HT advanced this increase to L1. In controls, liver IGFBP-3 mRNA levels decreased from G14 to G21, whereas IGFBP-4 showed an inverse pattern. HT lowered IGFBP-3 mRNA and increased IGFBP-4. Increases in mammary concentrations of IGF-I, IGFBP-3 and IGFBP-4 mRNAs were seen on G21. HT delayed these peaks to L1. Mammary IGF-II and IGFBP-2 mRNA levels were high on G7 and G14, and fell afterwards, with HT having no effects. IGFBP-5 mRNA decreased during pregnancy and increased on L1. HT increased IGFBP-5 levels in early pregnancy and on L1. IGF-I mRNA localized to connective and epithelial mammary tissue, while IGFBP-2 and IGFBP-5 mRNA was only in epithelial cells. CONCLUSION: These results imply a role for IGF-I, IGFBP-3 and IGFBP-4 in terminal mammary development, while IGF-II and IGFBP-2 may be implicated in early growth. IGFBP-5 has been implicated in mammary apoptosis, and the HT-induced increase may play a role in the premature mammary involution of the HT rats.

IGF-I and IGF-binding protein-3 in plasma of GH-deficient rats

1996 ◽  
Vol 150 (1) ◽  
pp. 67-76 ◽  
Author(s):  
A A Butler ◽  
B W Gallaher ◽  
G R Ambler ◽  
P D Gluckman ◽  
B H Breier
Keyword(s):  
Mrna Expression ◽  
Ternary Complex ◽  
Insulin Treatment ◽  
Binding Protein ◽  
Saline Control ◽  
Treatment Groups ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Abstract The majority of IGF-I circulates in a large (150 kDa) ternary complex with IGF-binding protein-3 (IGFBP-3) and a non-IGF-binding acid-labile subunit. The secretion of ternary complex into the circulation from liver has been considered to be GH-dependent; however, recent data indicate that GH does not directly regulate hepatic IGFBP-3 synthesis. To examine the role of insulin in regulating plasma IGFBP-3 levels, postpubertal male GH-deficient (dw/dw) rats were treated every 8 h with injections (s.c.) of 0·9% saline, 20 μg insulin/day, 200 μg hIGF-I/day, or 20 μg insulin/day plus 200 μg hIGF-I/day, for 10 days with the animals being killed 2–3 h after the final injection. Hypoglycaemia was not observed in any of the treatment groups. hIGF-I treatment increased longitudinal growth and weight gain (P<0·05), while insulin treatment had no effect. Plasma IGF-I levels were increased in groups treated with hIGF-I (P<0·05), while insulin treatment resulted in a reduction (P<0-05): saline=267·1 ± 15·6 (ng/ml ± s.e.m.), insulin=219·3 ± 17·5, hIGF-I=391·7 ± 17·6, insulin plus hIGF-I=357·5 ± 31·8. Hepatic IGF-I mRNA expression was increased in insulin-treated dw/dw rats in comparison with hIGF-I-treated animals (P<0·05) but not in comparison with saline control or the combined treatment groups. Plasma levels of intact IGFBP-3, measured by ligand blot analysis, were increased in all treatment groups compared with saline (P<0·05): saline=100·0 ± 9·4% (% of saline ± s.e.m.), insulin=149·9 ± 17·5%, hIGF-I= 191·4 ± 17·3%, insulin plus hIGF-I=205·4 ± 15·3%. The levels of the 28/32 kDa IGFBPs and IGFBP-4 in plasma were increased by hIGF-I treatment (P<0·05) but not by insulin treatment. Hepatic specific 125I-bovine GH binding was not significantly different in any of the treatment groups. This study provides the first evidence in non-diabetic animals that insulin regulates hepatic IGF-I mRNA expression, plasma IGF-I and plasma IGFBP-3 levels in the GH-deficient state without changes in hepatic GH receptors. The divergent response of plasma IGF-I and IGFBP-3 levels to insulin treatment in the present study may indicate an effect of insulin on the clearance of IGF-I from the circulation. Journal of Endocrinology (1996) 150, 67–76

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Effects of decreased estradiol-17β on the serum and anterior pituitary IGF-I system in pigs

2005 ◽  
Vol 187 (3) ◽  
pp. 369-378 ◽  
Author(s):  
C K Hilleson-Gayne ◽  
J A Clapper
Keyword(s):  
Anterior Pituitary ◽  
Percentage Increase ◽  
Serum Concentrations ◽  
Blood Samples ◽  
Treatment Groups ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Estradiol 17Β

To further delineate the role of estradiol in the IGF system an experiment was conducted to determine the dosage of the aromatase inhibitor, anastrozole, needed to decreases serum concentrations of estradiol-17β (E2) in maturing boars. A second experiment was conducted to determine if administration of anastrozole to growing boars decreased serum concentrations of E2 and affected components of the serum and anterior pituitary gland (AP) IGF system vs untreated boars and barrows. In Experiment 1, 12 crossbred boars (292 days, 158 kg) were administered either 0, 1 or 10 mg/day anastrozole (n=4/group) beginning on day 1. Blood samples were collected every 7–14 days. Mean serum concentrations of E2 were decreased (P < 0·05) in the 10 mg group vs the 0 and 1 mg groups by day 36; however, no difference (P > 0·05) existed between the 0 and 1 mg groups. In Experiment 2, 24 crossbred boars and 12 barrows (101 days, 44 kg) were stratified by litter to one of three treatment groups (n=12): boars administered 10 mg/day anastrozole, boars administered 0 mg/day, and barrows administered 0 mg/day. Blood samples were collected and pigs were weighed on day 0 and every 14 days thereafter, then killed on day 84 when blood and APs were collected. The 10 mg/day pigs were fed the anastrozole-amended diet beginning on day 1. Mean serum concentrations of E2 did not differ (P > 0·05) between the 10 mg/day pigs and 0 mg/day pigs on day 0; however, on day 15 through to 84 mean serum concentrations of E2 were greater (P < 0·05) in 0 mg/day pigs than in the 10 mg/day pigs. Mean percentage increase in serum concentrations of IGF-I was greater (P < 0·05) in untreated boars than anastrozole-treated boars and barrows from day 58 through to 84. Mean percentage of basal IGF-I increased (P < 0·05) from day 29 through to 84 in untreated boars. Mean relative amounts of AP IGF-binding protein (IGFBP)-2 and -5 were less (P < 0·01) in 10 mg/day pigs than in the 0 mg/day pigs, but each was greater (P < 0·01) than in barrows administered 0 mg/day. These results indicate anastrozole administered at a dosage of 10 mg/day suppresses serum concentrations of E2 in pigs. Administration of anastrozole to boars reduced the percentage increase in serum concentrations of IGF-I and relative amounts of AP IGFBP-2 and -5. These data further support a role for E2 in regulating components of the IGF system in pigs.

Sign in / Sign up

Export Citation Format

Share Document