| 1. |
- Améen, Caroline, 1975, et al.
(författare)
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Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver.
- 2004
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 287:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether the sexually dimorphic secretory pattern of growth hormone (GH) in the rat regulates hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes. SREBP-1c, fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT) mRNA were more abundant in female than in male livers, whereas acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) were similarly expressed in both sexes. Hypophysectomized female rats were given GH as a continuous infusion or as two daily injections for 7 days to mimic the female- and male-specific GH secretory patterns, respectively. The female pattern of GH administration increased the expression of SREBP-1c, ACC1, FAS, SCD-1, and GPAT mRNA, whereas the male pattern of GH administration increased only SCD-1 mRNA. FAS and SCD-1 protein levels were regulated in a similar manner by GH. Incubation of primary rat hepatocytes with GH increased SCD-1 mRNA levels and decreased FAS and GPAT mRNA levels but had no effect on SREBP-1c mRNA. GH decreased hepatic liver X receptor-alpha (LXRalpha) mRNA levels both in vivo and in vitro. Feminization of the GH plasma pattern in male rats by administration of GH as a continuous infusion decreased insulin sensitivity and increased expression of FAS and GPAT mRNA but had no effect on SREBP-1c, ACC1, SCD-1, or LXRalpha mRNA. In conclusion, FAS and GPAT are specifically upregulated by the female secretory pattern of GH. This regulation is not a direct effect of GH on hepatocytes and does not involve changed expression of SREBP-1c or LXRalpha mRNA but is associated with decreased insulin sensitivity.
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| 2. |
- Johansson, Jan-Ove, 1955, et al.
(författare)
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Growth hormone (GH) replacement in GH-deficient adults: a crossover trial comparing the effect on metabolic control, well-being and compliance of three injections per week versus daily injections.
- 2003
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - 1096-6374. ; 13:6, s. 306-15
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) replacement therapy regimens in adults using daily subcutaneous (sc) injections may not be optimal with respect to carbohydrate and lipid metabolism. The aim of this study was to compare the efficacy of three times weekly injections with daily sc GH injections in terms of serum IGF-I, IGFBPs, lipoprotein levels, serum bone markers, glucose metabolism, body composition, compliance and well-being. Twenty hypopituitary men, 46-76 years, on a course of stable conventional GH replacement therapy for more than 12 months, were included in a 16-week crossover trial. During the first 8 weeks GH was administered three times per week followed by 8 weeks with daily sc injections with the same weekly dose of GH. Fasting serum samples were collected at baseline and on two consecutive days at the end of each 8-week period. Serum IGF-I and IGFBP-3 concentrations were lower both the first and second morning after the last injection during the period with three injections per week. The second morning after the last GH injection in this period the IGF-I/BP-3 ratio, plasma insulin and FFA were lower whereas IGFBP-1 was increased as compared with values obtained during the period with daily injections. Serum Lp(a) levels, body composition, fat distribution, well-being and compliance were not differently affected by the two treatment regimens. These results suggest that the same weekly dose of GH given as three injections per week reduces serum IGF-I and IGFBP-3 levels without affecting Lp(a) levels. The day-to-day variation in glucose metabolism and FFA serum levels differs considerably between the two modes of GH administration.
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| 3. |
- Lindén, Daniel, 1971, et al.
(författare)
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Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48.
- 2002
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 277:25, s. 23044-53
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Tidskriftsartikel (refereegranskat)abstract
- The peroxisome proliferator-activated receptor (PPAR) alpha agonist WY 14,643 increased the secretion of apolipoprotein (apo) B-100, but not that of apoB-48, and decreased triglyceride biosynthesis and secretion from primary rat hepatocytes. These effects resulted in decreased secretion of apoB-100-very low density lipoprotein (VLDL) and an increased secretion of apoB-100 on low density lipoproteins/intermediate density lipoproteins. ApoB-48-VLDL was also replaced by more dense particles. The proteasomal inhibitor lactacystin did not influence the recovery of apoB-100 or apoB-48 in primary rat hepatocytes, indicating that co-translational (proteasomal) degradation is of less importance in these cells. Treatment with WY 14,643 made the recovery of apoB-100 sensitive to lactacystin, most likely reflecting the decreased biosynthesis of triglycerides. The PPAR alpha agonist induced a significant increase in the accumulation of pulse-labeled apoB-100 even after a short pulse (2-5 min). There was also an increase in apoB-100 nascent polypeptides, indicating that the co-translational degradation of apoB-100 was inhibited. However, a minor influence on an early posttranslation degradation cannot be excluded. This decreased co-translational degradation of apoB-100 explained the increased secretion of the protein. The levels of apoB-48 remained unchanged during these pulse-chase experiments, and albumin production was not affected, indicating a specific effect of PPAR alpha agonists on the co-translational degradation of apoB-100. These findings explain the difference in the rate of secretion of the two apoB proteins seen after PPAR alpha activation. PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP). Increased expression of LFABP by transfection of McA-RH7777 cells increased the secretion of apoB-100, decreased triglyceride biosynthesis and secretion, and increased PPAR alpha mRNA levels. These findings suggest that PPAR alpha and LFABP could interact to amplify the effect of endogenous PPAR alpha agonists on the assembly of VLDL.
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| 4. |
- Frick, Fredrik, 1973, et al.
(författare)
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Different effects of IGF-I on insulin-stimulated glucose uptake in adipose tissue and skeletal muscle.
- 2000
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Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 278:4
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Tidskriftsartikel (refereegranskat)abstract
- The effect of insulin-like growth factor I (IGF-I) on insulin-stimulated glucose uptake was studied in adipose and muscle tissues of hypophysectomized female rats. IGF-I was given as a subcutaneous infusion via osmotic minipumps for 6 or 20 days. All hypophysectomized rats received L-thyroxine and cortisol replacement therapy. IGF-I treatment increased body weight gain but had no effect on serum glucose or free fatty acid levels. Serum insulin and C-peptide concentrations decreased. Basal and insulin-stimulated glucose incorporation into lipids was reduced in adipose tissue segments and isolated adipocytes from the IGF-I-treated rats. In contrast, insulin treatment of hypophysectomized rats for 7 days increased basal and insulin-stimulated glucose incorporation into lipids in isolated adipocytes. Pretreatment of isolated adipocytes in vitro with IGF-I increased basal and insulin-stimulated glucose incorporation into lipids. These results indicate that the effect of IGF-I on lipogenesis in adipose tissue is not direct but via decreased serum insulin levels, which reduce the capacity of adipocytes to metabolize glucose. Isoproterenol-stimulated lipolysis, but not basal lipolysis, was enhanced in adipocytes from IGF-I-treated animals. In the soleus muscle, the glycogen content and insulin-stimulated glucose incorporation into glycogen were increased in IGF-I-treated rats. In summary, IGF-I has opposite effects on glucose uptake in adipose tissue and skeletal muscle, findings which at least partly explain previous reports of reduced body fat mass, increased body cell mass, and increased insulin responsiveness after IGF-I treatment.
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| 5. |
- Leonsson, Maria, et al.
(författare)
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Intima-media thickness in cardiovascularly asymptomatic hypopituitary adults with growth hormone deficiency: relation to body mass index, gender, and other cardiovascular risk factors.
- 2002
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Ingår i: Clinical endocrinology. - 0300-0664. ; 57:6, s. 751-9
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Tidskriftsartikel (refereegranskat)abstract
- Increased cardiovascular mortality and carotid atherosclerosis have been observed in hypopituitary patients with untreated GH deficiency (GHD), but results are contradictory and relations to cardiovascular risk factors are not clear. The aim of this study was to investigate intima-media thickness (IMT) in relation to cardiovascular risk factors in adults with GHD.Cross-sectional observational study of 21 men and 13 women with GHD, but without cardiovascular disease, compared to two healthy control groups matched for age, sex and smoking habits. One control group was matched for body mass index (BMI) and the other group was nonobese.IMT of the carotid and femoral arteries, blood pressure, blood samples and anthropometric data.Patients had 12% thicker composite carotid IMT [(IMT of common carotid artery + IMT of bulb)/2] compared to nonobese controls (P = 0.022), but IMT was not different compared to BMI-matched controls. Femoral IMT did not differ between patients and controls. Patients had higher waist : hip ratio (WHR), heart rate, serum triglycerides and fasting insulin concentrations in combination with lower high-density lipoprotein (HDL) cholesterol and smaller low-density lipoprotein (LDL) peak particle size compared to both nonobese and to BMI-matched controls. This cardiovascular risk pattern was more pronounced in female patients than in male patients compared to their gender controls. Carotid IMT was related to age, serum cholesterol, LDL cholesterol and smoking in the patient group. Only age was independently related to carotid IMT in multivariate analysis.These results indicate that high BMI in GH-deficient patients contribute to their increased intima-media thickness. However, several cardiovascular risk factors are present in this patient group independent of their increased BMI, especially in women.
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| 6. |
- Persson, Anders I., 1973, et al.
(författare)
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Expression of delta opioid receptor mRNA and protein in the rat cerebral cortex and cerebellum is decreased by growth hormone.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Hormones released from the pituitary have been shown to regulate the expression of different proteins in the central nervous system. We wanted to examine whether peripheral administration of bovine growth hormone (bGH) regulates the expression of delta-opioid receptor (DOR) in the cerebral cortex and cerebellum. Expression of the DOR protein was quantified using Western blot densitometry. DOR mRNA was quantified with a solution hybridization RNase protection assay. Hypophysectomized (Hx) and untreated normal female rats were included in the study. All Hx rats were hormonally treated with cortisol (400 microg/kg/day) and L-thyroxine (10 microg/kg/day) for 19 days. Hypophysectomy resulted in a threefold increase in cerebral cortex and a twofold increase in cerebellum of the DOR protein compared with normal rats. One subgroup of Hx rats received bGH (1 mg/kg body weight) as a daily subcutaneous injection for 19 days. This treatment normalized the levels of DOR protein in the cerebral cortex and cerebellum. Immunohistochemical experiments showed that GH decreased DOR expression especially in layers II-VI in cerebral cortex and in stratum moleculare in cerebellum. Quantification of DOR mRNA by solution hybridization RNase protection assay corresponded to the DOR protein measurements. We conclude that the expression of DORs in cerebral cortex and cerebellum is regulated by GH.
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| 7. |
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| 8. |
- Åberg, Maria A I, 1972, et al.
(författare)
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Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus.
- 2000
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 20:8, s. 2896-903
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Tidskriftsartikel (refereegranskat)abstract
- In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.
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| 9. |
- Åberg, N David, 1970, et al.
(författare)
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Growth hormone increases connexin-43 expression in the cerebral cortex and hypothalamus.
- 2000
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Ingår i: Endocrinology. - 0013-7227. ; 141:10, s. 3879-86
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Tidskriftsartikel (refereegranskat)abstract
- Several studies indicate that systemic GH influences various brain functions. Connexin-43 forms gap junctions that mediate intercellular communication and establish the astroglial syncytium. We investigated the effects of peripheral administration of bovine GH (bGH) and recombinant human insulin-like growth factor I (rhIGF-I) on the expression of connexin-43 in the rat brain. Hypophysectomized female Sprague Dawley rats were substituted with cortisol (400 microg/kg x day) and L-T4 (10 microg/kg x day) and treated with either bGH (1 mg/kg x day) or rhIGF-I (0.85 mg/kg x day) for 19 days. The abundance of connexin-43 messenger RNA (mRNA) and protein in the brainstem, cerebral cortex, hippocampus, and hypothalamus was quantified by means of ribonuclease protection assays and Western blots. Treatment with bGH increased the amounts of connexin-43 mRNA and protein in the cerebral cortex and hypothalamus. No changes were found in the brainstem or hippocampus. Infusion of rhIGF-I did not affect connexin-43 mRNA or protein levels in any of the brain regions studied. These results show that administration of bGH increases the abundance of cx43 in specific brain regions, suggesting that GH may influence gap junction formation and thereby intercellular communication in the brain.
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