Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.

Courtland HW, Sun H, Beth-On M, Wu Y, Elis S, Rosen CJ, Yakar S

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research1 Apr 2011Cited by 26 (Europe PMC)

PMID20928887PMCIDPMC3179330DOI10.1002/jbmr.265PepBankPUB-20928887

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Summary

Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant significantly reduced body weight compared with vehicle-treated LID mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced body weight compared with vehicle.
Peptide
Pegvisomant
Outcome
DecreaseBody weight
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Vehicle-treated LID mice
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888701
02AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant significantly reduced femur length compared with vehicle-treated LID mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced femur length compared with vehicle.
Peptide
Pegvisomant
Outcome
DecreaseFemur length
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Vehicle-treated LID mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888702
03AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant significantly reduced femur total area compared with vehicle-treated LID mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced femur total area compared with vehicle.
Peptide
Pegvisomant
Outcome
DecreaseFemur total area
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Vehicle-treated LID mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888703
04AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant further reduced serum IGF-1 by 8 weeks of age compared with vehicle-treated LID mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced serum IGF-1 compared with vehicle.
Peptide
Pegvisomant
Outcome
DecreaseSerum IGF-1
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Vehicle-treated LID mice
Outcome group
Growth hormone and IGF-1 · Endocrine and hormones
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice.
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888704
05AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, femur total area and length reductions were proportional after pegvisomant treatment.
In plain wordsIn mice with liver-specific IGF-1 deficiency, femur area and length decreased proportionally after pegvisomant treatment.
Peptide
Pegvisomant
Outcome
Not applicableProportional femur area and length reductions
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant.
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888705
06AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant significantly reduced relative cortical tissue formed compared with vehicle-treated LID mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced relative cortical tissue formation compared with vehicle-treated deficient mice.
Peptide
Pegvisomant
Outcome
DecreaseRelative cortical tissue formed
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Vehicle-treated LID mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice,
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888706
07AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant significantly reduced relative cortical tissue formed compared with control mice.
In plain wordsIn mice with liver-specific IGF-1 deficiency, pegvisomant reduced relative cortical tissue formation compared with control mice.
Peptide
Pegvisomant
Outcome
DecreaseRelative cortical tissue formed
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Comparator
Control mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice,
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888707
08AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant treatment resulted in markedly decreased femoral whole-bone stiffness.
In plain wordsIn mice with liver-specific IGF-1 deficiency, femoral whole-bone stiffness decreased after pegvisomant treatment.
Peptide
Pegvisomant
Outcome
DecreaseFemoral whole-bone stiffness
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased)
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888708
09AnimalAnimal study (in vivo)Efficacy outcome
In male LID mice, pegvisomant treatment resulted in markedly decreased femoral work to failure.
In plain wordsIn mice with liver-specific IGF-1 deficiency, the work needed to break the femur decreased after pegvisomant treatment.
Peptide
Pegvisomant
Outcome
DecreaseWork to failure
Study
mousen: not reported in source
Male liver-specific IGF-1-deficient mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated · from 4 to 8 weeks of ageAs given in this study (mouse).
Source sentences
Summary
This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased)
1 context sentence(design, population, supporting numbers)
Summary · context
To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age.
Show in the study text Report a problemFND-2092888709

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:34 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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