scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

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 < 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.

Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding

2007 ◽  
Vol 292 (6) ◽  
pp. E1856-E1862 ◽  
Author(s):  
Yu Chen ◽  
Difei Sun ◽  
Vidya M. R. Krishnamurthy ◽  
Ralph Rabkin
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Janus Kinase ◽  
Cytokine Gene Expression ◽  
Cytokine Signaling ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

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.

Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR), insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene expression of GH and GHR in rat pre-antral follicles

Zygote ◽  
2002 ◽  
Vol 10 (1) ◽  
pp. 85-94 ◽  
Author(s):  
J. Zhao ◽  
M.A.M. Taverne ◽  
G.C. van der Weijden ◽  
M.M. Bevers ◽  
R. van den Hurk
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Growth Factor ◽  
Follicular Development ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Antral Follicles ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

We previously demonstrated that the development of cultured rat pre-antral follicles is stimulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I) and that the mRNA of IGF-I and type I IGF receptor (IGFR) is present in the oocyte and wall of these follicles. To gain a closer insight into the regulation of early folliculogenesis by GH and IGF-I, the present study investigated the gene expression of GH and GHR mRNA in isolated oocytes and follicular wall cells of pre-antral follicles, using reverse transcriptase polymerase chain reaction, and the localisation of immunoreactive IGF-I, IGFR, GH and GHR proteins in ovarian sections of 10-day-old rats. GH was detected in oocytes and follicular wall tissue of pre-antral follicles, whereas expression of the GH mRNA was absent. The GHR mRNA was present in follicular wall tissue and not in the oocyte, while positive immunostaining for GHR was observed in all cells of the pre-antral follicles. Immunoreactive IGF-I and IGFR was also visible in the pre-antral follicles, especially in the oocytes. In conclusion, the data show that the previously demonstrated local gene expression of IGF-I and IGFR in oocytes and their enveloping follicular cells also leads to translation, which points to the involvement of intrafollicular IGF-I in early follicular development. The presence of the GHR mRNA and the GHR and GH proteins in pre-antral follicles in the absence of ovarian GH mRNA suggest a direct effect of systemic GH on early follicular development.

scholarly journals Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain

2006 ◽  
Vol 6 ◽  
pp. 53-80 ◽  
Author(s):  
N. David Åberg ◽  
Katarina Gustafson Brywe ◽  
Jörgen Isgaard
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Cell Types ◽  
Adult Brain ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

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.

Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation

1995 ◽  
Vol 268 (2) ◽  
pp. E318-E327 ◽  
Author(s):  
J. M. Lean ◽  
C. J. Jagger ◽  
T. J. Chambers ◽  
J. W. Chow
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Mechanical Stimulation ◽  
Matrix Protein ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Osteogenic Response ◽  
Igf I ◽  
Growth Factor I

We recently developed an experimental model whereby a single 10-min episode of mechanical stimulation induces bone formation in the eighth caudal vertebra of 13-wk-old rats. We used this model to relate the kinetics of the bone-forming response, as measured by administration of fluorescent markers, to an in situ hybridization analysis of changes in mRNA for two matrix proteins (type I collagen and osteocalcin) and a growth factor implicated in the regulation of bone formation [insulin-like growth factor I (IGF-I). We found that increased fluorochrome labeling was accompanied by an increase in the proportion of trabecular bone surfaces on which transcripts for collagen type I and osteocalcin were detectable, from < 3 to 25% 72 h after loading. IGF-I expression on trabecular surfaces showed a slightly earlier increase. We also noted intense hybridization for IGF-I in osteocytes in the diaphyseal cortex and in metaphyseal trabeculae. This was observed only in loaded bones, within 6 h of loading, and became undetectable in trabecular osteocytes 48 h and cortical osteocytes 120 h after loading. This is the first identification of a specific mRNA species in osteocytes after mechanical stimulation. Its production before the increase in transcription of matrix protein mRNA, and before the transcription of IGF-I mRNA in bone surface cells, represents persuasive evidence for a role for osteocytes, and for IGF-I, in the osteogenic response of bone to mechanical stimulation.

Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment

2009 ◽  
Vol 297 (3) ◽  
pp. F639-F645 ◽  
Author(s):  
Helena Gil-Peña ◽  
Enrique Garcia-Lopez ◽  
Oscar Alvarez-Garcia ◽  
Vanessa Loredo ◽  
Eduardo Carbajo-Perez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Mrna Expression ◽  
Growth Plate ◽  
Female Rats ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Hypokalemic tubular disorders may lead to growth retardation which is resistant to growth hormone (GH) treatment. The mechanism of these alterations is unknown. Weaning female rats were grouped ( n = 10) in control, potassium-depleted (KD), KD treated with intraperitoneal GH at 3.3 mg·kg−1·day−1 during the last week (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth retarded compared with CPF rats, the osseous front advance (±SD) being 67.07 ± 10.44 and 81.56 ± 12.70 μm/day, respectively. GH treatment did not accelerate growth rate. The tibial growth plate of KD rats had marked morphological alterations: lower heights of growth cartilage (228.26 ± 23.58 μm), hypertrophic zone (123.68 ± 13.49 μm), and terminal chondrocytes (20.8 ± 2.39 μm) than normokalemic CPF (264.21 ± 21.77, 153.18 ± 15.80, and 24.21 ± 5.86 μm). GH administration normalized these changes except for the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes in their distribution as analyzed by immunohistochemistry and in situ hybridization. GH did not further modify IGF-I mRNA expression. KD rats had normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses the structural and molecular alterations induced by potassium depletion on the growth plate and shows that the lack of response to GH administration is associated with persistence of the disturbed process of chondrocyte hypertrophy and depressed mRNA expression of local IGF-I in the growth plate.

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