Intrauterine Growth Retardation and Postnatal Growth Failure Associated with Deletion of the Insulin-Like Growth Factor I Gene

Woods, Katie A.; Camacho‐Hübner, Cecilia; Savage, Martin O.; Clark, Adrian

doi:10.1056/nejm199610313351805

Cited by 1,004 publications

(644 citation statements)

References 27 publications

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“…Our data show that changes in hypothalamic neurite density seen in mice with global GHR deletion are not replicated in mice with liver‐specific disruption of GHR, suggesting that the hypothalamic changes are not brought about by lower plasma IGF‐1 levels. Disruption of IGF‐1 gene expression during early life causes growth retardation and defects in the development of metabolic organs that can alter energy homeostasis throughout adult life (Woods et al ., 1996). GHR −/− mice have increased expression of hypothalamic IGF‐1 and IGF1R (Nyberg, 2000; Bartke, 2011), despite lower levels of plasma IGF‐1.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

et al. 2015

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SummaryMice in which the genes for growth hormone (GH) or GH receptor (GHR −/−) are disrupted from conception are dwarfs, possess low levels of IGF‐1 and insulin, have low rates of cancer and diabetes, and are extremely long‐lived. Median longevity is also increased in mice with deletion of hypothalamic GH‐releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6‐week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR −/− mice lead to reduced formation of both orexigenic agouti‐related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18‐month‐old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF‐1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF‐1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early‐life disruption of GH signaling produces long‐term hypothalamic changes that may contribute to the longevity of GH‐deficient and GH‐resistant mice.

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Section: Discussionmentioning

confidence: 99%

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

et al. 2015

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“…The severity of the foetal growth restriction is illustrated with birth weight standard deviation scores (SDS) ranging from −2.5 to −3.5 (Table 1) 36, 37, 38, 39, 40.…”

Section: Organ‐specific Roles Of Igf‐1 In the Foetusmentioning

confidence: 99%

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

et al. 2016

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Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin‐like growth factor 1 (IGF‐1) axis is the major hormonal mediator of growth in utero, and levels of IGF‐1 are often very low after preterm birth. We reviewed the role of IGF‐1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF‐1 deficiency in preterm morbidities.ConclusionThere is a rationale for clinical trials to evaluate the potential benefits of IGF‐1 replacement in very preterm infants.

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“…(1)(2)(3)11) A role of IGF-1 in bone metabolism is supported by the fact that patients with IGF deficiency as a result of IGF1 gene deletion or inactivating mutation display osteopenia. (12)(13)(14) The association between serum IGF-1 and BMD has been evaluated in several cohorts but with conflicting results. (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) A positive association has been reported in some studies, (15,17,(20)(21)(22)(23)25,26) whereas no association has been found in other studies.…”

Section: Introductionmentioning

confidence: 99%

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

Ohlsson

Mellström

Carlzon

et al. 2010

Journal of Bone and Mineral Research

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Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear. To determine the predictive value of serum IGF-1 for fracture risk in men, older men (n ¼ 2902, mean age of 75 years) participating in the prospective, population-based Osteoporotic Fractures in Men (MrOS) Sweden study were followed for a mean of 3.3 years. Serum IGF-1 was measured at baseline by radioimmunoassay. Fractures occurring after the baseline visit were validated. In age-adjusted hazards regression analyses, serum IGF-1 associated inversely with risk of all fractures [hazard ratio (HR) per SD decrease ¼ 1.23, 95% confidence interval (CI) 1.07-1.41], hip fractures (HR per SD decrease ¼ 1.45, 95% CI 1.07-1.97), and clinical vertebral fractures (HR per SD decrease ¼ 1.40, 95% CI 1.10-1-78). The predictive role of serum IGF-1 for fracture risk was unaffected by adjustment for height, weight, prevalent fractures, falls, and major prevalent diseases. Further adjustment for bone mineral density (BMD) resulted in an attenuated but still significant association between serum IGF-1 and fracture risk. Serum IGF-1 below but not above the median was inversely related to fracture incidence. The population-attributable risk proportion was 7.5% for all fractures and 22.9% for hip fractures. Taken together, older men with low serum IGF-1 have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. The association between serum IGF-1 and fracture risk is partly mediated via BMD. ß

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Intrauterine Growth Retardation and Postnatal Growth Failure Associated with Deletion of the Insulin-Like Growth Factor I Gene

Cited by 1,004 publications

References 27 publications

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

Insulin‐like growth factor 1 has multisystem effects on foetal and preterm infant development

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

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