| 11. |
- McBeth, John, et al.
(författare)
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Perturbed Insulin-like Growth Factor-1 (IGF-1) and IGF Binding Protein-3 Are Not Associated with Chronic Widespread Pain in Men: Results from the European Male Ageing Study.
- 2009
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 36, s. 2523-2530
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether perturbations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) were associated with the presence of chronic widespread pain (CWP) in men. METHODS: The European Male Ageing Study (EMAS) is an 8-center population-based study of men aged 40-79 years recruited from population registers. A questionnaire asked about the presence and duration of musculoskeletal pain, from which subjects reporting CWP were identified. Subjects also had an interviewer-assisted questionnaire: levels of physical activity and mood were assessed, and height and weight were measured. IGF-1 and IGFBP-3 were assayed from a fasting blood sample. Logistic regression models were used to determine the association between IGF measures and CWP. Results were expressed as odds ratios or relative risk ratios. RESULTS: A total of 3206 subjects provided full data. Of those, 1314 (39.0%) reported no pain in the past month and 278 (8.3%) reported pain that satisfied criteria for CWP. IGF-1 concentrations were similar among subjects who reported no pain and those with CWP: 131.5 mg/l and 128.4 mg/l, respectively. This was true also for IGFBP-3 (4.3 and 4.3 mg/l). Obesity was associated with low IGF-1 and a high IGFBP-3/IGF-1 ratio, indicating less bioavailable IGF-1, irrespective of pain status. This relationship persisted after adjustment for comorbidities, depression, smoking, alcohol consumption, and quality of life. CONCLUSION: Overall CWP was not associated with perturbations in IGF-1 and IGFBP-3 concentrations. Hypofunctioning of the axis was noted among subjects who were obese and this was not specific to CWP. These data suggest that IGF-1 is unlikely to be etiologically important in relation to CWP, although the relationship with growth hormone remains to be elucidated.
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| 12. |
- O'Connor, Daryl B, et al.
(författare)
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Assessment of sexual health in aging men in Europe: Development and validation of the European Male Ageing Study sexual function questionnaire
- 2008
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 5:6, s. 1374-1385
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. Aim. The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study-sexual function questionnaire (EMAS-SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). Method. One thousand six hundred men aged 40-79 years completed the self-administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35-74 years completed the EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the instrument. Main Outcome Measures. Scores on the EMAS-SFQ in relation to age and T levels. Results. Principal component analysis showed that the EMAS-SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test-retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. Conclusion. The EMAS-SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging.
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| 13. |
- Ophoff, Jill, et al.
(författare)
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Physical activity in the androgen receptor knockout mouse: evidence for reversal of androgen deficiency on cancellous bone.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 378:1, s. 139-44
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Tidskriftsartikel (refereegranskat)abstract
- Disruption of the androgen receptor (AR) in male mice reduces cortical bone expansion and muscle mass during puberty and results in high bone turnover-related cancellous osteopenia. We hypothesized that voluntary wheel running during growth is able to rescue the effects of AR disruption on bone. To this end, 5-week-old AR knockout (ARKO) mice were randomized to a running group (cage with running wheel) and a sedentary group (cage without wheel) and followed-up until 16 weeks of age. Voluntary wheel running in ARKO mice did not influence body weight, muscle mass or periosteal bone expansion. Interestingly, voluntary running significantly reduced bone turnover in ARKO mice and prevented cancellous bone loss due to a preservation of trabecular number. Thus, voluntary running in ARKO mice was able to reduce cancellous bone resorption, suggesting that sustained exercise may potentially compensate the effects of androgen disruption on cancellous bone.
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| 14. |
- Vanderschueren, Dirk, et al.
(författare)
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Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.
- 2005
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Ingår i: Endocrine development. - Basel : KARGER. - 1421-7082. ; 8, s. 150-65
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Tidskriftsartikel (refereegranskat)abstract
- During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.
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| 15. |
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| 16. |
- Venken, Katrien, et al.
(författare)
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Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model.
- 2005
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 36:4, s. 663-70
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Tidskriftsartikel (refereegranskat)abstract
- This study reports the preclinical evaluation of the bone and muscle protective potential of the synthetic androgen 7alpha-methyl-19-nortestosterone (MENTtrade mark), as assessed in the aged orchidectomized rat model. Aged (13-month-old) orchidectomized Wistar rats were treated with different doses of MENT (4, 12 or 36 microg/day) subcutaneously for 16 weeks via mini-osmotic pumps. Analysis of the effects of androgen deficiency versus MENT replacement was performed using quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DEXA) and biochemical markers of bone turnover. At the end of the study period, prostate weight in orchidectomized rats treated with low- (4 microg/day) or mid-dose (12 mug/day) MENT remained significantly lower compared to the sham-operated animals (-47% and -25%, respectively). High-dose MENT (36 microg/day), on the other hand, induced prostate hypertrophy (+21% versus sham). Low-, mid- and high-dose MENT were found to be effective in suppressing the acceleration of bone remodeling following orchidectomy, as assessed by osteocalcin and deoxypyridinoline. In addition, low-, mid- and high-dose were able to prevent the orchidectomy-induced bone loss, as evaluated by DEXA at the femur and total-body and by pQCT at the femur. Compared to sham-operated animals, the low- and mid-dose MENT groups showed no decline in lean body mass and no muscle atrophy (as measured by m. quadriceps weight) at 16 weeks, whereas high-dose MENT was associated with a significant decline in lean body mass (-8.5% versus sham) and quadriceps weight (-10.6%). We conclude that, in the aged orchidectomized rat model, low- and mid-doses of the synthetic androgen MENT have bone and muscle protective effects and do not induce prostate hypertrophy. The bone protective action of high-dose MENT, however, occurs at the expense of muscle wasting and prostate hypertrophy. Our findings support the need for human studies to explore the potential of MENT as an option for androgen replacement in aging men.
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| 17. |
- Venken, Katrien, et al.
(författare)
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Growth without growth hormone receptor: estradiol is a major growth hormone-independent regulator of hepatic IGF-I synthesis.
- 2005
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 20:12, s. 2138-49
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Tidskriftsartikel (refereegranskat)abstract
- The role of estrogens in the regulation of pubertal growth independently of GH and its receptor was studied in male mice with disrupted GHRKO. E(2) rescued skeletal growth rates in GHRKO associated with an increase in hepatic and serum IGF-I. These data show that E(2) rescues pubertal growth during GH resistance through a novel mechanism of GHR-independent stimulation of hepatic IGF-I production. INTRODUCTION: Growth hormone (GH) and estrogen play a pivotal role in pubertal growth and bone mineral acquisition. Estrogens can affect GH secretion and thereby provide a GH-dependent mechanism for their effects on skeletal growth. It is presently unclear if or to what extent estrogens are able to regulate pubertal growth and bone mineral accrual independently of GH and its receptor. MATERIALS AND METHODS: Estradiol (E(2); 0.03 mug/day by subcutaneous silastic implants) was administered to orchidectomized (ORX) male mice with disrupted GHR (GHRKO) and corresponding WTs during late puberty (6-10 weeks). Longitudinal and radial bone growth, IGF-I in serum and its expression in liver, muscle, and bone, and liver gene expression were studied by histomorphometry, RIA, RT-PCR, microarrays, and Western blotting, respectively. RESULTS: E(2) stimulated not only longitudinal (femur length and growth plate thickness) and radial growth (cortical thickness and periosteal perimeter), but also rescued longitudinal and periosteal growth rates in ORX GHRKO, whereas no significant changes occurred in WT. E(2) thereby upregulated serum IGF-I and liver IGF-I synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas IGF-I synthesis in femur or muscle was unaffected. Study of the underlying mechanism of the stimulation of hepatic IGF-I expression showed that E(2) restored downregulated receptor signaling systems, such as the estrogen receptor alpha and the prolactin receptor. E(2) thereby recovered the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway as evidenced by a significantly increased activation of the transcription factor STAT5 in ORX GHRKO. CONCLUSIONS: Our data show a stimulation of skeletal growth through upregulation of hepatic IGF-I by a hormone other than GH. E(2) rescues pubertal skeletal growth during GH resistance through a novel mechanism of GHR-independent stimulation of IGF-I synthesis in the liver.
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| 18. |
- Venken, Katrien, et al.
(författare)
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Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty.
- 2007
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 22:1, s. 72-82
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between androgens and GH/IGF-I was studied in male GHR gene disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and cortical bone modeling and increase muscle mass even in the absence of a functional GHR. GHR activation seems to be the main determinant of radial bone expansion, although GH and androgens are both necessary for optimal stimulation of periosteal growth during puberty. INTRODUCTION: Growth hormone (GH) is considered to be a major regulator of postnatal skeletal growth, whereas androgens are considered to be a key regulator of male periosteal bone expansion. Moreover, both androgens and GH are essential for the increase in muscle mass during male puberty. Deficiency or resistance to either GH or androgens impairs bone modeling and decreases muscle mass. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/insulin-like growth factor (IGF)-I axis. MATERIALS AND METHODS: Dihydrotestosterone (DHT) or testosterone (T) were administered to orchidectomized (ORX) male GH receptor gene knockout (GHRKO) and corresponding wildtype (WT) mice during late puberty (6-10 weeks of age). Trabecular and cortical bone modeling, cortical strength, body composition, IGF-I in serum, and its expression in liver, muscle, and bone were studied by histomorphometry, pQCT, DXA, radioimmunoassay and RT-PCR, respectively. RESULTS: GH receptor (GHR) inactivation and low serum IGF-I did not affect trabecular bone modeling, because trabecular BMD, bone volume, number, width, and bone turnover were similar in GHRKO and WT mice. The normal trabecular phenotype in GHRKO mice was paralleled by a normal expression of skeletal IGF-I mRNA. ORX decreased trabecular bone volume significantly and to a similar extent in GHRKO and WT mice, whereas DHT and T administration fully prevented trabecular bone loss. Moreover, DHT and T stimulated periosteal bone formation, not only in WT (+100% and +100%, respectively, versus ORX + vehicle [V]; p < 0.05), but also in GHRKO mice (+58% and +89%, respectively, versus ORX + V; p < 0.05), initially characterized by very low periosteal growth. This stimulatory action on periosteal bone resulted in an increase in cortical thickness and occurred without any treatment effect on serum IGF-I or skeletal IGF-I expression. GHRKO mice also had reduced lean body mass and quadriceps muscle weight, along with significantly decreased IGF-I mRNA expression in quadriceps muscle. DHT and T equally stimulated muscle mass in GHRKO and WT mice, without any effect on muscle IGF-I expression. CONCLUSIONS: Androgens stimulate trabecular and cortical bone modeling and increase muscle weight independently from either systemic or local IGF-I production. GHR activation seems to be the main determinant of radial bone expansion, although GHR signaling and androgens are both necessary for optimal stimulation of periosteal growth during puberty.
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