Growth Hormone/Insulin-Like Growth Factor-1/PTH Axis in Bone

Bikle, Daniel D.

doi:10.1359/jbmr.080111

Cited by 12 publications

(6 citation statements)

References 48 publications

(76 reference statements)

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“…Even though IGF1 was inversely related to age and kidney function in univariate analysis as has been previously shown [10], IGF1 remained significant in multivariate analysis in men but did not quite reach significance for women. Our findings are of interest in the light of growing evidence that GH/IGF1 and PTH have synergistic actions on bone [14–16].…”

Section: Discussionmentioning

confidence: 98%

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

Gunnarsson¹,

Indridason²,

Franzson

et al. 2009

Journal of Internal Medicine

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Objectives. The purpose of this study was to examine factors associated with high or low parathyroid hormone (PTH) levels in relationship to vitamin D insufficiency.Design. This was a cross-sectional study consisting of 516 healthy men and women, aged 30-85, all Caucasians with vitamin D insufficiency [serum 25(OH)D < 45 nmol L )1 ]. The group was divided into quartiles by PTH levels and the highest and lowest quartiles were compared with regard to various factors likely to affect calcium metabolism. We used stepwise multivariable logistic regression to determine the independent association between PTH levels and other variables for men and women separately.Results. We found that men in the lowest PTH quartile were significantly younger, had less energy intake, lower body mass index (BMI) and better kidney function compared with the highest PTH quartile. They had also higher ionized calcium, insulin-like growth factor (IGF1) and testosterone and were more likely to smoke. Women within the lowest PTH quartile were younger, had lower BMI and magnesium values and higher IGF1 levels and were more likely to smoke. Stepwise multivariate regression showed that IGF1, testosterone and BMI were significantly associated with PTH in men (R 2 = 0.472) but smoking, BMI and kidney function in women (R 2 = 0.362). Conclusions.Our results indicate that during vitamin D insufficiency, factors other than calcium and vitamin D may modify PTH response. These factors may be different between sexes and we have identified novel factors, IGF1 and testosterone in men which may be compensatory in nature and confirmed previous factors such as smoking, BMI and kidney function in women.

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Section: Discussionmentioning

confidence: 98%

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

Gunnarsson¹,

Indridason²,

Franzson

et al. 2009

Journal of Internal Medicine

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“…Although some data have suggested a potential pro-carcinogenic role of PTH (40)(41)(42) (potential mitogenic activity in preneoplastic lesions), others support a potential protective role. Indeed, high PTH concentration may decrease growth hormone secretion, thereby decreasing circulating insulin-like growth factor-1 (IGF-1) concentration (43,44) ; IGF-1 being considered as a potential risk factor for prostate cancer (45,46) . Thus, further investigation is needed on the association between PTH concentration and prostate cancer risk.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk

et al. 2015

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Mechanistic hypotheses suggest that vitamin D and the closely related parathyroid hormone (PTH) may be involved in prostate carcinogenesis. However, epidemiological evidence is lacking for PTH and inconsistent for vitamin D. Our objectives were to prospectively investigate the association between vitamin D status, vitamin D-related gene polymorphisms, PTH and prostate cancer risk. A total of 129 cases diagnosed within the Supplémentation en Vitamines et Minéraux Antioxydants cohort were included in a nested case-control study and matched to 167 controls (13 years of follow-up). 25-Hydroxyvitamin D (25(OH)D) and PTH concentrations were assessed from baseline plasma samples. Conditional logistic regression models were computed. Higher 25(OH)D concentration was associated with decreased risk of prostate cancer (OR Q4 v. Q1 0·30; 95 % CI 0·12, 0·77; P trend = 0·007). PTH concentration was not associated with prostate cancer risk (P trend = 0·4) neither did the studied vitamin D-related gene polymorphisms. In this prospective study, prostate cancer risk was inversely associated with 25(OH)D concentration but not with PTH concentration. These results bring a new contribution to the understanding of the relationship between vitamin D and prostate cancer, which deserves further investigation.

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“…The downregulation of IRS1 expression not only reduced cell survival and proliferation, but also impaired cell differentiation in MC3T3-E1 cells (ALP activity and the expression of both osteocalcin and type I collagen mRNA and protein were all decreased), which suggested that IRS1 can increase the bone formation by promoting the proliferation and differentiation of preosteoblasts and increase the bone matrix by producing more collagen. Although the mechanism by which IRS1 increases the cell proliferation and differentiation needs to be further studied, it is known that IRS1 is the major substrate of insulin and IGF1 receptors, which play important roles in bone metabolism (Bikle 2008, Giustina et al 2008, IRS1 gene silencing in osteoblast obviously inhibited the AKT phosphorylation (Fig. 1), and AKT is the direct target of IGF1 in IRS1 signal pathway.…”

Section: Discussionmentioning

confidence: 99%

Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells

Bu¹,

He²,

Zhou³

et al. 2010

Journal of Endocrinology

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Insulin receptor substrate 1 (IRS1) is an essential molecule for the intracellular signaling of IGF1 and insulin, which are potent anabolic regulators of bone metabolism. Osteoblastic IRS1 is essential for maintaining bone turnover; however, the mechanism underlying this regulation remains unclear. To clarify the role of IRS1 in bone metabolism, we employed RNA interference to inhibit IRS1 gene expression and observed the effects of silencing this gene on the proliferation and differentiation of and the expression of matrix metallopeptidase (MMP) and tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) in MC3T3-E1 cells. Our results showed that IRS1 short hairpin RNAs can effectively suppress the expression of IRS1, and inhibit the phosphorylation of AKT in IRS1 pathway; reduce the expression of MMP2, MMP3, MMP13, and MMP14, decrease the expression of TNFRSF11B and RANKL (also known as tumor necrosis factor (ligand) superfamily, member 11), however increase the RANKL/TNFRSF11B ratio; decrease cell survival, proliferation, and mineralization, and impair the differentiation of MC3T3-E1 cells. The downregulation of IRS1 had no effect on the expression of MMP1. Our findings suggest that IRS1 not only promotes bone formation and mineralization but also might play roles in bone resorption partly via the regulation of MMPs and RANKL/TNFRSF11B ratio, thus regulates the bone turnover.

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Growth Hormone/Insulin-Like Growth Factor-1/PTH Axis in Bone

Cited by 12 publications

References 48 publications

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

Factors associated with elevated or blunted PTH response in vitamin D insufficient adults

A prospective study of plasma 25-hydroxyvitamin D concentration and prostate cancer risk

Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells

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