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- Abrahamsson, Annelie, et al.
(författare)
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Estradiol, Tamoxifen, and Flaxseed Alter IL-1 beta and IL-1Ra Levels in Normal Human Breast Tissue in Vivo
- 2012
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 97:11, s. E2044-E2054
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression. IL-1Ra is an endogenous inhibitor of the proinflammatory IL-1 alpha and IL-1 beta. less thanbrgreater than less thanbrgreater thanObjective: The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL-1 levels in normal human breast tissue. less thanbrgreater than less thanbrgreater thanDesign and Methods: Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. less thanbrgreater than less thanbrgreater thanResults: We show a significant positive correlation between estradiol and in vivo levels of IL-1 beta in breast tissue and abdominal sc fat, whereas IL-1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL-1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL-1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL-1 beta were significantly higher compared with normal adjacent breast tissue. less thanbrgreater than less thanbrgreater thanConclusion: IL-1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL-1 beta in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.
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| 2. |
- Agnarsson, Hjalmar Ragnar, et al.
(författare)
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The impact of glucocorticoid replacement on bone mineral density in patients with hypopituitarism before and after 2 years of growth hormone replacement therapy.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:4
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have reduced bone mineral density (BMD) and increased fracture risk. Objective: The aim of this study was to analyze the effects of glucocorticoid (GC) replacement on BMD before and after two years of growth hormone (GH) therapy in hypopituitary patients. The main hypothesis was that patients on GC replacement demonstrate greater improvement in BMD when treated with GH. Design: This was a post hoc analysis of data from a prospective single centre study. Patients: Data on 175 adult patients with hypopituitarism and verified GH deficiency due to non-functioning pituitary adenoma were analyzed. Ninety-eight (56%) were GC insufficient, receiving a mean±SD hydrocortisone equivalent dose of 20.9±5.0 mg/day. Main outcome measure: BMD before and after two years of GH replacement therapy, measured by using dual-energy X-ray absorptiometry. Results: BMD at baseline did not differ between GC sufficient and insufficient patients, neither at lumbar spine nor femur neck. After two years on GH replacement BMD increased in both groups. After adjustment for weight, age, gender, free T4 concentrations, change in IGF-I levels and sex hormone treatment, GC sufficiency was associated with greater increase in BMD at femur neck (ΔT-score in GC insufficient patients 0.09±0.46, in GC sufficient patients 0.19±0.43; P<0.05) but not at lumbar spine. Conclusions: GH replacement therapy for 2 years increased BMD in hypopituitary patients. In contrast to our hypothesis, GC insufficient patients receiving near physiological doses of hydrocortisone do not show a greater therapeutic response to GH therapy than their GC sufficient counterparts.
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| 3. |
- Ahmed, Fozia, et al.
(författare)
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Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 107:5, s. E1879-E1889
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Tidskriftsartikel (refereegranskat)abstract
- Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.Results: ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.Conclusion: E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.
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| 8. |
- Ahrén, Bo, et al.
(författare)
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Vildagliptin Enhances Islet Responsiveness to Both Hyper- and Hypoglycemia in Patients with Type 2 Diabetes.
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 1236-1243
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Tidskriftsartikel (refereegranskat)abstract
- Context: Dipeptidyl peptidase-4 (DPP-4) inhibitors act by increasing plasma levels of glucagon-like peptide-1 (GLP-1) and suppressing excessive glucagon secretion in patients with type 2 diabetes (T2DM). However, their effects on the glucagon response to hypoglycemia are not established. Objective: Assess effects of the DPP-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia. Design: Single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout Setting: Participants received study drug as outpatients. Patients: Drug-naïve patients with T2DM and baseline HbA1c
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| 9. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 10. |
- Albertsson-Wikland, Kerstin, et al.
(författare)
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Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics
- 2016
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 101:5, s. 2149-2159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.
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