PubMed Health⌕ Search

Biomedical subjects

S Edén

Publications and source records attributed to S Edén.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Additive effects of growth hormone and testosterone on lipolysis in adipocytes of hypophysectomized rats.

The effects of growth hormone (GH) and testosterone, alone or in combination, on the regulation of lipolysis in isolated adipocytes from hypophysectomized rats were investigated. Male Sprague-Dawley rats were hypophysectomized at 50 days of age. One week after operation, hormonal replacement therapy with L-thyroxine and hydrocortisone acetate was given to hypophysectomized rats. Groups of rats were treated with GH (1.33 mg/kg, daily), testosterone (10 mg/kg, once) alone or in combination. After one week of hormonal treatment, adipocytes were isolated from the pooled epididymal and perirenal fat pads and glycerol release after isoproterenol stimulation and 125I-cyanopindolol binding was measured. Hypophysectomy caused a marked decrease in basal and isoproterenol-stimulated lipolysis. There was no effect of testosterone treatment alone on lipolysis, but GH treatment resulted in an increase in isoproterenol-induced lipolysis but not to the levels observed in cells from control rats. Testosterone and GH in combination restored the lipolytic response to isoproterenol. Also 125I-cyanopindolol binding was decreased after hypophysectomy. Testosterone treatment alone and GH treatment alone increased the binding, while in combination the treatment had an additive effect. Affinity was not changed, but the effects seemed to be on receptor number, as determined by Scatchard analysis. Forskolin-stimulated cAMP accumulation in adipocytes was markedly reduced after hypophysectomy. Testosterone treatment alone had no effect. GH treatment alone increased forskolin-stimulated cAMP accumulation, although the level was lower than that found in control rats. The combined treatment resulted in a further increase to levels observed in adipocytes from control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1995

Prevalence of serum antithyroid peroxidase antibodies in 85-year-old women and men.

Antithyroid peroxidase antibodies (TPOAb) were determined by competitive radioassay in serum samples obtained from a representative population of 85-year-olds (601 women and 285 men). The prevalence of increased TPOAb concentration was significantly higher in the women. In individuals without previously known thyroid dysfunction, 16% of the women and 9% of the men had TPOAb concentration > 100 kilo-units/L, the upper decision limit. We found a direct relationship between TPOAb and thyrotropin (TSH) concentrations and an inverse relationship between TPOAb and free thyroxine (T4) concentrations, but no relationship between TPOAb and defined disorders or treatment with pharmaceutical drugs. Exclusion of individuals with increased TPOAb concentration and conditions influencing TSH and free T4 concentrations resulted in a decrease of the upper reference limit for TSH concentration and an increase of the lower limit for free T4 concentration, indicating that high TPOAb concentration should be taken into account when evaluating normal reference intervals for thyroid-function tests in the elderly.

Aged↗
PubMed1994

Reduced hepatic growth hormone (GH) receptor gene expression and increased plasma GH binding protein in experimental uremia.

In uremia, reduced longitudinal growth and decreased hepatic insulin-like growth factor-I (IGF-I) secretion despite elevated GH serum levels point to an insensitivity to the action of GH. The molecular basis that accounts for this insensitivity could comprise decreased GH receptor expression in the target organs for GH or binding of GH in the circulation to substances that compete with the receptor. To address this hypothesis, the abundance of hepatic GH receptor mRNA was measured by solution hybridization RNase protection assay in uremic female Sprague-Dawley rats, following two-stage 5/6 nephrectomy, and in pair-fed and in ad libitum-fed sham-operated controls; rat GH binding protein (GHBP) plasma concentration was measured by a sensitive direct RIA. Uremia was associated with a 50% decrease of hepatic GH receptor expression compared to pair-fed controls, which themselves showed a 25% reduction of hepatic GH receptor mRNA abundance when compared to ad libitum-fed controls. Plasma GHBP levels in uremia were markedly higher than in both control groups. Treatment with recombinant human GH (rhGH) (10 IU/kg body wt per day s.c. for 10 days) led to a comparable induction of IGF-I plasma levels and weight gain in uremia and pair-fed controls, indicating that the insensitivity to GH in uremia can be overcome by large rhGH doses. Subcutaneous rhGH injections did not significantly alter the hepatic GH receptor transcript abundance or plasma GHBP levels in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Low dose continuously infused growth hormone results in increased lipoprotein(a) and decreased low density lipoprotein cholesterol concentrations in middle-aged men.

OBJECTIVE: Animal studies have shown that slight increases in basal GH concentrations may result in changes in lipoprotein metabolism. Such changes in GH secretion have been observed in physiological and pathophysiological states such as fasting, uncontrolled diabetes and during oestrogen treatment. The aim of this study was to investigate the possible effects of increases in basal plasma GH concentrations on lipoprotein concentrations. DESIGNS: Recombinant human growth hormone (rhGH) was given as a continuous subcutaneous infusion in a low dose (0.02 U/kg/day) 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 over a period of 14 days. MEASUREMENTS: Blood samples were obtained after an over-night fast before and after 2, 7 and 14 days of treatment. Plasma and serum were separated and used for subsequent measurements of hormone and lipoprotein concentrations. On days 0, 7 and 14 of treatment, post-heparin plasma was also obtained for determinations of plasma lipoprotein lipase and hepatic lipase activities. In addition, a hyperinsulinaemic euglycaemic glucose clamp was performed on days 0 and 13 of the study. Fat biopsies from abdominal and gluteal fat depots were obtained for measurement of lipoprotein lipase activities on days 0 and 14 of the study. RESULTS: Serum GH concentrations increased to a steady level of 2-4 mU/l during treatment. Serum insulin-like growth factor-I (IGF-I) concentrations increased throughout the treatment period to twice the pretreatment levels. Plasma insulin and blood glucose concentrations increased on day 2 of treatment. After 7 and 14 days of treatment blood glucose concentrations were not different from pretreatment levels, but plasma insulin concentrations were still elevated. Serum cholesterol and low density lipoprotein (LDL) cholesterol concentrations had decreased after 7 and 14 days of treatment. High density lipoprotein (HDL) cholesterol concentrations were not affected, but very low density lipoprotein (VLDL) cholesterol and triglyceride concentrations increased transiently at day 2 of treatment. Serum apolipoprotein (apo) A-I, apoB and apoE concentrations were not significantly affected. Serum lipoprotein(a) concentrations had increased by days 7 and 14 to 147 and 142% of pretreatment concentrations, respectively. Lipoprotein lipase and hepatic lipase activities in post-heparin plasma, as well as abdominal and gluteal adipose tissue lipoprotein lipase activities, were not affected. There was no significant change in glucose disposal rate estimated from the glucose clamp studies. CONCLUSIONS: A low dose infusion of GH results in marked changes in lipoprotein concentrations with a transient increase in VLDL cholesterol and thereafter in a decrease in LDL cholesterol. In addition, this low dose of GH resulted in marked increases in lipoprotein(a) concentrations. The observed effects of GH may partly involve changes in IGF-I and insulin secretion.

Adult↗
PubMed1994

Cardiovascular and renal effects of growth hormone.

OBJECTIVE: With the advent of recombinant human GH (rhGH), it has become possible in controlled clinical studies to explore the effects of GH replacement in adults with GH deficiency. The objective of this study was to determine cardiovascular and renal effects of GH replacement in adults with GH deficiency. PATIENTS: We studied ten patients (one woman and nine men), mean age 47 years, with GH deficiency. DESIGN: The patients were given s.c. rhGH (Humatrope, Eli Lilly) 0.5 U/kg/week or placebo in a 6-month double blind cross-over study. Cardiac and renal function was measured before drug administration (baseline), before cross-over (i.e. after 6 months), and before termination of drug administration (after another 6 months). Analysis of variance was used to compare measurements during GH replacement with baseline and placebo measurements. One patient was excluded because of atrial fibrillation. MEASUREMENTS: Main outcome measures were glomerular filtration rate and Doppler-echocardiographic estimates of cardiac function and structure. Computerized exercise electrocardiogram, spirometry, and blood samples for analyses of plasma hormones were also obtained. RESULTS: Left ventricular function was maintained during GH replacement. However, left ventricular mass increased from 211 to 249 g (P < 0.05) mainly due to increased left ventricular dimension since wall thicknesses did not increase. The left atrium increased from 38 to 41 mm (P < 0.05), possibly because stroke volume increased from 92 to 118 ml (P < 0.0001) and cardiac output increased from 5.29 to 7.58 l/min (P < 0.05). Total peripheral resistance decreased from 18.9 to 12.4 mmHg min/l (P < 0.05), and diastolic blood pressure from 79 to 72 mmHg (P < 0.05). Heart rate at rest increased from 58 to 70 beats/min. Systolic blood pressure at rest was unchanged, as was systolic blood pressure during dynamic exercise. GH replacement did not cause ST-abnormalities. Serum creatinine decreased from 91.4 to 85.3 mumol/l (P < 0.05) and glomerular filtration rate increased from 89.6 to 99.8 ml/min (P < 0.01). CONCLUSIONS: Thus, GH replacement has favourable cardiovascular and renal effects including increase of stroke volume and glomerular filtration rate with reduction of peripheral resistance.

Adult↗
PubMed1994

Endotoxin levels in sera of elderly individuals.

The endotoxin levels in serum of 377 72-year-old individuals were quantitated. The study population was a representative sample of this age group and was participating in a general study of health and disease among the elderly in Göteborg, Sweden. The endotoxin levels in serum were quantified by the chromogenic Limulus amebocyte lysate assay and were correlated with the health status and laboratory findings for each individual. The mean endotoxin levels (+/- 1 standard deviation) in men and women, when excluding four outliers, were 6.6 +/- 3.8 and 6.9 +/- 3.8 pg/ml, respectively. All included, 21.5% of individuals had endotoxin levels equal to or above the sensitivity limit of 10 pg/ml. Strong positive correlations were found between endotoxin levels and plasma triglycerides (P > 0.995) and between endotoxin levels and serum protein (P > 0.9875). The endotoxin activity also correlated with mean corpuscular hemoglobin concentration (P < 0.005, negative correlation), body mass index (P > 0.9875), and decreased appetite (P > 0.9875). A high alcohol consumption was associated with increased endotoxin levels (P = 0.995). There are no previous studies which examine endotoxin levels in serum samples from individuals representative of the population. This study showed that elderly individuals had the same mean level of endotoxin as has been found in other age groups. The increased endotoxin levels seen in heavy drinkers may be explained by a decreased ability of the liver to remove endotoxin. The correlations found between endotoxin and triglycerides, protein, mean corpuscular hemoglobin concentration, decreased appetite, and body mass index are discussed.

Aged↗
PubMed1994

Continuous but not intermittent administration of growth hormone to hypophysectomized rats increases apolipoprotein-E secretion from cultured hepatocytes.

Hypophysectomy of female rats has been shown to decrease the serum levels of apolipoprotein E (apoE). Continuous but not intermittent administration of GH to hypophysectomized (HX) rats increases these levels to those of normal rats, indicating that the sexually dimorphic secretion of GH is important in the regulation of apoE metabolism. In this study, these effects of GH were further investigated by studying the biosynthesis and secretion of apoE from isolated hepatocytes. Hepatocytes were isolated from HX rats as well as from HX rats that had received hormonal treatment with T4 and cortisol (C) or T4 and C together with GH given either as two daily sc injections (GH x 2) or as a continuous infusion (GHc). Hypophysectomy decreased by 47% the amount of apoE present in the culture medium after a 4-h incubation. Treatment of HX rats with T4 and C alone or in combination with GH x 2 did not influence the amount apoE present in the medium, whereas treatment with T4, C, and GHc increased the amount of apoE to that of normal controls. The different levels of apoE in the medium was not due to differences in the disappearance of apoE, indicating that it was caused by changes in the rate of apoE secretion. Consistent with this, hypophysectomy decreased the rate of intracellular accumulation of apoE measured by incubation of the cells with [35S]methionine for 0, 8, and 20 min. Treatment with T4, C, and GHc increased the rate of accumulation, but T4, C, and GH x 2 had no effect. The differences in the initial rate of intracellular accumulation of apoE were not due to variations in apoE messenger RNA pools or to differences in the degradation of apoE at a step early in the secretory pathway. These results indicate that the differences in the initial rate of accumulation of apoE results from differences in the translational rate. The major amount of apoE that was secreted to the medium appeared in the high-density lipoprotein fraction, whereas small amounts were present in the very-low-density lipoprotein fraction (VLDL). Hypophysectomy decreased the amount of newly secreted apoE in the VLDL fraction. Only therapy with T4, C, and GHc could restore the normal distribution of apoE in the VLDL fraction. In conclusion, the results indicate that the secretory pattern of GH is involved in the regulation of the apoE secretion by influencing the rate of translation.

Animals↗