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Journal Article 2011; 32(6): 857-864 PubMed PMID: 22286784 Citation  Keywords:  Adult, Body Mass Index, Estradiol:blood, Female, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor Binding Protein 3:blood, Insulin-Like Growth Factor I:metabolism, Young Adult,.   

OBJECTIVE: To compare the influence of low and normal endogenous estradiol concentration on circulating hGH, IGF-I and IGFBP-3 levels as well as on mutual correlations of these parameters.

PATIENTS: 45 women (age 30.7 ± 9.0 years, BMI 25.7 ± 8.0) divided into group A - 15 hypoestrogenic women and group B - 30 normoestrogenic controls. Neither of the women was menopausal nor hyperprolactinemic.

METHODS: Blood sample was taken at the standard conditions prior to the initiation of hormonal supplementation therapy in group A and at the day 3-5 of menstrual cycle in group B. Serum hGH, IGF-I, IGFBP-3, insulin, testosterone, sex hormone binding globulin (SHBG) dihydroepiandrosterone sulphate (DHEAS) and LH as well as prolactin (PRL), FSH and estradiol levels were measured by standard RIA kits.

RESULTS: Mean IGF-1, LH, FSH, testosterone and estradiol and PRL plasma levels were lower in group A compared to group B. There were no significant differences in mean SHBG, insulin and DHEAS levels. There were also no differences in mean: age, body mass, BMI as well as percentage of each BMI range between groups. Regardless the estradiol level the IGF-I/age link was found in both groups. A IGF-I/IGFBP-3 relation was found in both groups. IGF-I/estradiol link was seen only in group A. In group B hGH/SHBG link was found, in group A this relation was indirect. A link between hGH and testosterone levels was found only in group B. SHBG was related in group B to IGFBP-3, testosterone and to DHEAS. Insulin/IGFBP-3 link was seen in group B. The stepwise multiple regression revealed DHEAS and LH as predictors of IGF-I level in group A, while in group B none of the parameters predicted IGF-I level. The results of the same analysis in case of hGH are as follows: in group A hGH level was predicted by estradiol and SHBG. In group B none of factors predicted hGH levels.

CONCLUSION: Estradiol plasma level is correlated to circulating IGF-I, albeit the relation seems to be biphasic....

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Journal Article 2011; 32(2): 148-153 PubMed PMID: 21552189 Citation  Keywords:  Aged, Biomarkers:blood, Chronic Disease, Circadian Rhythm:physiology, Erythropoietin:blood, Female, Glomerular Filtration Rate:physiology, Hemoglobins:metabolism, Humans, Insulin-Like Growth Factor I:metabolism, Interleukin-6:blood, Kidney:physiopathology.   

OBJECTIVE: Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function.

METHODS: The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations.

RESULTS: Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found.

CONCLUSION: The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia....

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Journal Article 2010; 31(4): 517-523 PubMed PMID: 20802456 Citation  Keywords:  Analysis of Variance, Animals, Ferrous Compounds:pharmacology, Growth Hormone:pharmacology, Insulin-Like Growth Factor I:pharmacology, Lipid Peroxidation:drug effects, Liver:drug effects, Malondialdehyde:metabolism, Rats, Swine, Thyroid Gland:drug effects.   

OBJECTIVES: Growth hormone (GH) and its tissue mediator, insulin-like growth factor-I (IGF-I), are involved in oxidative processes, lipid peroxidation (LPO) included. Bivalent iron (Fe2+) is frequently used to experimentally induce oxidative damage to macromolecules (Fe2++H2O2+H+→Fe3++•OH+H2O). The aim of the study was to evaluate the effect of GH and/or IGF-I on the iron-induced LPO in the rat liver and porcine thyroid homogenates.

METHODS: Rat liver and porcine thyroid homogenates were incubated in presence of GH (100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or IGF-I (1000; 100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001 µg/ml) or GH (100 µg/ml)+IGF-I, or FeSO4+H2O2 plus GH and/or IGF-I. The level of LPO was expressed as concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) per mg of protein.

RESULTS: GH and/or IGF-I did not change the basal level of oxidative damage to lipids. In the rat liver homogenates, GH did not affect the iron-induced LPO, whereas IGF-I--in the lowest two concentrations--enhanced the process. In porcine thyroid homogenates, GH--in its two lowest concentrations--prevented, whereas in other concentrations, it enhanced the iron-induced LPO. IGF-I, in all used concentrations, enhanced the iron-induced LPO.

CONCLUSION: GH and/or IGF-I may reveal prooxidative effects. This fact does not support their application in the treatment of disorders associated with increased oxidative damage....

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Journal Article 2010; 31(2): 256-260 PubMed PMID: 20424577 Citation  Keywords:  Acromegaly:blood, Adult, Cathepsin B:blood, Cysteine Proteinase Inhibitors:blood, Female, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:metabolism, Male, Middle Aged,.   

OBJECTIVE: Acromegaly is a rare disease due to growth hormone (GH) excess. Patients must be carefully follow up because of mortality and co-morbidity increased risks. Since routinely used GH and insulin-like growth factor-1(IGF-1) estimations are not always sufficient, patients require assessment of organ- or tissue-specific tests. Cysteine proteases (CP), including cathepsin B, have been tested in a number of pathologies in respect of a role in pathogenesis and potential utility in the disease activity and prognosis assessment. There is lack of data on CP activity in acromegaly.

MATERIALS AND METHODS: In present study cathepsin B-like and cysteine peptidase inhibitor (CPI) activities have been tested in 29 acromegaly patients and in 15 healthy controls. Cathepsin B activity was assayed with N-bansoyl-DL-arginine-beta-naphthylamide (BANA) as substrate by the Barrett method. CPI activity was determined by measuring the inhibition of papain.

RESULTS: Serum cathepsin B activity (median: 1.38 U/ml) and CPI activity (median: 93.08 U/ml) were higher in acromegaly then in controls (0.93 U/ml and 82.55 U/ml, p=0.000017 and 0.00285, respectively). Neither cathepsin B nor CPI activity was correlated with GH or IGF-1 level. No correlation was recorded between cathepsin B and CPI activity.

CONCLUSION: It was shown for the first time that cathepsin B and CPI activities are increased in acromegaly. These findings suggest to study cathepsin system as an adjuvant parameter in the assessment of the overall acromegaly complications. Moreover, CP may be involved in pathomechanism of organ complications in acromegaly and may interfere with IGF-1 action....

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Journal Article 2009; 30(4): 501-505 PubMed PMID: 20010501 Citation  Keywords:  Adenosine, Birth Weight:genetics, Body Height:genetics, Child Development:physiology, Cytosine, Female, Humans, Infant, Infant, Newborn, Infant, Small for Gestational Age:growth & development, Insulin-Like Growth Factor I:genetics, Male, Polymorphism, Gen.   

BACKGROUND: IGF-I gene polymorphisms might alter IGF-I level resulting in decreased foetal and postnatal growth and increased risk for diabetes mellitus type 2 and cardiovascular diseases in adulthood.

OBJECTIVES: We analyzed the association between Cytosine-Adenosine (CA)10-24 repeats polymorphism in promoter region of the IGF-I gene and early growth in infants with birth weight appropriate for gestational age (AGA) and small for gestational age (SGA).

DESIGN AND METHODS: All neonates were born at term, 196 of them were AGA and 26 SGA. Blood for DNA analyses was obtained from placental part of umbilical vein. Genotyping was performed using fragment analyses of IGF-I gene promoter region. The data about postnatal growth in the group of AGA children were obtained at the age of 18 months, in SGA children at 12 months.

RESULTS: No differences in the frequency of wild type allele with (CA)19 repeats and polymorphisms with (CA)<19 or (CA)>19 repeats were observed between AGA and SGA children. The average birth weight and length in AGA wild type (CA)19 homozygotes were lower in comparison with AGA carriers of various (CA)n polymorphisms but all observed anthropometric differences disappeared at the age of 18 months. In SGA children, no differences were found between number of (CA)n repeats and anthropometric parameters both at birth and at the age of 12 months.

CONCLUSIONS: Although (CA)n repeats polymorphism in IGF-I gene might affect prenatal growth in AGA children, our results have not shown any impact of variable number of (CA) n repeats in IGF-I gene on postnatal growth....

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Journal Article 2009; 30(3): 382-386 PubMed PMID: 19855364 Citation  Keywords:  Acromegaly:blood, Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Chi-Square Distribution, Diagnosis, Differential, Female, Goiter, Nodular:blood, Human Growth Hormone:blood, Humans, Incidence, Insulin-Like Growth Factor I:metabolism, Male, Middle Ag.   

OBJECTIVE: The high prevalence of goiter in acromegalic patients is well known. Several studies revealed increased frequency of thyroid carcinoma in these patients. The aim of the study was to evaluate the incidence of thyroid lesions, including thyroid cancer in acromegalic patients and to estimate possible factors influencing their occurrence, especially high IGF-1 level.

MATERIALS AND METHODS: 86 consecutive patients with acromegaly were retrospectively analyzed. 45 patients had been previously treated for acromegaly and 41 were newly diagnosed. In all subjects hGH, IGF-1, TSH, FT4 levels were determined. Thyroid gland was evaluated in ultrasound examination. Fine needle aspiration biopsy (FNAB) was performed in every solid or mixed thyroid nodule.

RESULTS: Thyroid morphology abnormalities were found in 75 patients (87.2%). 10 patients (11.6%) had diffuse goiter and 65 patients (75.6%) had nodular goiter. There were 5 cases of thyroid carcinoma (5.8%): 3 papillary carcinomas and two follicular variants of papillary cancer. Out of five cancers three were multifocal, one infiltrated thyroid capsule and one was diagnosed at the stage of metastases to four lymph nodes.

CONCLUSIONS: Our study confirmed common co-existence of acromegaly and thyroid lesions. Furthermore, it revealed considerably high occurrence of thyroid carcinoma in these patients. In view of this correlation, the potential role of IGF-1 in pathogenesis of benign and malignant thyroid neoplasms should be considered. Due to high frequency of thyroid cancer in acromegalic patients, we suggest to perform fine needle aspiration biopsy in each case of thyroid nodule....

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Journal Article 2008; 29(6): 981-989 PubMed PMID: 19112400 Citation  Keywords:  Amino Acid Substitution:genetics, Animals, Cattle:genetics, Female, Gene Expression Regulation:genetics, Haplotypes, Insulin-Like Growth Factor I:genetics, Liver:metabolism, Male, Polymorphism, Single Nucleotide:genetics, Receptors, Somatotropin:genetics,.   

BACKGROUND: Polymorphisms in the bovine ghr and igf1 genes. Ghr and igf1 genes have been associated with milk and meat production of cattle. However, the molecular and physiological mechanisms underlying such associations are unknown. The objective of this study was to examine the effects of polymorphisms in 5'-regions of the bovine ghr and igf1 genes on the igf1 gene expression in the liver and on the level of IGF1 in blood of Polish Holstein-Friesian cattle.

METHODS: Individual and combined effects of single nucleotide polymorphisms (SNPs) in the 5'noncoding regions of the bovine igf1 and ghr genes on the IGF1 level in blood and igf1 gene expression in liver were examined. One SNP in the igf1 gene and four SNPs in the ghr gene were analyzed. IGF1 level in blood was measured by radioimmunoassay (RIA) in 211 heifers and bulls of Polish Holstein-Friesian cattle (of Black-and-White type). The igf1 gene expression was measured in livers of bulls carrying different igf1 and ghr genotypes (from three to nine animals per genotype) using real-time reverse transcription-PCR methods with the gapdh gene as a reference.

RESULTS: We showed that C/T transition in the promoter region of the igf1 gene influences the gene expression; relative igf1 expression was higher for animals with the CC genotype than for those with the TT and CT genotypes. TESS analysis showed that C/T transition in the igf1 gene co-localizes with the NF1 transcription factor binding site. Also, the ghr genotype appeared to significantly influence the igf1 gene expression in the liver, and we found the highest expression for the genotypes: RFLP-AluI (AT), RFLP-Fnu4HI(CC), and RFLP-NsiI(GA), and for the combined ghr genotype: AluI(AT)/ Fnu4HI(CC)/NsiI(GA). We discovered a significant association between the igf1 genotype and the IGF1 blood level. The highest IGF1 content in blood serum was found in CC genotype animals (1024 ng/ml) vs 698 ng/m and 859 ng/min in the TT and CT igf1 genotypes, respectively. Moreover, we noticed significant differences between ghr genotypes. The highest blood levels of IGF1 were for the animals carrying the ghr genotypes: RFLP-AluI(AA), RFLP-Fnu4HI(CC), and RFLP-NsiI(AG). Ghr haplotypes also significantly affected the IGF1 blood level. Animals of the combined ghr genotypes AluI(AA)/AccI(CC)/Fnu4HI(CC)/NsiI(AG) and AluI(AA)/AccI(CT)/Fnu4HI (CC)/ NsiI(AG) had a higher IGF1 concentration in blood than other genotype carriers.

CONCLUSIONS: The present results indicate that the effects of polymorphism in the igf1 and ghr genes on cattle milk or meat production traits could be at least partially mediated through their effects on the igf1 gene expression in the liver and the IGF1 level in blood....

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Journal Article 2008; 29(6): 1038-144 PubMed PMID: 19112390 Citation  Keywords:  Acromegaly:blood, Adenoma:complications, Adult, Aged, Follow-Up Studies, Humans, Insulin-Like Growth Factor I:analysis, Male, Middle Aged, Pituitary Neoplasms:complications, Somatostatin:analogs & derivatives, Treatment Outcome,.   

OBJECTIVE: The aim of our study was to investigate the characteristics of acromegalic patients diagnosed at a tertiary University Hospital and to evaluate the results of the recommended treatment protocols.

PATIENTS AND METHODS: All our acromegalic patients were included (n=48; 27 women). Demographic, hormonal, visual and imaging data at diagnosis and during follow-up were recorded, as well as the treatments applied.

RESULTS: In 73.0% of the patients, acromegaly was due to a pituitary macroadenoma. From those under periodic surveillance, 68.2% underwent surgery and 36.4% had radiotherapy. At the time of the study 88.6% of the patients were receiving medical therapy, 28.2% of them as first-line treatment. Applying current criteria, only one patient was cured by surgery. Considering normal age and sex-matched concentrations of IGF-I as a control criteria, surgery resulted in disease control in 10% of the patients who had surgery, while medical treatment controlled the disease in 76.9% (P <0.05). Of those who receive medical therapy as first-line treatment, tumour size decreased in 45.5%, while in the rest no significant changes were observed during follow-up.

CONCLUSIONS: Not all centres obtain the results reported in the literature in terms of disease control and morbidity after surgical treatment of growth hormone-secreting tumours. It is possible that in some hospitals first-line medical treatment should be chosen, unless the patient has visual disturbances, as long as it is not clear that partial surgical removal of the tumour significantly improves response to medical therapy or reduces its costs....

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