RESUMO
Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.
Assuntos
Acromegalia/sangue , Hormônio do Crescimento Humano/deficiência , Hormônios Peptídicos/sangue , Adulto , Antropometria , Estudos de Casos e Controles , Feminino , Grelina , Hormônios/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Somatomedinas/metabolismoRESUMO
Ghrelin was originally isolated from the rat stomach and significant amounts were found also in the kidney. Present study was designed to examine changes in ghrelin levels in renal failure and their relationship to the GH/IGF-I axis. Fourty patients with mild-to-severe CRF (19 men, 21 women, aged 62.5 +/- 2.2 years, BMI 27.57 +/- 0.73 kg/m(2)) and 34 healthy control subjects (17 men, 17 women, aged 60 +/- 2.6 years, BMI 27.55 +/- 0.79 kg/m(2)) were included in the study. Total ghrelin levels were significantly increased in patients with chronic renal failure (CRF) (p < 0.0001). Total ghrelin in CRF correlated positively with active ghrelin (p < 0.001), GH (p < 0.05), IGF-I (p < 0.05), free IGF-I (p = 0.0001), IGFBP-3 (p < 0.01), IGFBP-2 and -6 (p < 0.05). Active ghrelin in CRF correlated positively with IGF-I (p < 0.001), free-IGF-I (p < 0.005), IGFBP-2 (p < 0.05) and IGFBP-3 (p < 0.05). However, most of the correlation were markedly reduced and the significance disappeared after adjustment for different creatinine levels. Hemodialysis in patients with end stage renal disease (ESRD) resulted in a significant reduction of plasma total and active ghrelin (p < 0.01 and p < 0.001 respectively). In conclusion we demonstrated elevated plasma levels of total ghrelin in CRF, and a reduction of total and active ghrelin after a single course of hemodialysis in ESRD. The elevation of ghrelin levels could be caused by impaired clearance and/or metabolism of ghrelin in the kidney. We did not prove clearly significant relationship between ghrelin serum levels and parameters of GH/IGF-I axis in study subjects.
Assuntos
Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Falência Renal Crônica/sangue , Hormônios Peptídicos/sangue , Insuficiência Renal/sangue , Animais , Índice de Massa Corporal , Estudos de Casos e Controles , Creatina/sangue , Feminino , Grelina , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Rim/metabolismo , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Hormônios Peptídicos/química , Hormônios Peptídicos/metabolismo , Receptores de Superfície Celular/química , Receptores para Leptina , Diálise Renal , Fatores de TempoRESUMO
Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.
Assuntos
Falência Renal Crônica/sangue , Hormônios Peptídicos/sangue , Idoso , Composição Corporal/fisiologia , Creatinina/sangue , Feminino , Grelina , Hormônio do Crescimento Humano/metabolismo , Humanos , Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/metabolismo , Receptores para Leptina , Diálise RenalRESUMO
Ghrelin is a peptide hormone that is involved in regulating growth hormone secretion as well as food intake and energy homeostasis. The aim of this study was to compare changes in plasma ghrelin levels in patients with malnutrition due to anorexia nervosa (AN) or short bowel syndrome (SBS). Blood samples for laboratory analyses were taken from 16 AN patients (plus 13 comparable healthy controls) and 27 SBS patients (plus 13 comparable healthy controls) after an overnight fast. In comparison with their respective control groups, plasma ghrelin levels were increased in the AN patients (p < 0.05) and significantly decreased in the patients with SBS (p < 0.01). These results suggest that quantitative ghrelin secretion in the gut wall is important in determining ghrelin concentrations in the systemic circulation.
Assuntos
Anorexia Nervosa/complicações , Desnutrição/sangue , Desnutrição/etiologia , Hormônios Peptídicos/sangue , Síndrome do Intestino Curto/complicações , Tecido Adiposo , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Jejum , Feminino , Grelina , Hormônio do Crescimento/sangue , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Masculino , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Avaliação Nutricional , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/fisiologia , Receptores de Superfície Celular/sangue , Receptores para Leptina , Caracteres Sexuais , Dobras CutâneasRESUMO
UNLABELLED: We present the results of two experiments aimed at the role of IGF-I and NO in the regulation of bone blood flow. In the first experiment A we determined the blood circulation in tibia and distal part of femur and the blood level of IGF-I after oophorectomy (OOX, 4 weeks before the experiment) and/or administration of NG-nitro-L-arginin methyl ester (L-NAME, Sigma, USA, 0.05% in the food for 10 days before the experiment). In the second experiment B we checked up the possibility of correlation between the bone blood flow and IGF-I level in female rats control and after the administration of estradiol (Agofollin Depot, Biotika, Slovak Republic, 1 mg s.c., two times weekly, for 4 weeks before the experiment). The bone blood flow was ascertained by means of 85-Sr microsphere (NEN, USA) technique, IGF level was estimated with Rat IGF-I RIA kit (DSL, USA). RESULTS: Experiment A: group I: controls--sham operation, group II: oophorectomy (OOX), group III: L-NAME + sham operation, group IV: OOX + L-NAME. OOX elevated the 85-Sr microsphere uptake and bone blood flow in tibia and distal femur. The administration of L-NAME to non-castrated females lowered significantly the blood flow in the femur only, whereas in OOX females it inhibited completely the usual OOX-induced increase in circulatory indicators in both bones. IGF-I level was higher after OOX, administration of L-NAME did not exert any effect on it. Experiment B: group I: control females, group II: estradiol. After the administration of estradiol, there was marked decrease in the uptake of 85-Sr microspheres and blood flow in both bones, decrease in body weight, cardiac output, heart rate, blood pressure and also in the blood level of IGF-I. Density and ash weight of the tibia were elevated. Important results found in the group I of experiment B seem to be the correlations between the blood level of IGF-I and 85-Sr microsphere uptake in tibia (r = 0.68, p < 0.01), between IGF-I and blood flow in tibia (r = 0.54, p < 0.05) and between IGF-I and 85-Sr microsphere uptake in distal femur (r = 0.55, p < 0.05). However, in the group II of females after estradiol no significant dependence could be demonstrated. The results support the conception of the role of IGF-I and NO in the regulation of local blood flow also in the bones of rats. The possible sequence of the interrelations could be as follows: OOX--increase in the blood level of IGF-I--increase in the production of NO--vasodilatation and increase in the bone blood flow. Significant correlations between the blood level of IGF-I and bone blood flow represent further evidence of the participation of IGF-I in the regulation of bone blood flow in rats.
Assuntos
Fêmur/irrigação sanguínea , Fator de Crescimento Insulin-Like I/fisiologia , Óxido Nítrico/fisiologia , Tíbia/irrigação sanguínea , Animais , Estradiol/farmacologia , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Ovariectomia , Ratos , Fluxo Sanguíneo Regional , Vasodilatadores/farmacologiaRESUMO
BACKGROUND AND AIM: System of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP) may be involved in the pathogenesis of vascular damage in Type 2 diabetes. Aim of the study was to analyse the relationship between this system and microvascular reactivity in Type 2 diabetes as measured by laser-Doppler flowmetry. METHODS AND RESULTS: Thirteen Type 2 diabetic patients (8 women and 5 men) with microangiopathy and fifteen healthy subjects (8 women and 7 men) were examined clinically, underwent laser-Doppler flowmetry and intima-media thickness measurements. Fasting serum levels of IGF-I, IGFBP and lipids were examined. Percentage perfusion increase in the test with postocclusive reactive hyperaemia (PORH) as well as in that with thermal hyperaemia (TH) were significantly decreased in Type 2 diabetic patients (p < 0.05). Maximal perfusion after heating (THmax) was lower in Type 2 diabetic patients. Reaction of microcirculation after heating (THmax/t) was slower in Type 2 diabetic patients (p < 0.001). The changes in microvascular reactivity didn't significantly correlate with any of measured parameters of IGF-I/IGFBP system. CONCLUSIONS: Microvascular reactivity is impaired in Type 2 diabetic patients. The function of microcirculation is not significantly related to the particular parameters of the IGF-I/IGFBP system.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Microcirculação/fisiologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The system of IGF-I and its binding proteins is a complex system with many physiological functions including metabolic regulations. Present study was aimed to describe changes of its particular components in patients with type 1 and type 2 diabetic patients and patients with obesity. METHODS AND RESULTS: We examined 21 patients with obesity, 13 patients with type 2 and 22 with type 1 diabetes in comparison with 16 age matched healthy controls. We performed clinical examination and estimation of serum concentrations of IGF-I, free-IGF-I, IGFBP-1, -2, -3 and -6, insulin, C-peptide and fasting glucose. Patients with obesity featured by decreased IGF-I (p < 0.05), free-IGF-I (p < 0.05), IGFBP-1 (p < 0.01) and IGFBP-3 (p < 0.05) serum levels. Type 2 diabetes were associated with a decline of IGF-I (p < 0.05) and IGFBP-2 (p < 0.05) serum levels. Type 1 diabetes was characterised by typical decrease in IGF-I (p < 0.05), free-IGF-I (p < 0.01) and IGFBP-3 (p < 0.01) serum levels as well as by increase in IGFBP-1 (p < 0.01) serum levels. Type 2 diabetic patients had lover IGFBP-2 and higher IGFBP-1 and IGFBP-6 levels than obese subjects. CONCLUSIONS: The study showed a changes in the system of IGF-1 and its binding proteins associated with studied metabolic diseases that confirm active participations of this system in carbohydrate metabolism regulation.
Assuntos
Diabetes Mellitus/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Obesidade/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Ghrelin is a new endogenous ligand for the growth hormone secretagogue receptor. It activates the release of growth hormone from the pituitary and it also participates in the regulation of energy homeostasis. The aim of the study was to characterize changes in serum ghrelin levels in obese subjects and their relationship to the serum levels of leptin and soluble leptin receptor. Eight obese patients (6 women and 2 men) with body mass index (BMI) 40.3+/-13.4 kg.m(-2) and eight healthy controls (5 women and 3 men) with BMI 22.7+/-1.3 kg.m(-2) were examined. The ghrelin serum levels (165.0+/-58.1 vs. 343.37+/-81.96; p<0.001) and soluble leptin receptor serum levels (7.25+/-3.44 vs. 21.80+/-4.99; p<0.0001) were significantly lower in obese patients. The leptin serum levels (23.45+/-12.90 vs. 6.41+/-2.96; p<0.005) were significantly higher compared to the lean subject group. In both measured groups the levels of serum leptin significantly positively correlated with BMI. We proved a significantly lower serum ghrelin levels in the group of obese patients in comparison with the control group.
Assuntos
Leptina/sangue , Obesidade/sangue , Hormônios Peptídicos/sangue , Receptores de Superfície Celular/sangue , Adulto , Índice de Massa Corporal , Feminino , Grelina , Humanos , Masculino , Pessoa de Meia-Idade , Receptores para LeptinaRESUMO
The system of IGF-I and its binding proteins may be involved in the pathogenesis of vascular damage in Type 1 diabetes. The aim of this study was to analyze the relationship between this system and the microvascular reactivity in Type 1 diabetes as measured by laser-Doppler flowmetry. Twenty-two Type 1 diabetic patients (13 women and 9 men) with microangiopathy and fifteen healthy subjects (8 women and 7 men) were examined clinically, underwent laser-Doppler flowmetry and intima-media thickness measurements. Fasting serum levels of IGF-I, free IGF-I, IGFBPs and lipids were examined. The microvascular reactivity was impaired in Type 1 diabetic patients. Maximal perfusion during post-occlusive reactive hyperemia (PORHmax) and during thermal hyperemia (THmax) was significantly decreased in Type 1 diabetes (p<0.01). Percentage perfusion increase in both tests (PORH and TH) was lower in Type 1 diabetes mellitus (p<0.01) and the reaction after heating was slower in diabetic patients (THmax) (p<0.01). We did not find any significant dependence of microvascular reactivity on the parameters of IGF-I or its binding proteins. We conclude that the microvascular reactivity is impaired in Type 1 diabetes mellitus, but this impairment is not clearly dependent on the activity of the IGF-I system. It is probably only a complementary pathogenic factor.
Assuntos
Circulação Sanguínea , Diabetes Mellitus Tipo 1/fisiopatologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Feminino , Humanos , Fluxometria por Laser-Doppler , Masculino , Microcirculação , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
BACKGROUND: An increased cardiovascular risk and mortality in hypopituitary patients receiving conventional hormonal treatment without GH replacement have been shown in several studies. Various atherogenic risk factors including endothelial dysfunction - an early event in the atherogenesis - are more expressed in adults with GH-deficiency (GHD). Changes in microcirculation and vascular reactivity could represent an early marker of developing vascular changes. OBJECTIVE: To evaluate the microcirculation and vascular reactivity in a GHD state before and during GH replacement. SUBJECTS, METHODS AND DESIGN: Thirteen adult patients (ten men, mean age 40+/-9 years) with severe GHD were studied. The skin microvascular perfusion and reactivity were measured by laser-Doppler flowmetry on the forearm. Two dynamic tests for vascular perfusion and reactivity were used - postocclusive reactive hyperemia (PORH) and thermal hyperemia (TH) at 44 degrees C. Measurements were performed before and after 6 and 12 months on GH replacement with a dose of GH that normalized IGF-I serum levels. The parameters of tissue perfusion and vascular reactivity measured in GHD were compared with values during GH treatment and with the results of the control group. RESULTS: Peak flow during TH in GHD patients was significantly reduced before GH treatment when compared with healthy subjects (means+/-s.e.m., 68+/-6.6 vs 111+/-8.3 perfusion units (PU), P<0.001) and normalized on GH treatment (109+/-12.7 PU). The velocity of perfusion increase during TH before treatment was significantly reduced in GHD as well (0.84+/-0.07 vs 1.53+/-0.19 PU/s, P<0.03) and normalized on GH treatment (1.38+/-0.24 PU/s). The PORH was also significantly reduced in GHD compared with controls (PORH(max) 414+/-63 vs 528+/-58%, P<0.05) and during GH treatment was restored to values not different from controls (642+/-86%, P=NS). CONCLUSIONS: Skin microcirculation and vascular reactivity measured by laser-Doppler flowmetry is significantly reduced in GHD adults and is restored during GH replacement therapy. Reduced tissue perfusion and reactivity probably reflect the endothelial dysfunction in the GHD state. Reduced nitric oxide production and bioavailability and also other factors like increased sympathetic activity and reduced conversion of thyroxine to triiodothyronine in the GHD state can contribute to changes in microcirculation. Restoration of vascular reactivity by GH replacement might have favorable clinical consequences on the increased vascular morbidity of GHD patients. Reduced skin microvascular perfusion and reactivity in GHD probably contribute to the impaired thermoregulation - a clinical symptom of GHD.
Assuntos
Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Microcirculação/fisiopatologia , Adulto , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Constrição , Endotélio Vascular/fisiopatologia , Feminino , Antebraço , Temperatura Alta , Humanos , Hiperemia , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Fator de Crescimento Insulin-Like I/análise , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Pele/irrigação sanguíneaRESUMO
The system of insulin-like growth factor-I (IGF-I) and its binding proteins is thought to be involved in the pathogenesis of vascular damage under different pathological circumstances. The results of various studies are rather controversial. This study considers the relationship between the activity of this system and the function of microcirculation in acromegalic patients. Thirteen patients with hormonally active acromegaly and 15 healthy controls were included in the study. The growth hormone, free IGF-I, IGF-I, IGF binding protein (IGFBP) -1, -2, -3 and -6 serum levels and parameters of lipid metabolism were determined. The function of microcirculation was determined by laser Doppler fluxmetry and the intima media thickness of the common carotid artery was measured by ultrasound. We noted significant reduction in postocclusive reactive hyperaemia (PORH(max)) (P < 0.01), in thermal hyperaemia (TH(max)) (P < 0.05) and in the velocity of reaction in both tests in the group of acromegalic patients. A significant negative correlation between free IGF-I serum levels and maximal perfusion during thermal hyperaemia TH(max) (P < 0.02) was found in the control group. Statistically significant positive correlation between free IGF-I serum levels and the time to maximal perfusion in postocclusive reactive hyperaemia PORH(max) (P < 0.05) was found in the group with hormonally active acromegaly. Moreover, a positive relationship between IGFBP-1 serum levels and serum levels of total (P < 0.01) and low density lipoprotein (LDL) (P < 0.05) cholesterol was found in the group of patients with acromegaly. We conclude that the function of microcirculation is impaired in patients with acromegaly and that free IGF-I serum levels may affect the microvascular function as measured by laser Doppler fluxmetry. In addition, we found a significant relationship between the serum levels of IGFBP-1 and those of total and LDL cholesterol in the group of patients with hormonally active acromegaly.
Assuntos
Acromegalia/sangue , Fator de Crescimento Insulin-Like I/biossíntese , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , LDL-Colesterol/sangue , Feminino , Hormônio do Crescimento/sangue , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fluxometria por Laser-Doppler , Metabolismo dos Lipídeos , Masculino , Microcirculação , Pessoa de Meia-Idade , Ligação Proteica , UltrassonografiaRESUMO
Ghrelin is recently discovered peptide hormone involved in the regulation of growth hormone secretion as well as in the regulation of food intake and energetic homeostasis. The study was aimed to describe the changes in ghrelin serum levels in patients with anorexia nervosa and its relationship to some other studied parameters. Sixteen women patients with anorexia nervosa and thirteen healthy women of comparable age were examined clinically and blood samples were taken for estimation of serum levels of ghrelin, leptin, soluble leptin receptor, IGF-I, IGFBP-1 and IGFBP-3. Ghrelin serum levels were significantly increased in the group of patients with anorexia nervosa (p < 0,05). In contrary, serum leptin levels were decreased in the group of patients with anorexia nervosa (p < 0,01). Serum ghrelin levels did not correlate with any other of studied parameters with exception of BMI. We can conclude that serum ghrelin levels are increased in patients with anorexia nervosa and their increase fails to significantly stimulate food intake in this group of patients.
Assuntos
Anorexia Nervosa/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Hormônios Peptídicos/sangue , Adulto , Índice de Massa Corporal , Feminino , Grelina , Humanos , Receptores de Superfície Celular/sangue , Receptores para LeptinaRESUMO
OBJECTIVES: To study the effect of different doses of hGH (biosynthetic human growth hormone--Humatrope) administration on the profile of IGFBP-3 in hypopituitary patients with GHD and to find out the extent of production of IGFBP-3 proteases, which results in the elevated biological IGF-I activity. STUDY DESIGN: Ten patients (after 1. collection) were randomized according to the dose of hGH, administered within three months, into group I: 3 micrograms/kg/day and group II: 6 micrograms/kg/day. After 2. collection the doses of hGH were in both groups duplicated and administered another three months (3. collection). METHODS: RIA's were used to analyse GH, IGF-I, total IGFBP-3 and fIGF-I. The profile of IGFBP-3 forms was studied by electrophoresis with western immunoblotting. RESULTS: Anabolic effect of administered hGH was demonstrated by significant increase of IGF-I and total IGFBP-3 in both groups of patients. It was evident that this increase is associated with the raise of proteolytic fragment of IGFBP-3 (29 kD). CONCLUSION: The increased doses of hGH change the profile of IGFBP-3 in the sense of increasing concentrations of IGFBP-3 (29 kD). As proteolytic clipping of intact IGFBP-3 is associated with the raise of fIGF-I levels in individual patients it is possible to consider 29 kD IGFBP-3 as the marker of the therapy of hGH in our study. However, the increasing tendency to fIGF-I production after 2-fold higher administration of hGH in majority of patients in the trial is not in average significant so it means that the doses of hGH administered to each individual should be optimalized.
Assuntos
Hormônio do Crescimento/deficiência , Hormônio do Crescimento Humano/administração & dosagem , Hipopituitarismo/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Adulto , Western Blotting , Feminino , Hormônio do Crescimento/sangue , Humanos , Hipopituitarismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
The aim of our paper was to calculate referential norms of insulin-like growth factor binding proteins (IGFBPs) in the adult in the Czech Republic, including their dependence on age and sex. The following commercial radioimmunological kits were used for the IGFBPs assessment: IGFBP-1 IRMA (DSL-7800), IGFBP-2 RIA (DSL-7100), IGFBP-3 IRMA (DSL-6600) and IGFBP-6 RIA (DSL-9800). The group consists of 60 serum samples, 31 samples were from men, and 29 samples from women, the average age of the group was 39 +/- 11.7 years. Referential values of IGFBPs in healthy adult population were defined as the average +/- S.D. in mg/l: IGFBP-1 0.038 +/- 0.021; IGFBP-2 0.58 +/- 0.22; IGFBP-3 3.88 +/- 0.73; IGFBP-6 0.22 +/- 0.06. Levels of the mentioned IGFBPs were not affected by gender. In the adult population IGFBP-3 levels were the highest between 20 and 29 years. IGFBP-2 and IGFBP-6 behave contrarity to IGFBP-3. IGFBP-1 does not change with the age. Our results are in agreement with data in literature.
Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Adulto , Idoso , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
In our previous work [7] we demonstrated that the bisphosphonate pamidronate lowered the bone blood flow of non-castrated female rats and inhibited the increase in bone blood flow after oophorectomy (OOX). In this paper we present the results of two similar experiments but also with the estimation of IGF-I in blood. The blood flow in the bones of female rats was estimated by means of 85-Sr microsphere technique (NEN, USA), the blood level of IGF-I was ascertained with Rat IGF-I RIA Kit (DSL, USA). Both experiments A and B were performed on female rats according to the same experimental scheme: group I--sham-operated controls, group II--OOX (four weeks before the experiment), group III--pamidronate (Aredia, CIBA-Giegy, 0.6 mg i.p. three days in the week, for four weeks), group IV--OOX + pamidronate. The results of both experiments can be summarized as follows:--it was confirmed again that OOX rises the circulatory indicators in the bones as well as the blood level of IGF-I;--pamidronate suppresses the increase in bone blood flow after OOX;--pamidronate does not unequivocally influence the level of IGF-I in blood. Thus, it is very probable that IGF-I plays a role in the increase of bone blood flow after OOX. However, it is still not clear how the deficiency of estrogens influences the blood level of IGF-I. The mode of action of pamidronate on the bone blood flow--mainly elevated after OOX--is not clear as well.
Assuntos
Osso e Ossos/irrigação sanguínea , Difosfonatos/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Ovariectomia , Animais , Osso e Ossos/diagnóstico por imagem , Feminino , Pamidronato , Radioimunoensaio , Cintilografia , Ratos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Radioisótopos de EstrôncioRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) represents a frequent endocrinopathy among fertile women. Ethiopathogenesis of the syndrome is multifactorial and it is a subject of scientific discussions. Considered is the possibility of intraovarial IGF system disorder affecting maturation of ovarial folicles. The aim of our work was to determine effects of peroral contraceptives with low-androgen progestin on IGF system in PCOS patients and healthy woman controls. METHODS AND RESULTS: 14 patients fulfilling diagnostic criteria of PCOS and 7 healthy controls were included into the study. All persons were examined before and after six months lasting administration of monophasic estrogen-progesteron contraceptive therapy with 35 micrograms of ethinylestradiol per day and 250 micrograms of low-androgen progestin norgestimate per day. In PCOS patients low increase of basal insulinemia levels occurred (16.3 +/- 4.8 vs. 20.8 +/- 4.8 mU.l-1, p < 0.05). IGF-1 serum levels were not influenced (230 +/- 70 vs. 235 +/- 112 pg.ml-1, n.s.), IGFBP-1 serum concentration significantly increased (46.3 +/- 24.1 vs. 75.6 +/- 24.0 pg.ml-1, p < 0.001). Insulinemia in healthy women also slightly increased (15.9 +/- 4.0 vs. 18.4 +/- 4.0 pg.ml-1, p < 0.05). IGF-1 serum concentration significantly increased (140 +/- 65 vs. 241 +/- 89 pg.ml-1, p < 0.001). IGFBP-1 was also higher (45.0 +/- 19.19 vs. 80.0 +/- 15.6 pg.ml-1, p < 0.001). Influence of the hormonal contraception on the followed parameters was estimated using Wilcoxon's test. While BP-1 increase was significant in both groups, the increase of IGF-1 was significant only in healthy controls. CONCLUSIONS: Increased levels of IGFBP-1 were found in both studied groups of women. Women with PCOS had higher serum levels of IGF-1 before the therapy and the treatment did not influence it. Contrary to it, in healthy women the increased value was observed. Explanation of that finding will become the aim of our next study.
Assuntos
Índice de Massa Corporal , Anticoncepcionais Orais Hormonais/farmacologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Síndrome do Ovário Policístico/sangue , Feminino , Humanos , Insulina/sangue , Hormônio Luteinizante/sangueRESUMO
BACKGROUND: The role of IGF-I/IGFBP's system in the pathogenesis of diabetic vascular complications is widely discussed in the literature. We studied the influence of this system on microvasculature in patients with type 1 diabetes with respect to the effect of IGFBP-1. METHODS AND RESULTS: 17 patients with type 1 diabetes were included in the study. We examined IGF-I, IGFBP-1 and IGFBP-3 serum levels, parameters of compensation of diabetes and basic values of lipid metabolism. The function of microvasculature was examined using the laser-Doppler system Periflux. We didn't found any relation between the total IGF-I serum levels, parameters of lipid metabolism or level of diabetes compensation and the degree of impairment of the function of microcirculation. IGFBP-1 serum levels positively correlated with the peak perfusion in thermal hyperaemia (r = 0.39; p < 0.03). IGFBP-3 serum levels did not affect the function of microcirculation. CONCLUSION: We can conclude that the activity of IGF-I/IGFBP's system belongs to factors contributing to the development of diabetic microangiopathy in type 1 diabetes. IGFBP-1 as the modulator of IGF-I activity plays probably protective role against the progression of microangiopathy. These results correspond with observations of some other authors.
Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fluxometria por Laser-Doppler , Lipídeos/sangue , Masculino , Microcirculação , Pessoa de Meia-Idade , Pele/irrigação sanguíneaRESUMO
The objective was to study the effect of recombinant human growth hormone (rhGH) administration to patients with chronic malnutrition maintained on total parenteral nutrition (TPN) on the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) during a double-blind trial. After 1 week of TPN the patients were randomized into group I (placebo) or group II (rhGH). Samples were collected on the first day (start of the TPN) to measure basal values, the seventh day to study the effect of TPN and the 10th, 14th and 21st days to evaluate the rhGH effect. Basal laboratory evaluation, nutritional status and glucose tolerance were assessed using standard laboratory techniques. Radioimmunoassays were used to analyse IGF-I, free IGF-I (fIGF-I) and IGFBP1-3. Electrophoresis with Western ligand blotting and Western immunoblotting was applied to find the pattern of IGFBPs. TPN had no effect on the circulating IGF-I concentration and the pattern of IGFBPs present in the studied groups of patients. The rhGH administration led to significant increases of IGF-I, total IGFBP-3, glycosylated IGFBP-3 (39, 42 kDa) and the 29 kDa fragment of IGFBP-3 and the decrease of IGFBP-2 during the trial (P<0.05). The mean levels of IGFBP-1, fIGF-I and the parameters of nutritional status in group II during the trial were not significantly influenced by rhGH. However, it has been found that IGFBP-1 and fIGF-I levels were correlated with the levels of the weekly nitrogen balance of each patient in group II at the end of the trial. In spite of the significant changes of IGF-I, IGFBP-2, total IGFBP-3 and IGFBP-3 (29 kDa proteolytic fragment) after rhGH administration to patients with malnutrition, maintained on parenteral nutrition, the increase of nitrogen balance was seen only in patients who decreased their IGFBP-1 and increased bioavailable IGF-I as reflected by measurement of fIGF-I. The levels of IGFBP-1 may provide a useful marker of IGF-I bioavailability in monitoring the efficiency of the rhGH therapy in malnourished patients.
Assuntos
Hormônio do Crescimento Humano/farmacologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Nutrição Parenteral Total , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Pessoa de Meia-Idade , Nitrogênio/metabolismo , Distúrbios Nutricionais/sangue , Distúrbios Nutricionais/metabolismo , Distúrbios Nutricionais/terapia , Fragmentos de Peptídeos/sangue , Fatores de TempoRESUMO
The IGF-I system and its binding proteins participate in the pathogenesis of vascular affections under various pathological conditions. The mechanism and mode of its action were however not elucidated in details so far and views on its role are controversial. The objective of the study was to assess the relationship of this system and the blood flow in the microcirculation in obese patients. The authors examined 21 obese patients (BMI 39.7 +/- 7.3 kg/m2) and a group of healthy volunteers. They examined: serum concentrations of total IGF-I, free IGF-I, IGFBP-1,-2,-3, and -6, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides as well as the intimomedial thickness of the common carotid arteries and parameters of blood flow in the microcirculation, evaluated by a laser-Doppler examination. In obese patients there were significantly lower serum concentrations of IGF-I and free-IGF I (p < 0.05) as compared with the control group. Comparison of the function of the microcirculation revealed in obese patients, as compared with the control group, a lower percentage increase of perfusion after occlusion (PORH%, p < 0.05) and after heating (TH%, p < 0.05) and a slower onset of thermal hyperaemia (THmax/t, p < 0.05). In the control group serum concentrations of free-IGF-I correlated inversely with the maximum perfusion after heat induced hyperaemia (THmax (r = -0.54, p < 0.02) and the rate of onset of hyperaemia after heating (THmax/t) (r = 0.51, p < 0.02). In the group of obese patients serum concentrations of free-IGF-I correlated inversely with the maximum perfusion after heat induced hyperaemia (THmax) (r = -0.55, p < 0.02), and IGFBP-3 concentrations correlated inversely with maximum hyperaemia after occlusion (PORGmax) (r = -0.57, p < 0.01). The results suggest that the function of the microcirculation in obese subjects is affected. The activity of the IGF-I system and its binding proteins is related to the affected function of the microcirculation and a negative part is played particularly by serum concentrations of free IGF-I. The negative effect of IGFBP-3 on the function of the microcirculation is surprising.
Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Microcirculação , Obesidade/fisiopatologia , Pele/irrigação sanguínea , Velocidade do Fluxo Sanguíneo , Colesterol/sangue , Feminino , Antebraço , Humanos , Hiperemia/fisiopatologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Fluxometria por Laser-Doppler , Masculino , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Obesidade/sangue , Triglicerídeos/sangueRESUMO
So far it is not known whether the growth hormone (GH) has an effect on the local blood circulation in bones. Using male rats we studied the local blood circulation in the tibia and the distal end of the femur (by means of the uptake of 85Sr-microspheres), the density and ash weight of the tibia, the urinary excretion of pyridinoline (PD) and deoxypyridinoline (DPD) as an indicator of bone resorption and the blood levels of IGF-I after the administration of human GH (4 mg/kg s.c. daily for 4 weeks) and/or bisphosphonate pamidronate (Aredia, CIBA-Geigy, administered in the dose of 3 mg/kg i.p. on day 1, 2, 9 and 10). The rats were divided into four groups: 1. controls, 2. GH, 3. pamidronate, 4. GH plus pamidronate. After the administration of GH, we observed a significant increase in bone blood flow (and in the uptake of 85Sr-microspheres), a decrease in the density and ash weight of the tibia and increased urinary excretion of PD and DPD; IGF-I levels in the blood were non-significantly elevated. Simultaneously administered pamidronate inhibited all significant effects of GH and it also decreased the IGF-I levels in rats treated with GH. After the administration of pamidronate itself the bone density and ash weight of the tibia were increased and urinary DPD excretion was decreased. In view of the known vascular effects of IGF-I, we assume that the increase in bone blood flow after the administration of GH and its reduction after simultaneous administration of pamidronate could be mediated by the changes of IGF-I blood levels, although the effect of pamidronate on IGF-I is still not clear. Regarding the role of blood circulation in rat bones, we consider that our present results are further evidence for the relationship between the blood circulation in bones and bone resorption, although these results do not show how active is bone blood circulation in the regulation of bone tissue metabolism.