Regulation of plasma and tissue levels of insulin-like growth factor-I by nutrition and treatment with growth hormone in sheep

1993 ◽  
Vol 136 (2) ◽  
pp. 217-224 ◽  
Author(s):  
K. M. Hua ◽  
R. Ord ◽  
S. Kirk ◽  
Q. J. Li ◽  
S. C. Hodgkinson ◽  
...  

ABSTRACT Tissue and plasma levels of insulin-like growth factor-I (IGF-I), and relative levels of liver IGF-I RNA, were measured in 6-month-old ewe lambs which were well fed (n = 10) or starved (n = 10) for 5 days. Half of each nutrition group was given daily (09.00 h) injections of human GH (hGH; 0·15 mg/kg body weight per day). Blood was sampled daily from 09.00 to 12.00 h at 15-min intervals through jugular vein catheters and the lambs were slaughtered 24 h after the fifth injection of hGH. Tissue and plasma IGF-I was extracted using an acid-ethanol-cryo-precipitation technique and estimated by radioimmunoassay. Tissue IGF-I was corrected for retained plasma IGF-I using tissue and blood haemaglobin levels. Liver IGF-I RNA levels were monitored by in-situ hybridization. Plasma IGF-I (nmol/l) was higher in both the fed group and the fed group given GH treatment. Tissue IGF-I from kidneys (nmol/kg) was also higher (P < 0·001) in the fed group. There was no significant difference in IGF-I concentrations in the muscle biceps femoris or liver between fed and starved lambs. Although GH treatment did not increase IGF-I levels in tissues significantly, IGF-I RNA levels in liver were increased (P = 0·02) in both fed and starved animals. The relative liver IGF-I RNA levels positively correlated with their corresponding tissue IGF-I levels in the fed group and the fed group given GH treatment. The lack of a significant IGF-I response to GH in tissues may be due to either the time at which tissues were sampled after the GH treatment or the dose of GH administered. However, the higher IGF-I concentrations in plasma and kidney from fed compared with starved animals and the positive correlations between liver IGF-I and IGF-I RNA levels suggest that tissue and plasma IGF-I is regulated by nutrition and GH, with nutrition playing a critical role in the regulation of tissue and plasma IGF-I in normal lambs. Journal of Endocrinology (1993) 136, 217–224

2007 ◽  
Vol 292 (6) ◽  
pp. E1856-E1862 ◽  
Author(s):  
Yu Chen ◽  
Difei Sun ◽  
Vidya M. R. Krishnamurthy ◽  
Ralph Rabkin

Gram-negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced insulin-like growth factor-I (IGF-I) expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH-induced IGF-I expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied 4 h later. In liver of these animals, GH-induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic tumor necrosis factor-α and interleukin-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine-inducible suppressors of cytokine signaling-1 and -3 and cytokine-inducible SH2 protein (CIS). Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values and represent a potential cause of the reduced GH-induced IGF-I expression. In addition, binding of phosphorylated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-I gene transcription. Interestingly, when endotoxin-treated rats were treated with GH, there was a marked increase in proinflammatory cytokine gene expression in the liver. If such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients.


1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P &lt; 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.


1992 ◽  
Vol 132 (3) ◽  
pp. 339-344 ◽  
Author(s):  
S. R. Davis ◽  
S. C. Hodgkinson ◽  
C. G. Prosser ◽  
P. D. Gluckman ◽  
F. C. Buonomo ◽  
...  

ABSTRACT Plasma and mammary efferent lymph concentrations of insulin-like growth factor I (IGF-I) were determined in lactating ewes before and after treatment with GH (10 mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0·34 to 0·47 after GH treatment when the IGF-I content of plasma increased by 19·4 nmol/l (from 32·1 nmol/l) and lymph by 13·7 nmol/l (from 10·7 nmol/l). This increase in the relative content of IGF-I in lymph was associated with increased lymph content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by size exclusion chromatography. GH treatment increased the total binding capacity for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma and the 150 kDa pool in lymph but there was a proportionally greater increase in 50 kDa total binding in lymph relative to plasma. Further, GH treatment increased the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of the 150 kDa fraction, in both plasma and lymph. Ligand blot analysis of IGF-binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph. Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0·68 to 0·87. GH treatment of lactating ewes not only increased the IGF-I content of plasma but increased the apparent efficiency of transfer of IGF-I across capillary endothelium to mammary efferent lymph. Journal of Endocrinology (1992) 132, 339–344


1991 ◽  
Vol 128 (3) ◽  
pp. 457-463 ◽  
Author(s):  
C. G. Prosser ◽  
C. Royle ◽  
I. R. Fleet ◽  
T. B. Mepham

ABSTRACT Lactating goats exhibiting widely divergent responses to short-term (4 days) treatment with bovine GH (bGH) were retrospectively divided into two groups based on the magnitude of this response. There was no difference between groups in terms of the pretreatment milk yield, but by day 4 of treatment milk secretion had increased by 4·99±2·5 (s.e.m.) ml/h (P > 0·05 compared with pretreatment) for group 1 and 22·9±2·4 ml/h (P< 0·001) for group 2. Plasma GH increased in both groups, but concentrations were significantly higher both before and during treatment in group 1 compared with group 2. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly during bGH treatment for both groups and there was no significant difference between the two until day 4 of treatment when levels of IGF-I in group 1 began to decline, whereas those from group 2 were maintained. Concentrations of IGF-I in milk from goats in group 1 were not significantly altered by GH administration, whereas those in goats in group 2 were increased by 40% (P < 0·01 compared with pretreatment). Levels of IGF-I in mammary secretory tissue from four animals from group 1 were not altered by bGH (2·8±0·2 and 2·77 ±0·08 nmol/kg tissue before and after treatment respectively), but were significantly (P < 0·05) increased in four animals from group 2 (2·80±0·2 and 9·9±1·1 nmol/kg tissue). Thus, it appears that the galactopoietic response in goats was associated with significantly lower levels of GH in plasma after 3 days of treatment and, more strikingly, greater amounts of IGF-I in milk and mammary tissue. This latter observation is consistent with the hypothesis that the effects of bGH on the mammary gland itself are mediated by IGF-I and that the availability of IGF-I to mammary tissue is an important component of the overall galactopoietic response to bGH. Journal of Endocrinology (1991) 128, 457–463


2020 ◽  
Vol 7 (2) ◽  
pp. 102
Author(s):  
Abdullah Abdullah ◽  
Tjuk Imam Restiadi ◽  
Nunuk Dyah Retno Lastuti ◽  
Tita Damayanti ◽  
Wurlina Wurlina ◽  
...  

The purpose of the research was to know the effect of Insulin-Like Growth Factor-I (IGF-I) derived from pregnant crossbreed mare serum (PMS) in mice (Mus musculus) folliculogenesis. The subject of this research were 20 female mice. The research was arranged by Completely Randomized Design (CRD) with four treatments and five replications. The treatment were K0 = 10 ng/ml of physiological NaCl, P1 = 10 ng/ml of IGF-I PMS, P2 = 20 ng/ml of IGF-I PMS, and P3 = 40 ng/ml of IGF-I PMS. Observed variables are number of primary, secondary, tertiary and de Graff follicles. During the treatment the estrus cycle was also observed. The data of follicles number were analyzed by Analysis of Variance (ANOVA), followed by HSD (Honestly Significant Difference) test. The result showed that the addition of IGF-I PMS significantly affect (p<0,05) on increasing of the primary and secondary follicles number. The addition of IGF-I PMS 20 ng/ml and 40 ng/ml can increase the primary and secondary follicle significantly (p<0,05).


2017 ◽  
Vol 3 (6) ◽  
pp. 658
Author(s):  
Abdullah Abdullah ◽  
Tjuk IRestiadi ◽  
Nunuk DR Lastuti ◽  
Tita Damayanti ◽  
Wurlina Wurlina ◽  
...  

The purpose of the research was to know the effect of Insulin-Like Growth Factor-I (IGF-I) derived from pregnant crossbred mare serum (PMS) in mice (Mus musculus) folliculogenesis. The subjects of this research were 20 female mice. The research was arranged by Completely Randomized Design (CRD) with four treatments and five replications. The treatments were C0 = 10 ng/ml of physiological NaCl, P1 = 10 ng/ml of IGF-I PMS, P2 = 20 ng/ml of IGF-I PMS, and P3 = 40 ng/ml of IGF-I PMS. Observed variables are the number of primary, secondary, tertiary and de Graff follicles. During the treatment, the estrous cycle was also observed. The data of follicles number were analyzed by Analysis of Variance (ANOVA) and followed by HSD (Honestly Significant Difference) test. The result showed that the addition of IGF-I PMS significantly affects (p<0.05) on increasing the primary and secondary follicles number. The addition of IGF-I PMS 20 ng/ml and 40 ng/ml can increase the primary and secondary follicles significantly (p<0.05).  Keywords: IGF-I crossbreed mare serum pregnant; follicle; Mus musculus


2001 ◽  
Vol 21 (9) ◽  
pp. 2981-2990 ◽  
Author(s):  
Aimin Xu ◽  
Pann-Ghill Suh ◽  
Nelly Marmy-Conus ◽  
Richard B. Pearson ◽  
Oh Yong Seok ◽  
...  

ABSTRACT It is well established that a phosphoinositide (PI) cycle which is operationally distinct from the classical plasma membrane PI cycle exists within the nucleus, where it is involved in both cell proliferation and differentiation. However, little is known about the regulation of the nuclear PI cycle. Here, we report that nucleus-localized phospholipase C (PLC) β1, the key enzyme for the initiation of this cycle, is a physiological target of extracellular signal-regulated kinase (ERK). Stimulation of Swiss 3T3 cells with insulin-like growth factor I (IGF-I) caused rapid nuclear translocation of activated ERK and concurrently induced phosphorylation of nuclear PLC β1, which was completely blocked by the MEK inhibitor PD 98059. Coimmunoprecipitation detected a specific association between the activated ERK and PLC β1 within the nucleus. In vitro studies revealed that recombinant PLC β1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by PKA. The ERK phosphorylation site was mapped to serine 982, which lies within a PSSP motif located in the characteristic carboxy-terminal tail of PLC β1. In cells overexpressing a PLC β1 mutant in which serine 982 is replaced by glycine (S982G), IGF-I failed to activate the nuclear PI cycle, and its mitogenic effect was also markedly attenuated. Expression of S982G was found to inhibit ERK-mediated phosphorylation of endogenous PLC β1. This result suggests that ERK-evoked phosphorylation of PLC β1 at serine 982 plays a critical role in the activation of the nuclear PI cycle and is also crucial to the mitogenic action of IGF-I.


2006 ◽  
Vol 6 ◽  
pp. 53-80 ◽  
Author(s):  
N. David Åberg ◽  
Katarina Gustafson Brywe ◽  
Jörgen Isgaard

Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain. Some of the shared effects in common to GH and IGF-I may also be explained by cross-talk between the GH and IGF-I transduction pathways, as indicated by recent data from other cell systems. Otherwise, it also seems that GH may act directly without involving IGF-I (either circulating or locally). Plasticity in the central nervous system (CNS) may be viewed as changes in the functional interplay between the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I affect all three of these cell types in several ways. Apart from the neuroprotective effects of GH and IGF-I posited in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. It appears that the MAPK signaling pathway is required for IGF-I–stimulated proliferationin vitro, whereas the PI3K/Akt or MAPK/Erk signaling pathway appears to mediate antiapoptotic effects. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. The functional role of GH and IGF-I in the adult brain will be reviewed with reference to neurotransmitters, glucose metabolism, cerebral blood flow, gap junctional communication, dendritic arborization, exercise, enriched environment, depression, learning, memory, and aging.Briefly, these findings suggest that IGF-I functions as a putative regenerative agent in the adult CNS. Hitherto less studied regarding in these aspects, GH may have similar effects, especially as it is the main regulator of IGF-Iin vivo. Some of the positive cognitive features of GH treatment are likely attributable to the mechanisms reviewed here.


2020 ◽  
Vol 7 (2) ◽  
pp. 120
Author(s):  
Dyah Ayu Roro Risna Y ◽  
Sri Mulyati ◽  
Roesno Darsono ◽  
Imam Mustofa ◽  
Arimbi Arimbi ◽  
...  

The purpose of the research was to know  the effect of Insulin-Like Growth Factor-I (IGFI) derived from pregnant crossbreed mare serum (PMS) on endometrium thickness of mice (Mus musculus). The subject of this research were 35 female mice. The research was arranged by Completely Randomized Design (CRD) with seven treatment and five replications. The treatment were P0 = 10 ng/ml of physiological NaCl, P11 = 10 ng/ml of IGF-I PMS, P12 = 20 ng/ml of IGF-I PMS, P13 = 40 ng/ml of IGF-I PMS, P21 = 10 ng/ml of IGF-I recombinant mouse, P22 = 20 ng/ml of IGF-I recombinant mouse, and P23 = 40 ng/ml of IGF-I recombinant mouse. Observed variables include histopatological endometrium thickness of mice. The data were analyzed by Analysis of Variance (ANOVA), followed by HSD (Honestly Significant Difference) test. The data was also be analyzed using General Linear Model Univarieted to see the comparison between IGF-I PMS and recombinant mouse. The result showed that the addition of IGF-I PMS did not significantly affect (p>0,05) on endometrium thickness of mice . It showed that did not significantly difference (p>0,05) between the effect of IGF-I PMS and IGF-I recombinant mouse against the endometrium thickness of mice.


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