Regulation of serum insulin-like growth factor-I (IGF-I), hepatic growth hormone binding and IGF-I gene expression in the rat during pregnancy and lactation

1993 ◽  
Vol 139 (1) ◽  
pp. 89-95 ◽  
Author(s):  
M. T. Travers ◽  
R. J. Madon ◽  
D. J. Flint
Keyword(s):  
Gene Expression ◽  
Late Pregnancy ◽  
Liver Weight ◽  
Steady Increase ◽  
Early Lactation ◽  
Rna Content ◽  
Igf I ◽  
Pregnancy And Lactation ◽  
I Gene ◽  
Gh Resistance

ABSTRACT An apparent GH resistance occurs in pregnancy, since GH concentrations in serum are reported to be normal or elevated, whereas serum IGF-I falls to very low levels. To determine whether this GH resistance is manifest at the level of the hepatic GH receptor or in the ability of GH to initiate IGF-I gene expression, we have determined hepatic IGF-I mRNA expression, circulating IGF-I and hepatic GH binding during various stages of pregnancy and lactation in the rat. The concentration of IGF-I in serum fell from 37 ± 5 nmol/l (means ± s.e.m.) in virgin rats to 17 ± 1 nmol/l in rats in late pregnancy, recovered in early lactation (31 ± 3 nmol/l) but was again significantly lower than in virgin animals by mid-lactation (22 ± 3 nmol/l). Hepatic GH binding did not vary significantly during pregnancy but showed a small significant decrease in early lactation when expressed per mg membrane protein. When expressed as GH binding per liver, however, there were no significant changes in GH binding at any stage. Liver weight increased significantly between virgin and early pregnant animals (7·1 ± 0·2 g compared with 9·2 ± 0·5 g respectively, P<0·01) and continued to increase up to late lactation (14·3 ± 0·4 g). Similarly, although the amount of IGF-I gene expression/unit RNA declined in late pregnant when compared with virgin animals (6·0 ± 0·6 versus 3·4 ± 0·4 arbitrary optical density units respectively, P<0·05), when the increase in liver weight and RNA content during pregnancy was taken into account there was actually a steady increase in IGF-I gene expression per total liver throughout both pregnancy and lactation, the difference becoming significant by mid-lactation (P<0·05). Thus, when the changes in liver weight which take place during pregnancy and lactation are taken into account we conclude that any hepatic resistance to GH in late pregnancy and lactation must be a post-receptor event which is mitigated in large part by increase in liver size, cell number and RNA content. Journal of Endocrinology (1993) 139, 89–95

scholarly journals The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

2001 ◽  
pp. 529-534 ◽  
Author(s):  
A Lopez-Calderon ◽  
I Ibanez de Caceres ◽  
L Soto ◽  
T Priego ◽  
AI Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight Gain ◽  
Chronic Arthritis ◽  
Mrna Levels ◽  
Gh Receptor ◽  
Igf I ◽  
Male Wistar Rats ◽  
Design And Methods ◽  
I Gene ◽  
Gh Resistance

OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS- than in saline-treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.

scholarly journals Lack of Dietary Carbohydrates Induces Hepatic Growth Hormone (GH) Resistance in Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1948-1960 ◽  
Author(s):  
Maximilian Bielohuby ◽  
Mandy Sawitzky ◽  
Barbara J. M. Stoehr ◽  
Peggy Stock ◽  
Dominik Menhofer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Janus Kinase ◽  
Gh Secretion ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
I Gene ◽  
Gh Resistance

GH is a well established regulator of growth, lipid, and glucose metabolism and therefore important for fuel utilization. However, little is known about the effects of macronutrients on the GH/IGF system. We used low-carbohydrate/high-fat diets (LC-HFD) as a model to study the impact of fat, protein, and carbohydrates on the GH/IGF-axis; 12-wk-old Wistar rats were fed either regular chow, a moderate, protein-matched LC-HFD, or a ketogenic LC-HFD (percentage of fat/protein/carbohydrates: chow, 16.7/19/64.3; LC-HF-1, 78.7/19.1/2.2; LC-HF-2, 92.8/5.5/1.7). After 4 wk, body and tibia length, lean body mass, and fat pad weights were measured. Furthermore, we investigated the effects of LC-HFD on 1) secretion of GH and GH-dependent factors, 2) expression and signaling of components of the GH/IGF system in liver and muscle, and 3) hypothalamic and pituitary regulation of GH release. Serum concentrations of IGF-I, IGF binding protein-1, and IGF binding protein-3 were lower with LC-HF-1 and LC-HF-2 (P &lt; 0.01). Both LC-HFD-reduced hepatic GH receptor mRNA and protein expression, decreased basal levels of total and phosphorylated Janus kinase/signal transducers and activators of transcription signaling proteins and reduced hepatic IGF-I gene expression. Hypothalamic somatostatin expression was reduced only with LC-HF-1, leading to increased pituitary GH secretion, higher IGF-I gene expression, and activation of IGF-dependent signaling pathways in skeletal muscle. In contrast, despite severely reduced IGF-I concentrations, GH secretion did not increase with LC-HF-2 diet. In conclusion, lack of carbohydrates in LC-HFD induces hepatic GH resistance. Furthermore, central feedback mechanisms of the GH/IGF system are impaired with extreme, ketogenic LC-HFD.

Regulation of insulin-like growth factor-I gene expression by growth factors in cultured vascular smooth muscle cells

1990 ◽  
Vol 125 (3) ◽  
pp. 381-386 ◽  
Author(s):  
K. E. Bornfeldt ◽  
H. J. Arnqvist ◽  
G. Norstedt
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Basic Fgf ◽  
Aortic Smooth Muscle ◽  
Factor I ◽  
Igf I ◽  
I Gene

ABSTRACT The aim of this investigation was to study the regulation of insulin-like growth factor-I (IGF-I) gene expression in cultured rat aortic smooth muscle cells. Near-confluent cells were deprived of serum for 24 h and then exposed to IGF-I, insulin, serum, basic fibroblast growth factor (basic FGF), platelet-derived growth factor (PDGF-BB; consisting of B-chain homodimer) or GH for 24 h. Levels of IGF-I mRNA were measured by solution hybridization. The level of IGF-I mRNA was markedly decreased by 10% (v/v) newborn calf serum (78 ± 4 (s.e.m.) % decrease), 1 nmol basic FGF/1 (53 ± 8%), and 1 nmol PDGF-BB/1 (40 ± 3%) when measured after 24 h. The effect of PDGF-BB was significant after 6 h and became more marked after 24 h. GH (1 nmol/l or 0.1 μmol/l or insulin (1 nmol/l had no effect after 24 h, whereas IGF-I (1 nmol/l and insulin (10 μmol/l increased IGF-I mRNA 64 ± 20% and 46±14% respectively. The increase caused by IGF-I was demonstrated after 3 h, and was most marked after 24 h. Using Northern blot analysis of cultured aortic smooth muscle cells, IGF-I transcripts of 7-4, 1.7 and 1.1–0.8 kilobases were observed. Exposure of the cells to 10% serum, 1 nmol basic FGF/1 or 1 nmol PDGF-BB/1 for 48 h increased the cell number by 104 ±7%, 64 ± 3% and 61±22% respectively, while IGF-I, insulin and GH had little effect. In conclusion, IGF-I, and high concentrations of insulin, increased IGF-I mRNA in vascular smooth muscle cells, whereas factors which were stronger mitogens decreased IGF-I gene expression. Journal of Endocrinology (1990) 125, 381–386

scholarly journals Dairy cows experience selective reduction of the hepatic growth hormone receptor during the periparturient period

2004 ◽  
Vol 181 (2) ◽  
pp. 281-290 ◽  
Author(s):  
J Wook Kim ◽  
RP Rhoads ◽  
SS Block ◽  
TR Overton ◽  
SJ Frank ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Dairy Cows ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Late Pregnancy ◽  
Target Tissue ◽  
Ghr Gene ◽  
Igf I

At parturition, dairy cows experience a 70% reduction in plasma IGF-I. This reduction coincides with decreased abundance of GHR1A, the liver-specific transcript of the growth hormone receptor (GHR) gene, suggesting impaired growth hormone-dependent synthesis of IGF-I. It is not immediately obvious that the periparturient reduction in GHR1A is sufficient to reduce hepatic GHR abundance. This is because approximately 50% of total GHR mRNA abundance in prepartum liver is accounted for by ubiquitously expressed transcripts which remain collectively unchanged at parturition. In addition, the possibility that parturition alters GHR expression in other growth hormone target tissue has not been examined. To address these questions, we measured GHR gene expression and GHR protein in liver and skeletal muscle of four dairy cows on days -35,+3 and+56 (relative to parturition on day 0). Hepatic GHR abundance and GHR1A transcripts were lower on day+3 than on day -35 and returned to late pregnancy value by day+56. Additional studies in two other groups of cows indicated that the hepatic levels of the GHR protein recovered substantially within 10 days after parturition. These changes occurred without variation in the abundance of HNF4, a liver-enriched transcription factor activating the promoter responsible for GHR1A synthesis. In contrast to liver, levels of GHR gene expression and GHR protein were identical on days -35,+3 and+56 in skeletal muscle. These data suggest a role for the GHR in regulating tissue-specific changes in growth hormone responsiveness in periparturient dairy cows.

Performance of ewes given maize silage during late pregnancy and lactation

1999 ◽  
Vol 1999 ◽  
pp. 130-130 ◽  
Author(s):  
J. Hill ◽  
A.B. Notman ◽  
S.P. Marsh
Keyword(s):  
Late Pregnancy ◽  
Early Lactation ◽  
Maize Silage ◽  
The United Kingdom ◽  
Pregnancy And Lactation ◽  
Dietary Components ◽  
Sheep Production ◽  
High Degree ◽  
Selection Of

Maize silage is a popular feed for dairy and beef cattle in the United Kingdom, but its popularity for sheep production has never been great. Several reasons for the lack of interest in maize silage for ewes and lambs have been cited; the growth of an annual crop for silage on holdings with a predominance of long-term leys, the low requirement of ewes and lambs for conserved feed, the possibility of low voluntary DM intakes and the risk of a high degree of selection of dietary components of the diet (Brown and Thomas, 1989). The research reported here examines the use of maize silage for ewes in late pregnancy and early lactation.

scholarly journals Identifying growth hormone-regulated enhancers in the Igf1 locus

2015 ◽  
Vol 47 (11) ◽  
pp. 559-568 ◽  
Author(s):  
Damir Alzhanov ◽  
Aditi Mukherjee ◽  
Peter Rotwein
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Gene Transcription ◽  
Somatic Growth ◽  
Gene Promoters ◽  
Chromosomal Locus ◽  
Transcriptional Enhancers ◽  
Physiological Processes ◽  
Igf I ◽  
I Gene

Growth hormone (GH) plays a central role in regulating somatic growth and in controlling multiple physiological processes in humans and other vertebrates. A key agent in many GH actions is the secreted peptide, IGF-I. As established previously, GH stimulates IGF-I gene expression via the Stat5b transcription factor, leading to production of IGF-I mRNAs and proteins. However, the precise mechanisms by which GH-activated Stat5b promotes IGF-I gene transcription have not been defined. Unlike other GH-regulated genes, there are no Stat5b sites near either of the two IGF-I gene promoters. Although dispersed GH-activated Stat5b binding elements have been mapped in rodent Igf1 gene chromatin, it is unknown how these distal sites might function as potential transcriptional enhancers. Here we have addressed mechanisms of regulation of IGF-I gene transcription by GH by generating cell lines in which the rat Igf1 chromosomal locus has been incorporated into the mouse genome. Using these cells we find that physiological levels of GH rapidly and potently activate Igf1 gene transcription while stimulating physical interactions in chromatin between inducible Stat5b-binding elements and the Igf1 promoters. We have thus developed a robust experimental platform for elucidating how dispersed transcriptional enhancers control Igf1 gene expression under different biological conditions.

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