scholarly journals Sensitivity to exogenous GH and reversibility of the reduced IGF-I gene expression in aging rats

2001 ◽  
pp. 73-85 ◽  
Author(s):  
B Velasco ◽  
L Cacicedo ◽  
E Melian ◽  
G Fernandez-Vazquez ◽  
F Sanchez-Franco
Keyword(s):  
Gene Expression ◽  
Young Adult ◽  
Mrna Level ◽  
Young Group ◽  
Male Rats ◽  
Middle Aged ◽  
Igf I ◽  
Old Rats ◽  
Rhgh Treatment ◽  
I Gene

BACKGROUND: IGF-I gene expression and IGF-I plasma concentration decline with age. A decreased sensitivity to GH has been suggested to be a contributory mechanism to this, in addition to attenuated GH secretion. OBJECTIVE: This study focuses on the sensitivity to exogenous GH and the reversibility of the reduced IGF-I gene expression in aging male rats. DESIGN: Three groups of male Wistar rats aged 3 months (young adult), 11 months (middle-aged) and 27 months (old), received recombinant human GH (rhGH) (150 microg/12 h s.c.) for seven consecutive days. RESULTS: This rhGH treatment completely reversed plasma immunoreactive IGF-I (IR-IGF-I) and hepatic IGF-I mRNA levels in 11-month-old and 27-month-old animals to the levels of the young group of animals. The sensitivity in the old group (percentage of increment after the same or lower dose of rhGH per body weight) was increased for both parameters; serum IGF-I increment: 15% in 3-month-old, 42.6% in 11-month-old and 119.1% in 27-month-old rats; and hepatic IGF-Ib mRNA increase: 45% in 3-month-old, 27.8% in 11-month-old and 64.3% in 27-month-old rats. IGF binding protein-3 (IGFBP-3) mRNA level in the liver was significantly decreased in the old group and only a partial reversion occurred in this group after rhGH treatment; the percentage of increment was also higher in the old group of rats. In extrahepatic tissues IGF-I mRNA was not significantly different in the kidney and the testis of the three groups, and the rhGH treatment produced a significant and similar increase of IGF-I mRNA level in the kidney of the three groups of rats and in the testis of the 27-month-old animals. The GHr/GHBP mRNA remained unchanged in the liver and in the kidney or the testis of the three groups, and was not influenced by the rhGH treatment. Exogenous rhGH decreased pituitary GH mRNA accumulation in a more intense manner in the old group versus control of each group: young adult, 25%; middle-aged, 41.2%; and old rats, 55%. The action of rhGH on pituitary immunoreactive GH (IR-GH) content was only significantly evident in the young group. CONCLUSIONS: These results establish that exogenous rhGH recovers the attenuated liver IGF-I gene expression and the diminished plasma IR-IGF-I in old rats to the levels of young adult animals. They also indicate that the hepatic and extrahepatic (kidney and testis) sensitivity to one established dose per weight of exogenous rhGH is not altered in old animals, or could be potentially increased in some tissues.

scholarly journals Functional deficits and insulin-like growth factor-I gene expression following tourniquet-induced injury of skeletal muscle in young and old rats

2008 ◽  
Vol 105 (4) ◽  
pp. 1274-1281 ◽  
Author(s):  
David W. Hammers ◽  
Edward K. Merritt ◽  
Wayne Matheny ◽  
Martin L. Adamo ◽  
Thomas J. Walters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Intracellular Signaling ◽  
Ischemia Reperfusion ◽  
Force Production ◽  
Histological Evaluation ◽  
Igf I ◽  
Old Rats ◽  
I Gene ◽  
Recovery Groups

This study investigated the effect of age on recovery of skeletal muscle from an ischemia-reperfusion (I/R)-induced injury. Young (6 mo old) and old (24–27 mo old) Sprague-Dawley rats underwent a 2-h bout of hindlimb ischemia induced by a pneumatic tourniquet (TK). The TK was released to allow reperfusion of the affected limb, and animals were divided into 7- and 14-day recovery groups. Maximum plantar flexor force production was assessed in both 7- and 14-day recovery groups of both ages, followed by histological evaluation. Subsequent analysis of IGF-I gene expression and intracellular signaling in 7-day recovery muscles was performed by RT-PCR and Western blotting, respectively. Old rats had significantly greater deficits in force production and exhibited more evidence of histological pathology than young at both 7 and 14 days postinjury. In addition, old rats demonstrated an attenuated upregulation of IGF-I mRNA and induction of proanabolic signaling compared with young in response to injury. We conclude that aged skeletal muscle exhibits more damage and/or defective regeneration following I/R and identify an age-associated decrease in local IGF-I responsiveness as a potential mechanism for this phenomenon.

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 Differential effects of targeted tongue exercise and treadmill running on aging tongue muscle structure and contractile properties

2013 ◽  
Vol 114 (4) ◽  
pp. 472-481 ◽  
Author(s):  
Heidi Kletzien ◽  
John A. Russell ◽  
Glen E. Leverson ◽  
Nadine P. Connor
Keyword(s):  
Young Adult ◽  
Exercise Group ◽  
Contractile Properties ◽  
Treadmill Running ◽  
Brown Norway ◽  
Middle Aged ◽  
Adult Rats ◽  
Tongue Muscle ◽  
Muscle Structure ◽  
Old Rats

Age-associated changes in tongue muscle structure and strength may contribute to dysphagia in elderly people. Tongue exercise is a current treatment option. We hypothesized that targeted tongue exercise and nontargeted exercise that activates tongue muscles as a consequence of increased respiratory drive, such as treadmill running, are associated with different patterns of tongue muscle contraction and genioglossus (GG) muscle biochemistry. Thirty-one young adult, 34 middle-aged, and 37 old Fischer 344/Brown Norway rats received either targeted tongue exercise, treadmill running, or no exercise (5 days/wk for 8 wk). Protrusive tongue muscle contractile properties and myosin heavy chain (MHC) composition in the GG were examined at the end of 8 wk across groups. Significant age effects were found for maximal twitch and tetanic tension (greatest in young adult rats), MHCIIb (highest proportion in young adult rats), MHCIIx (highest proportion in middle-aged and old rats), and MHCI (highest proportion in old rats). The targeted tongue exercise group had the greatest maximal twitch tension and the highest proportion of MHCI. The treadmill running group had the shortest half-decay time, the lowest proportion of MHCIIa, and the highest proportion of MHCIIb. Fatigue was significantly less in the young adult treadmill running group and the old targeted tongue exercise group than in other groups. Thus, tongue muscle structure and contractile properties were affected by both targeted tongue exercise and treadmill running, but in different ways. Studies geared toward optimizing dose and manner of providing targeted and generalized tongue exercise may lead to alternative tongue exercise delivery strategies.

scholarly journals Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243499
Author(s):  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
Natalie Pinkowski ◽  
Lama Almaiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Young Adult ◽  
Cell Growth ◽  
Alcohol Consumption ◽  
Ethanol Consumption ◽  
Ethanol Treatment ◽  
Middle Aged

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

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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