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Biomedical subjects

S Edén

Publications and source records attributed to S Edén.

At least 19 recordsLinked to original sources
PubMed2002

Central and peripheral glucocorticoid receptor function in abdominal obesity.

Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.

Abdomen↗
PubMed2001

Pulsatile growth hormone secretion decreases S-adenosylmethionine synthetase in rat liver.

S-adenosylmethionine synthetase (AdoMet synthetase) is responsible for the synthesis of the major methyl donor S-adenosylmethionine. The AdoMet synthetase gene was identified by subtractive suppressive hybridization as being expressed at higher levels in the liver of rats continuously exposed to growth hormone (GH) than in rats intermittently exposed to the hormone. Further studies on the regulation of AdoMet synthetase showed that the activity and mRNA levels were higher in female than in male rats. Hypophysectomy increased AdoMet synthetase mRNA in both male and female rats. Combined thyroxine and cortisol treatment of hypophysectomized rats had no effect on AdoMet synthetase mRNA levels. Two daily injections of GH for 7 days, mimicking the male secretory pattern of GH, decreased AdoMet synthetase activity and mRNA levels. A continuous infusion of GH, mimicking the female secretory pattern of GH, had small or no effects on AdoMet synthetase activity and decreased the mRNA levels to a lesser degree than two daily injections. It is concluded that the lower AdoMet synthetase activity in male rats is due to an inhibitory effect of the male characteristic pulsatile secretory pattern of GH on AdoMet synthetase mRNA expression.

Animals↗
PubMed2001

Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice.

The effects of long-term chronic growth hormone (GH) excess on lipid and lipoprotein metabolism were investigated in 8-mo-old bovine GH (bGH)-transgenic mice. Total body weight, serum cholesterol, insulin-like growth factor-I, and insulin levels were higher, whereas serum levels of glucose, free fatty acids, and triglycerides were lower in transgenic mice. Very low-density lipoprotein (VLDL) cholesterol levels were lower, and low-density lipoprotein (LDL) cholesterol levels were higher, in transgenic mice irrespective of gender, whereas only transgenic male mice had higher high-density lipoprotein cholesterol levels. Total serum apolipoprotein B (apoB) levels were not affected, but the amount of apoB in the LDL fraction was higher in transgenic mice. Hepatic LDL receptor expression was unchanged, whereas apoB mRNA editing and hepatic triglyceride secretion rate were reduced in bGH-transgenic male mice. Both lipoprotein lipase activity in adipose and heart tissue and beta-adrenergic-stimulated lipolysis were increased in transgenic male mice. The relative weight of adipose tissue was lower in transgenic mice, whereas hepatic triglyceride content was unchanged. Fat feeding of the mice equalized serum triglycerides and free fatty acids in bGH-transgenic and control mice. In summary, long-term GH excess is associated with marked alterations in lipid and lipoprotein metabolism, indicating decreased production and increased degradation of VLDL and preferential flux of fatty acids to muscle tissues.

Animals↗
PubMed2000

Different effects of IGF-I on insulin-stimulated glucose uptake in adipose tissue and skeletal muscle.

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.

Adipocytes↗
PubMed2000

Effects of cortisol and growth hormone on lipolysis in human adipose tissue.

The in vitro effects of cortisol and GH on basal and stimulated lipolysis in human adipose tissue were studied using a tissue incubation technique. After preincubation for 3 days in control medium containing insulin, adipose tissue pieces were exposed to cortisol for 3 days. GH was added to the cortisol-containing medium during the last 24 h (day 6). Adipocytes were then isolated, and lipolysis was studied in the absence and presence of isoprenaline, noradrenaline, forskolin, and N-6-monobutyryl-cAMP. Cortisol reduced the basal rate of lipolysis (P < 0.01) and the sensitivity to isoprenaline compared to the control values (P < 0.01). Addition of GH to the cortisol-containing medium increased the basal rate of lipolysis (P < 0.01) and the sensitivity to isoprenaline (P < 0.01) to the control level and increased the maximum isoprenaline-induced lipolytic activity (P < 0.01). Similar effects were obtained in the presence of noradrenaline. Maximum forskolin-induced lipolytic activity was reduced after exposure of the tissue to cortisol (P < 0.05), whereas addition of GH antagonized this effect (P < 0.01). Induction of the maximum lipolytic activity with N-6-monobutyryl-cAMP was not influenced by the preceding hormone exposure. Addition of GH alone during the last 24 h of incubation increased the basal rate of lipolysis (P < 0.05) and resulted in a borderline significant increase in the maximum isoprenaline-induced lipolytic activity (P = 0.055), suggesting that GH induces lipolysis also in the absence of glucocorticoids. Thus, cortisol and GH have opposite effects on the basal lipolytic activity in human adipose tissue in vitro as well as on the sensitivity to catecholamines, GH being the lipolytic and cortisol the antilipolytic agent. The present findings are in agreement with in vivo observations.

Adipose Tissue↗
PubMed1999

GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle tissues of hypophysectomised rats.

Changes in GH secretion are associated with changes in serum lipoproteins, utilisation of fuels and body composition. Since lipoprotein lipase (LPL) is a key enzyme in the regulation of lipid and lipoprotein metabolism, changes in LPL activity may contribute to these effects of GH. The present study was undertaken to investigate the role of GH and the GH-dependent growth factor, IGF-I, in the regulation of LPL in heart, skeletal muscle and adipose tissue. Female rats were hypophysectomised at 50 days of age. One week later, hormonal therapy was commenced. All hypophysectomised rats received l-thyroxine and cortisol. Adipose tissue, the heart, soleus and gastrocnemius muscles were excised after 1 week of hormonal therapy. The effect of insulin injections on adipose tissue and heart LPL activity was also studied. In separate experiments, LPL activity in post-heparin plasma was measured. Hypophysectomy had no effect on adipose tissue LPL activity, whereas activity was reduced in heart, soleus and gastrocnemius muscle tissues. GH treatment had no significant effect on LPL activity in adipose tissue or soleus muscle, but increased the LPL activity in heart and gastrocnemius muscle. GH treatment increased post-heparin plasma LPL activity. Recombinant human IGF-I treatment (1.25 mg/kg per day) markedly reduced LPL activity in adipose tissue, but had no effect in muscle tissues. The effect of IGF-I treatment on adipose tissue LPL was not reflected by a decrease in post-heparin plasma LPL activity. Daily injections of insulin for 7 days increased LPL activity in adipose tissue but had no effect on heart LPL activity. In adipose tissue, LPL mRNA levels tended to decrease as a result of IGF-I treatment. In the muscle tissues, no significant effects of hypophysectomy, GH or IGF-I treatment on LPL mRNA levels were observed.%It is concluded that GH increases heart and skeletal muscle tissue LPL activity, which probably contributes to an increased post-heparin plasma LPL activity. The effect of GH on muscle LPL activity is probably not mediated by IGF-I or insulin. Insulin and IGF-I have opposite effects on LPL activity in adipose tissue.

Adipose Tissue↗
PubMed1999

Effects of growth hormone on lipoprotein lipase and hepatic lipase.

Lipoprotein lipase (LPL) is a key enzyme in the regulation of the flux of fatty acids. LPL hydrolyses triglycerides in chylomicrons and very-low-density lipoproteins (VLDL), forming intermediate- (IDL) and low-density lipoproteins (LDL). Hepatic lipase (HL) is a related enzyme with a more restricted tissue distribution than LPL; HL is mainly engaged in the turnover of IDL and of high-density lipoproteins (HDL). Both enzymes can be released from their endothelial sites by heparin and their activities measured separately in post-heparin plasma (PHP). The PHP-LPL activity decreases in hypophysectomized rats and this effect is reversed by growth hormone (GH) therapy. However, GH seems to have no effect, or an inhibitory effect, on PHP-LPL activity in humans. Muscle and adipose tissues are the main sources of PHP-LPL activity. One week of GH therapy of hypophysectomized rats increases skeletal muscle and heart LPL activity. In this model, GH has little or no effect on LPL activity in adipose tissue. However, GH has been shown to decrease LPL activity in isolated rat adipose tissue. Insulin-like growth factor-I therapy decreases and insulin therapy increases LPL activity in adipose tissue of hypophysectomized rats, whereas these therapies have no effect on LPL activity in muscle tissue. The LPL activity in human adipose tissue is reduced both in vivo and in vitro after administration of GH while the LPL mRNA level is unchanged. The effect of GH on HL activity has been studied in PHP and liver. Several studies in the rat indicate that GH increases PHP-HL and liver HL activity, at least partly at the level of mRNA expression. In humans, GH has been shown to have variable effects on PHP-HL activity; this variability is probably to some extent dependent on different experimental set-ups. Although GH therapy increases hepatic secretion of VLDL, serum triglyceride levels decrease as a result of GH therapy in the hypophysectomized rat. An increase in HL and LPL activity by GH therapy is in line with these findings. In summary, GH is involved in the regulation of both LPL and HL activity but the effects and mechanisms of action of GH in the regulation of LPL and HL activity in different tissues are not yet fully elucidated.

Adipose Tissue↗
PubMed1998

Serum level of placental growth hormone is raised in pregnancy rhinitis.

OBJECTIVE: To describe any relationship between pregnancy rhinitis and weight gain or serum levels of estradiol, progesterone, placental growth hormone, or insulinlike growth factor I. PATIENTS: Twenty-seven nonsmoking healthy pregnant women aged 22 to 38 years (mean age, 28 years) who had no history of respiratory allergy or chronic nasal or sinus problems volunteered to enter the study. They had no nasal complaints at entry. METHODS: Nasal patency was registered daily from early pregnancy until 1 month after delivery. Nasal and oral peak expiratory flow rates were established, and the subjective blockage was scored from 0 to 4, with 0 indicating no blockage. Serum samples were collected and weight was measured on 4 occasions during pregnancy and again at the end of the study. Pregnancy rhinitis was diagnosed if the subjective nasal obstruction score was 1 or higher every morning for at least 6 weeks immediately preceding delivery, then returned to 0 within 2 weeks and remained at 0 until the end of the study. If on any day other signs of respiratory tract infection occurred, that day was excluded. RESULTS: Pregnancy rhinitis was diagnosed in 5 women. These 5 women showed significantly higher levels of placental growth hormone than the women without the diagnosis. No significant difference was found between the 2 groups regarding body weight or any of the other serum levels studied. CONCLUSIONS: Serum level of placental growth hormone is raised in pregnancy rhinitis and may be involved in its pathogeny. Pregnancy rhinitis does not significantly raise weight gain or serum levels of estradiol, progesterone, or insulinlike growth factor I.

Adult↗
PubMed1996

Growth hormone treatment of hypophysectomized rats increases catecholamine-induced lipolysis and the number of beta-adrenergic receptors in adipocytes: no differences in the effects of growth hormone on different fat depots.

Growth hormone (GH) has a lipolytic effect in adipose tissue but this effect may differ in adipose tissue from various fat depots. This latter possibility was investigated in the present study, in which the effects of GH in vivo on catecholamine-induced lipolysis and the number of beta-adrenergic receptors in isolated adipocytes from different fat depots of hypophysectomized rats were investigated. Female and male Sprague-Dawley rats were hypophysectomized or sham-operated at 45 days of age. One week after the operation, hormonal replacement therapy with L-thyroxine and hydrocortisone acetate was given. In addition, groups of rats were treated with GH (1.33 mg/kg per day, given as two daily subcutaneous injections). After 1 week of hormonal treatment, adipocytes were isolated from the parametrial, epididymal and inguinal fat pads, and glycerol release after catecholamine-stimulation and 125I-cyanopindolol binding were measured. Hypophysectomy resulted in a marked decrease in the lipolytic response to catecholamines. GH treatment significantly increased catecholamine-induced lipolysis with similar effects in adipocytes from parametrial or epididymal and inguinal fat depots in both female and male rats. There were no differences between norepinephrine compared with isoproterenol-induced responses. 125I-cyanopindolol binding was reduced after hypophysectomy and normalized by GH treatment, without differences between parametrial and inguinal adipose tissue regions. We conclude that the lipolytic effects of GH in the rat may partly be mediated by a stimulatory effect on beta-adrenergic receptors in adipocytes. In addition, GH exerted similar effect on catecholamine induced lipolysis and beta-adrenergic receptors in adipocytes from parametrial, epididymal and inguinal fat depots.

Adipocytes↗
PubMed1996

The effect of growth hormone on low-density lipoprotein cholesterol and lipoprotein (a) levels in familial hypercholesterolemia.

Severe elevations of low-density lipoprotein (LDL) cholesterol are not always normalized with conventional drugs. Growth hormone decreases LDL cholesterol levels, in part by augmenting liver LDL receptor activity. This increase may be on the order of magnitude of the increase induced by statins. We investigated the effect of growth hormone in familial hypercholesterolemia (FH) in a randomized, double-blind, placebo-controlled study. Thirty-one men with FH aged 20 to 48 years, of whom 81% had a known LDL receptor gene mutation, discontinued all lipid-lowering drugs 6 weeks before the study. Dietary stabilization continued for 5 more weeks, followed by single-blind placebo injections for 1 week. Thereafter, 16 subjects were allocated to recombinant growth hormone 0.05 IU/kg/d and 15 to placebo injected subcutaneously for 12 weeks. Baseline lipid levels were similar in both groups. One subject in the growth hormone group withdrew after 8 weeks due to shoulder pain. Mean compliance among the rest of the subjects was 98%. The mean change in LDL cholesterol was -0.46 mmol/L (95% confidence interval [CI], -1.00 to 0.09 mmol/L) in the growth hormone group versus 0.08 mmol/L (95% CI, -0.55 to 0.71 mmol/L) in the placebo group (difference not significant). No changes occurred in the levels of other lipids, lipoprotein particles, or apolipoproteins, with the exception of lipoprotein(a) [Lp(a)]. The median changes in Lp(a) were 33% (interquartile range, 2% to 53%) and -15% (interquartile range, -22% to 18%) in the growth hormone and placebo groups, respectively (P = .02). We conclude that the effect of growth hormone on LDL cholesterol levels in FH is less than expected, based on its LDL-catabolic effects, and is counteracted by profound increases in Lp(a) levels, resulting in unchanged levels of apolipoprotein B. Thus, growth hormone is probably not useful as adjunctive therapy in FH.

Adult↗
PubMed1996

Continuous subcutaneous infusion of low dose growth hormone decreases serum sex-hormone binding globulin and testosterone concentrations in moderately obese middle-aged men.

OBJECTIVE: Sex-hormone binding globulin (SHBG) is a liver derived protein whose concentration has been shown to be affected by a number of factors. The aim of the present study was to investigate the possible effect of increased basal GH concentrations on serum concentrations of SHBG, testosterone and thyroid hormones. DESIGNS: Recombinant human growth hormone (rhGH) was given as a continuous subcutaneous infusion in a low dose (0.02 U/kg/day) over a period of 14 days in an open study. PATIENTS: Eight middle-aged (42-59 years) overweight (body mass index 26.1-33.8 kg/m2) but otherwise healthy men were studied. MEASUREMENTS: Blood samples were obtained after an over-night fast before and after 2, 7 and 14 days of treatment. Serum was separated and stored at -20 degrees C until assay. RESULTS: Serum GH concentrations increased to a steady level of 2-4 mU/l. Serum SHBG concentration decreased between 2 and 7 days of treatment and serum testosterone concentration changed in parallel. There was no change in the ratio between serum SHBG and serum testosterone. Serum T4 and free T4 concentrations decreased, and that of T3 increased as a result of continuous GH infusion. Simple correlations between changes in SHBG concentrations and other hormonal changes showed positive significant correlations between changes of SHBG and of testosterone. CONCLUSIONS: Low dose continuously infused GH resulted in a parallel decrease in serum SHBG and testosterone concentrations. Thyroid hormone concentrations were affected in a similar way to that previously demonstrated following daily injections of GH.

Adult↗
PubMed1996

Mode of growth hormone administration influences triacylglycerol synthesis and assembly of apolipoprotein B-containing lipoproteins in cultured rat hepatocytes.

Hypophysectomized female rats were treated for 1 week with thyroxine (10 micrograms/kg.day), cortisol (400 micrograms/kg.day), and bovine GH (1 mg/kg.day) either as two daily subcutaneous injections (GH x 2) or as a continuous subcutaneous infusion (GHc) in order to mimic the male and female specific GH secretory patterns, respectively. Hepatocytes were then isolated and kept in short-term cultures. Hypophysectomy decreased the synthesis of triacylglycerol. Treatment with GH x 2 had no or small effects, while GHc normalized the effect of hypophysectomy. ApoB-100 VLDL was assembled before apoB-48 VLDL. ApoB-48 was first assembled as an HDL particle (apoB-48 "HDL"). Hypophysectomy decreased the proportion of intracellular apoB-48 that was recovered as VLDL. Moreover, the proportion of apoB-48 of total apoB in VLDL decreased. Only GHc fully restored the effect of hypophysectomy by inducing an 4-fold increase in the assembly of apoB-48 VLDL, while treatment with GH x 2 gave rise to a 1.8-fold increase. Hypophysectomy resulted in a decrease in the proportion of apoB-48 that was secreted as VLDL and a decrease in the proportion of apoB-48 of total apoB in VLDL. Only treatment with GHc fully restored the secretion of apoB-48 VLDL by inducing an almost 4-fold increase in the secretion of apoB-48 VLDL, while the corresponding value for treatment with GH x 2 was 1.7. However, GH x 2 increased the proportion of the secreted apoB-48 that was recovered in VLDL to the levels found in normal rats and in rats treated with GHc, but this finding was due to a failure of GH x 2 treatment to increase the secretion of apoB-48 "HDL". In summary, a continuous infusion of GH to hypophysectomized rats, mimicking the female secretion of GH, normalized the triacylglycerol synthesis and secretion as well as apoB-48 VLDL assembly and secretion to those levels observed in hepatocyte cultures from intact female rats.

Animals↗
PubMed1995

Recombinant human insulin-like growth factor-I decreases serum lipoprotein(a) concentrations in normal adult men.

OBJECTIVE: Lipoprotein(a) is a lipoprotein fraction associated with atherosclerosis. The serum concentration of lipoprotein(a) has been shown to be mainly genetically determined but recently evidence for hormonal regulation has been presented. The aim of the present study was to investigate the effects of insulin-like growth factor-I on serum lipoproteins, especially lipoprotein(a). DESIGN: The effects of one week of IGF-I treatment were studied in an open trial. SUBJECTS: Ten healthy men, who participated in a pharmacokinetic study, were given recombinant human insulin-like growth factor-I (40 micrograms/kg/day) as daily subcutaneous injections. MEASUREMENTS: Serum samples for measurements of lipoproteins were taken after an overnight fast before and after 7 days of treatment. RESULTS: There was decrease in serum lipoprotein(a) concentration (18.5 +/- 5.5%) in nine of the subjects, and a slight increase in one of the subjects with the lowest concentrations. Also serum apolipoprotein (b) (6.3 +/- 2.2%), serum cholesterol (10.6 +/- 1.8%) and serum triglyceride (14.8 +/- 4.8%) concentrations decreased. An unexpected finding was that fasting serum glucose concentrations increased (13 +/- 4%). CONCLUSION: Insulin-like growth factor-I is involved in the regulation of lipoprotein(a) concentrations, which might have novel therapeutic implications.

Adult↗
PubMed1995

Growth hormone inhibits lipoprotein lipase activity in human adipose tissue.

The in vitro effects of GH on human adipose tissue lipoprotein lipase (LPL) activity and messenger ribonucleic acid (mRNA) levels were studied using a tissue incubation technique. After preincubation for 3 days, abdominal sc adipose tissue pieces were exposed to cortisol (1000 nmol/L) for 3 days to induce LPL activity. Addition of GH (50 micrograms/L) to the cortisol-containing medium during the last 24 h (day 6) caused a decrease by 84 +/- 4% (P < 0.01) in heparin-releasable LPL activity and by 65 +/- 4% (P < 0.01) in total LPL activity. Moreover, the heparin-releasable fraction was reduced from 42% of the total LPL activity with cortisol alone to 17% when both GH and cortisol were present in the incubation medium during the last 24 h (P < 0.01). The reduction in LPL activity in response to GH was not accompanied by a decrease in the level of LPL mRNA measured by a solution hybridization ribonuclease protection assay. In adipose tissue incubated in the control medium for 6 days, the addition of GH alone during the last 24 h caused an insignificant decrease in heparin-releasable LPL activity. Low control activities limited the scope for further decrease. It is concluded that GH counteracts the potent stimulatory effect of glucocorticoids on LPL activity without affecting LPL mRNA levels. Therefore, the inhibition of LPL activity by GH probably occurs during translation and/or posttranslational processing of the enzyme, and the mechanism may involve a decreased channeling of the lipase to the cell surface.

Adipose Tissue↗