| 121. |
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| 122. |
- Svensson, Johan, 1964, et al.
(author)
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Effects of growth hormone and its secretagogues on bone.
- 2001
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In: Endocrine. - 0969-711X. ; 14:1, s. 63-6
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Journal article (peer-reviewed)abstract
- The growth hormone (GH)/insulin-like growth factor-1 axis is not only of importance for linear body growth during childhood, but it is also one of the major determinants of adult bone mass. Studies show that GH treatment increases bone mass in rodents as well as in adult GH-deficient humans, but the effect of GH treatment on bone mass in healthy humans has so far not been impressive. Recently, a new class of GH secretagogues (GHSs) has been developed. In humans, GHS treatment affects biochemical markers of bone turnover and increases growth velocity in selected short children with or without GH deficiency. In rodents, GHS treatment increase bone mineral content, but it has not yet been shown that GHS treatment can affect bone mass in adult humans.
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| 123. |
- Svensson, Johan, 1964, et al.
(author)
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Effects of seven years of GH-replacement therapy on insulin sensitivity in GH-deficient adults.
- 2002
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In: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 87:5, s. 2121-7
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Journal article (peer-reviewed)abstract
- The few trials in GH-deficient (GHD) adults that have investigated the long-term effects of GH-replacement therapy on insulin sensitivity have shown conflicting results. In this study, insulin sensitivity was determined using the hyperinsulinemic, euglycemic clamp technique in 11 GHD adults at baseline and after 6 months, 1 yr, 2 yr, and 7 yr of GH-replacement therapy. Furthermore, insulin sensitivity in the GHD patients was compared with that in 11 matched control subjects at baseline and with that in 11 other matched controls at study end. The mean initial GH dose was 1.10 mg/d. The dose was gradually lowered; and after 7 yr, the mean dose was 0.61 mg/d. A sustained reduction in body fat and a sustained increase in fat-free mass were observed. Serum high-density lipoprotein-cholesterol (HDL-C) increased, and serum low-density lipoprotein-cholesterol (LDL-C) decreased, after 7 yr of treatment. Fasting blood glucose was transiently increased during the first year of GH replacement. The glucose infusion rate/body weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp technique, was unaltered during GH-replacement therapy. The comparisons with the control subjects revealed that GIR/BW in the GHD patients was 45% of that in the control subjects at baseline; whereas, at study end, the GIR/BW was 71% of that in the control subjects (P = 0.06 vs. baseline). This could suggest that GH-replacement therapy may prevent the age-related decline in insulin sensitivity in GHD patients.
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| 124. |
- Svensson, Johan, 1964, et al.
(author)
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Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice.
- 2006
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In: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 189:3, s. 617-27
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Journal article (peer-reviewed)abstract
- IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer's disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I(-/-)), resulting in an approximately 80-85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I(-/-) and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I(-/-) mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF(-/-) mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I(-/-) mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I(-/-) mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.
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| 125. |
- Svensson, Johan, 1964, et al.
(author)
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GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood.
- 2006
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In: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643. ; 155:1, s. 91-9
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Some adolescents who discontinue GH treatment due to GH deficiency (GHD) and short stature in childhood do not have classical GHD at retesting in adult life. It is unknown whether there is a neuroendocrine disturbance in the spontaneous pattern of GH release in these patients. DESIGN/PATIENTS/METHODS: Thirty-seven adolescents, who had received treatment with GH due to impaired longitudinal growth, were included. The adolescents were divided into two groups; one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24-h GH profiles were performed with blood sampling every 30 min. Sixteen matched healthy controls were also studied. All blood samples were analysed using an ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution analysis were performed. RESULTS: The GHD group had higher mean ApEn level than the healthy controls (P < 0.05). As measured by deconvolution analysis, they had lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001), but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P < 0.001) and lower total GH secretion (P < 0.001), compared with control subjects. Adolescents in the GHS group had a pattern of 24-h GH release similar to that in healthy controls. CONCLUSION: Young adults with childhood-onset severe GHD have a high-frequency, low-amplitude GH secretion with decreased orderliness. The adolescents without classical GHD in adult life maintain a pattern of spontaneous GH release that is not statistically different from that in the healthy controls.
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| 126. |
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| 127. |
- Svensson, Johan, 1964, et al.
(author)
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Growth hormone and the cardiovascular function.
- 2005
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In: Minerva endocrinologica. - 0391-1977. ; 30:1, s. 1-13
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Research review (peer-reviewed)abstract
- In this review, the great importance of growth hormone (GH) for the maintenance of cardiac function in adult life is discussed. Physiological effects of GH are discussed as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality. Finally, the effect of GH treatment in heart failure is discussed.
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| 128. |
- Svensson, Johan, 1964, et al.
(author)
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Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one-year metabolic and clinical response.
- 2007
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In: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 17:1, s. 67-76
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: This study investigated whether baseline status could predict the responsiveness to one-year growth hormone (GH) replacement therapy in adult GH deficient (GHD) patients. DESIGN: A total of 380 European patients with adult onset GHD due to non-functioning pituitary adenoma that had been enrolled in Pfizer International Metabolic Database (KIMS), and that had completed one year of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36 (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip ratio, and serum lipid pattern improved. Women received a higher dose of GH than men after one year, and demonstrated similar treatment response. In multiple stepwise forward regression analyses, the one-year changes in QoL-AGHDA score, waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level correlated inversely with the baseline values of the same variable. In addition, the change after one year in QoL-AGHDA score correlated inversely with duration of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL-C) level, and the change in waist:hip ratio correlated inversely, although more weakly, with baseline serum HDL-C level and UK citizenship and positively with baseline waist circumference and the initial GH dose. The change in serum LDL-C level additionally correlated inversely with the mean GH dose and duration of hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status could, with moderate strength, predict the responsiveness in the same variable whereas it could not, or only weakly, predict the response in other variables. Therefore, when the decision to start GH replacement is undertaken, as many outcome variables as possible should be evaluated in order to adequately evaluate the likelihood of clinical benefit. Finally, women have a similar response to GH replacement as men when individualised GH dosing schedules are employed and should therefore be selected for GH therapy to a similar extent.
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| 129. |
- Svensson, Johan, 1964, et al.
(author)
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Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men.
- 2024
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In: Journal of Bone and Mineral Research. - 0884-0431. ; 39:1, s. 50-58
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Journal article (peer-reviewed)abstract
- Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2yr) elderly men (n=1825; mean age 75, range 69-81yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n=479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05-1.24) and hip fractures (n=207; HR 1.18, 95% CI, 1.04-1.33). Also, in men with normal TSH (n=1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04-2.02 and HR 1.51, 95% CI, 1.07-2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.
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| 130. |
- Svensson, Johan, 1964, et al.
(author)
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Increased diet-induced fatty streak formation in female mice with deficiency of liver-derived insulin-like growth factor-I.
- 2016
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In: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 52:3, s. 550-560
-
Journal article (peer-reviewed)abstract
- The role of endocrine IGF-I for atherosclerosis is unclear. We determined the importance of circulating, liver-derived IGF-I for fatty streak formation in mice. Mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by approximately 80%) and control mice received an atherogenic (modified Paigen) diet between 6 and 12months of age. At study end, Oil Red O staining of aortic root cryosections showed increased fatty streak area and lipid deposition in female but not in male LI-IGF-I(-/-) mice compared to controls. Mac-2 staining of aortic root and measurements of CD68 mRNA level in femoral artery revealed increased macrophage accumulation in proportion to the increased fatty streak area in female LI-IGF-I(-/-) mice. Moreover, female LI-IGF-I(-/-) mice displayed increased serum cholesterol and interleukin-6 as well as increased vascular cell-adhesion molecule 1 (VCAM1) mRNA levels in the femoral artery and elevated VCAM1 protein expression in the aortic root. Thus, increased diet-induced fatty streak formation in female LI-IGF-I(-/-) mice was associated with increased serum cholesterol and signs of systemic inflammation, endothelial activation, lipid deposition, and macrophage infiltration in the vascular wall.
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