Moderate Food Restriction Abolishes the Pregnancy-Associated Rise in Serum Growth Hormone and Decreases Serum Insulin-Like Growth Factor-I (IGF-I) Concentrations without Altering IGF-I mRNA Expression in Rats

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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Somatostatin inhibits hepatic growth hormone receptor and insulin-like growth factor I mRNA expression by activating the ERK and PI3K signaling pathways

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00099.2008 ◽

2008 ◽

Vol 295 (2) ◽

pp. R490-R497 ◽

Cited By ~ 12

Author(s):

Alison L. Hagemeister ◽

Mark A. Sheridan

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Protein Kinase ◽

Mrna Expression ◽

Growth Hormone Receptor ◽

Mitogen Activated Protein Kinase ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I

Previously, we reported that somatostatins (SS) inhibit organismal growth by reducing hepatic growth hormone (GH) sensitivity and by inhibiting insulin-like growth factor I (IGF-I) production. In this study, we used hepatocytes isolated from rainbow trout to elucidate the mechanism(s) associated with the extrapituitary growth-inhibiting actions of SS. SS-14, a predominant SS isoform, stimulated tyrosine phosphorylation of several endogenous proteins, including extracellular signal-regulated kinase (ERK), a member the mitogen-activated protein kinase (MAPK) family, and protein kinase B (Akt), a downstream target of phosphatidylinositol 3-kinase (PI3K). SS-14 specifically stimulated the phosphorylation of both ERK 1/2 and Akt in a concentration-dependent fashion. This activation occurred within 5–15 min, then subsided after 1 h. The ERK inhibitor U0126 retarded SS-14-stimulated phosphorylation of ERK 1/2, whereas the PI3K inhibitor LY294002 blocked SS-14-stimulated phosphorylation of Akt. SS-14-inhibited expression of GH receptor (GHR) mRNA was blocked by U0126 but not by LY294002. By contrast, U1026 had no effect on SS-14 inhibition of GH-stimulated IGF-I mRNA expression, whereas LY294002 partially blocked the inhibition of GH-stimulated IGF-I mRNA expression by SS-14. These results indicate that SS-14-inhibited GHR expression is mediated by the ERK signaling pathway and that the PI3K/Akt pathway mediates, at least in part, SS-14 inhibition of GH-stimulated IGF-I expression.

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Serum Insulin-like Growth Factor-I (IGF-I) Levels During Long-term IGF-I Treatment of Children and Adults with Primary GH Resistance (Laron Syndrome)

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.1999.12.2.145 ◽

1999 ◽

Vol 12 (2) ◽

Cited By ~ 4

Author(s):

Z. Laron ◽

B. Klinger ◽

A. Silbergeld

Keyword(s):

Growth Factor ◽

Serum Insulin ◽

Insulin Like Growth Factor ◽

Laron Syndrome ◽

Factor I ◽

Igf I ◽

Growth Factor I ◽

Gh Resistance

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Effect of exogenous chicken growth hormone (cGH) administration on insulin-like growth factor-I (IGF-I) gene expression in domestic fowl

Molecular and Cellular Endocrinology ◽

10.1016/0303-7207(95)96796-k ◽

1995 ◽

Vol 114 (1-2) ◽

pp. 157-166 ◽

Cited By ~ 29

Author(s):

G Rosselot

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Growth Factor ◽

Domestic Fowl ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I ◽

I Gene

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Age-related plasma concentrations of growth hormone (GH) and insulin-like growth factor I(IGF-I) in great dane pups fed different dietary levels of protein

Domestic Animal Endocrinology ◽

10.1016/0739-7240(93)90028-a ◽

1993 ◽

Vol 10 (3) ◽

pp. 237-247 ◽

Cited By ~ 37

Author(s):

R.C. Nap ◽

J.A. Mol ◽

H.A.W. Hazewinkel

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Plasma Concentrations ◽

Insulin Like Growth Factor ◽

Factor I ◽

Age Related ◽

Igf I ◽

Growth Factor I ◽

Great Dane

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Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I

Physiological Genomics ◽

10.1152/physiolgenomics.00247.2005 ◽

2006 ◽

Vol 26 (1) ◽

pp. 46-54 ◽

Cited By ~ 22

Author(s):

Philip Hanlon ◽

William Andrew Lorenz ◽

Zhihong Shao ◽

James M. Harper ◽

Andrzej T. Galecki ◽

...

Keyword(s):

Growth Factor ◽

Serum Insulin ◽

Genome Scan ◽

Chromosome 17 ◽

Insulin Like Growth Factor ◽

Mouse Population ◽

Factor I ◽

A Genome ◽

Igf I ◽

Growth Factor I

A previous analysis of serum insulin-like growth factor I (IGF-I) levels in a mouse population ( n = 961) derived from a cross of (BALB/cJ × C57BL/6J) F1 females and (C3H/HeJ × DBA/2J) F1 males documented quantitative trait loci (QTL) on chromosomes 1, 10, and 17. We employed a newly developed, random walk-based method to search for three- and four-way allelic combinations that might influence IGF-I levels through nonadditive (conditional or epistatic) interactions among 185 genotyped biallelic loci and with significance defined by experiment-wide permutation ( P < 0.05). We documented a three-locus combination in which an epistatic interaction between QTL on paternal-derived chromosomes 5 and 18 had an opposite effect on the phenotype based on the allele inherited at a third locus on maternal-derived chromosome 17. The search also revealed three four-locus combinations that influence IGF-I levels through nonadditive genetic interactions. In two cases, the four-allele combinations were associated with animals having high levels of IGF-I, and, in the third case, a four-allele combination was associated with animals having low IGF-I levels. The multiple-locus genome scan algorithm revealed new IGF-I QTL on chromosomes 2, 4, 5, 7, 8, and 12 that had not been detected in the single-locus genome search and showed that levels of this hormone can be regulated by complex, nonadditive interactions among multiple loci. The analysis method can detect multilocus interactions in a genome scan experiment and may provide new ways to explore the genetic architecture of complex physiological phenotypes.

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