Serum Growth Hormone Levels Research Articles

Surgical management of acromegaly: Long term functional outcome analysis and assessment of recurrent/residual disease.

Context:Functional growth hormone producing adenomas have long-term deleterious effects on the visual apparatus, the cardiovascular and musculoskeletal systems, and often predispose to malignancies. Since persistence of acromegaly affects outcome and quality of life, therapeutic interventions become mandatory.Aim:This study represents an analysis of long-term clinical and endocrinal outcome of 115 patients of acromegaly after surgical management.Setting and Design:Tertiary care retrospective study.Materials and Methods:One hundred and fifteen patients (male:female ratio: 1:1.09) with acromegalic features were studied. Apart from acromegalic features, their main clinical presentation also included headache, diminution of vision, field defects, ptosis, irregular menstruation, diabetes insipidus, diabetes mellitus and hypertension. Six of them presented with apoplexy. Their preoperative endocrinal evaluation included basal and suppressed growth hormone (GH), prolactin and thyroid levels. On the basis of axial and coronal CT scan or multiplanar MR imaging or both, the tumors were classified according to their suprasellar and parasellar extension (Hardy's grade). Transnasal trans-sphenoidal surgery (TSS) (n = 37) and sublabial, rhinoseptal TSS (n = 72) were the preferred approaches. Six patients with significant parasellar extensions underwent trans-cranial explorations. The patients were followed up at 6 and 12 weeks and then at 6 monthly intervals. Hormonal and CT/MR evaluation were also done. Attainment of random GH value less than 2.5 µg/L, and the nadir GH value after oral glucose tolerance test (OGTT) less than 1 µg/L were used as the criteria of cure.Findings:The patients were preoperatively in Hardy's tumor grade 0 (29), A (21), A+E (3), B (21), B+E (5), C (9), C+E (10), D (1) D+E (11), E (5), respectively. One hundred and one patients were available for follow-up (FU; median FU duration: 84 months; range: 6 to 132 months). Surgical cure was achieved in 73 patients following the first surgery; and, in 10 additional patients following a second intervention. No patient with a preoperative grade 0, A, B, C had a recurrence after attaining the initial remission. Recurrence after an initial cure occurred in 7 patients (overall remission rate following surgery: 75.24%). The preoperative grade of the latter patients was A+E:1, B+E:1, C+E:1, D:1, D+E:2, E:1, respectively. All these patients underwent subsequent radiotherapy (RT). The twelve patients with persistent symptoms and high GH levels following surgery underwent RT; six others with improved symptoms despite high GH levels were kept under strict observation. There was no surgical mortality.Conclusions:A high remission rate without significant morbidity could be achieved following surgical intervention in acromegalic patients. Following surgery, tumors with greater than or equal to 3 cm suprasellar height and without parasellar extension had no clinical recurrence at FU. A continuous monitoring is mandatory to pick up relapsed cases as well as those who develop delayed signs of hypopituitarism. A subset of patients who show clinical improvement following surgery but still have higher GH levels may be followed up without additional therapy unless clinical signs reappear or the serum GH levels progressively increase.

Is really endogenous ghrelin a hunger signal in chickens? Association of GHSR SNPs with increase appetite, growth traits, expression and serum level of GHRL, and GH

Chicken growth hormone secretagogue receptor (GHSR) is a receptor for ghrelin (GHRL), a peptide hormone produced by chicken proventriculus, which stimulates growth hormone (GH) release and food intake. The purpose of this study was to search for single nucleotide polymorphisms (SNPs) in exon 2 of GHSR gene and to analyze their effect on the appetite, growth traits and expression levels of GHSR, GHRL, and GH genes as well as serum levels of GH and GHRL in Mandara chicken. Two adjacent SNPs, A239G and G244A, were detected in exon 2 of GHSR gene. G244A SNP was non-synonymous mutation and led to replacement of lysine amino acid (aa) by arginine aa, while A239G SNP was synonymous mutation. The combined genotypes of A239G and G244A SNPs produced three haplotypes; GG/GG, GG/AG, AG/AG, which associated significantly (P<0.05) with growth traits (body weight, average daily gain, shank length, keel length, chest circumference) at age from >4 to 16w. Chickens with the homozygous GG/GG haplotype showed higher growth performance than other chickens. The two SNPs were also correlated with mRNA levels of GHSR and GH (in pituitary gland), and GHRL (in proventriculus and hypothalamus) as well as with serum level of GH and GHRL. Also, chickens with GG/GG haplotype showed higher mRNA and serum levels. This is the first study to demonstrate that SNPs in GHSR can increase appetite, growth traits, expression and level of GHRL, suggesting a hunger signal role for endogenous GHRL.

The influence of type 2 diabetes on serum GH and IGF-I levels in hospitalized Japanese patients

ObjectiveAlthough serum insulin like growth factor type 1 (IGF-I) levels are negatively correlated with hemoglobin A1c (HbA1c) in patients with type 1 diabetes, this correlation is controversial in patients with type 2 diabetes mellitus (T2DM) because of the influence of multiple factors including insulin secretion and obesity. The aim of this study was to evaluate the influence of T2DM on serum growth hormone (GH) and IGF-I levels in Japanese patients, who exhibited relatively low BMI compared with white patients in the previous studies. DesignWe retrospectively analysed 315 consecutive Japanese hospitalized patients with T2DM. We analysed factors correlated with changes in serum IGF-I levels and those related to diabetes. ResultsThe median HbA1c was 8.7% (7.4–10.2) and the median body mass index (BMI) was 26.2kg/m2 (23.1–29.7), which was relatively low compared with the previous studies. Overall, no correlations was found between serum GH or IGF-I levels and fasting plasma glucose (FPG) or HbA1c; however, when stratified by FPG and HbA1c levels, serum IGF-I levels were significantly lower in patients with FPG≥200mg/dL than in those with FPG<200mg/dL (p=0.039). In addition, serum IGF-I levels were significantly lower in patients with HbA1c≥12% than in those with HbA1c<12% (p=0.046). Multiple linear regression analysis revealed a positive correlation between fasting C-peptide levels and serum IGF-I levels (p=0.040), whereas no correlations was found for BMI, duration of T2DM, FPG levels, or HbA1c. Moreover, patients with improved HbA1c levels during the follow up period showed a significant increase in serum IGF-I levels. ConclusionsSerum IGF-I levels were significantly decreased in Japanese patients with uncontrolled T2DM, and impaired insulin secretion may be a mechanism underlying this effect. When diagnosing acromegaly in patients with uncontrolled diabetes, these factors should be taken into account.

Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3.

Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly

Background: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly.Methods: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined.Results: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively).Conclusions: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.

Effects of Aqueous Extract of Phyllostachyos Caulis in Taeniam on Longitudinal Bone Growth in Adolescent Rats.

This study examined whether treatment with Phyllostachyos Caulis in Taeniam aqueous extract improves longitudinal bone growth in adolescent male rats. Three-week-old male Sprague-Dawley rats were divided into three groups: a control group, a Phyllostachyos Caulis in Taeniam group (200 mg/kg, p.o.), and a recombinant human growth hormone group (20 µg/kg, s.c.). The total tibial length and the height of each growth plate zone were evaluated by radiography and histomorphometry. The total number of proliferative cells and 5-bromo-2'-deoxyuridine-positive cells were counted after 5-bromo-2'-deoxyuridine staining. Serum total osteocalcin levels were assayed using an enzyme-linked immunosorbent assay. The average total tibial length of the Phyllostachyos Caulis in Taeniam group was significantly longer than that of the control group. The heights of the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group were increased, and the ratio of 5-bromo-2'-deoxyuridine-positive to total cells in the proliferative zone was also increased. The serum osteocalcin, growth hormone, and insulin-like growth factor-1 levels were significantly increased in the Phyllostachyos Caulis in Taeniam group compared to the control group. Insulin-like growth factor-1 and insulin-like growth factor-1 receptor were highly expressed in the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group. The Phyllostachyos Caulis in Taeniam extract increased bone length, promoted cell proliferation, and activated the growth plate zones, which suggested that the extract could play an important role in longitudinal bone growth. Therefore, the Phyllostachyos Caulis in Taeniam extract might be a good alternative medicine to growth hormone therapy.

Nanosize of zinc oxide and the effects on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets

The aim of this study was to investigate the effect of dietary supplementation of nanosize zinc on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Ninety-six LYD weanling piglets were assigned to control, zinc oxide (ZnO), organic-Zn (Zn-methionine) and nanosize ZnO (nano-Zn) groups with four replicates. The zinc was at the 120 mg/kg level in the treatment group's diet, while the control group's was 80 mg/kg Zn. The experiment results indicated that the nano-Zn and organic-Zn groups had significantly higher Zn digestibility compared to the ZnO and control groups. For the immune response traits, the IgG level and goat red blood cells (GRBC) antibody titer were nano-Zn and organic-Zn>ZnO>control; in the phytohemagglutinin (PHA) challenge test result, nano-Zn>organic-Zn>ZnO>control; in regard to the γ-globulin level, nano-Zn and organic-Zn>ZnO and control, with significant difference between groups. In the serum parameters aspect, serum Zn concentration in nano-Zn and organic-Zn groups were higher than in the ZnO and control groups, serum growth hormone concentration was increased in the nano-Zn group than in the other groups. In conclusion, nanosize zinc oxide for dietary supplementation can increase zinc digestibility, serum growth hormone levels and carbonic anhydrase activity and enhance the immune response of weanling piglets.

Effects of nanosize zinc oxide on zinc retention, eggshell quality, immune response and serum parameters of aged laying hens

The aim of this study was to investigate how dietary supplementation of nanosize zinc oxide affect zinc retention, egg production and eggshell quality, immune response and serum parameters of aged layers. In trial 1, twenty white Leghorn laying hens (68weeks-old) were assigned to the control, ZnO, organic-Zn (Zn-methionine) and nano-Zn (nanosize ZnO) groups. The Zinc was maintained at a 60mg/kg level in the treatment groups’ diet, while the control group’s diet contained 40mg/kg Zn to evaluate the nutrient retention and zinc bioavailability. In trial 2, eighty old white Leghorn laying hens (68weeks-old) were randomly allotted to four dietary treatments (as trial 1) to evaluate the egg production and eggshell quality, immune response and serum parameters. The results of trial 1 indicated that there were no differences in nutrient retention among the groups, but zinc retention was significantly higher in the nano-Zn and organic-Zn groups than that in the control and ZnO groups (P<0.05). Trial 2 results indicated that eggshell thickness was increased in the nano-Zn and organic-Zn groups compared to the control group (P<0.05); immune responses parameters, including: PHA (phytohemagglutinin) skin challenge test result, GRBC (goat red blood cells) antibody titer and IgG levels exhibited no differences among the groups; serum growth hormone concentration and carbonic anhydrase activity was significantly higher in the nano-Zn and organic-Zn groups compare to control group (P<0.05); serum albumin concentration in organic-Zn group was lower than that of the control group (P<0.05). In conclusion, nanosize zinc for dietary supplementation can increase zinc retention, as well as enhance eggshell thickness, serum carbonic anhydrase activity and growth hormone level of layers. We therefore concluded that nanosized zinc oxide can enhance zinc absorption in the intestine of layers compare to regular zinc oxide.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

Effect of the co-administration of glucose with morphine on glucoregulatory hormones and causing of diabetes mellitus in rats.

Background:Morphine is related to dysregulation of serum hormone levels. In addition, addict subjects interest to sugar intake. Therefore, this study investigated the effect of co-administration of glucose with Mo on the glucoregulatory hormones and causing of diabetes mellitus in rats.Materials and Methods:Male rats were randomly divided into four groups including, control, morphine, Morphine-Glucose and diabetes groups. Morphine was undergone through doses of 10, 20, 30, 40, 50, and 60 mg/kg, respectively on days 1, 2, 3, 4, 5, and 6. Then, dose of 60 mg/kg was used repeated for 20 extra days. The Morphine-Glucose group received the same doses of morphine plus 1 g/kg glucose per day. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. At the end of experiment, the serum insulin, glucagon, growth hormone (GH), cortisol, and glucose levels were measured. The homeostasis model assessment (HOMA) indexes concluding the HOMA-insulin resistance (HOMA-IR) and HOMA-β were evaluated.Results:Morphine insignificantly induced a hyperglycemia condition and insulin resistance. Whereas, the beta-cell functions significantly (P < 0.05) decreased only in morphine group. The co-administration of glucose slightly increased the GH, and increased insulin and cortisol levels significantly (P < 0.05 and P < 0.01; respectively) in the Morphine-Glucose group. Furthermore, the co-administration of glucose with morphine could nearly modulate the morphine effects on body weight, glucose, and glucagon levels.Conclusion:It is probable that the co-administration of glucose with morphine modulate the serum glucose levels by stimulating the beta-cell functions and to increase insulin secretion.

Continuing efforts to standardize measured serum growth hormone values in Japan.

Determination of serum growth hormone (GH) levels is mandatory for diagnosis of GH deficiency and excess. In the present study, we, the Study Committee for GH and Its Related Factors, The Foundation for Growth Science, Japan measured GH values in serum samples using all the commercially available kits in Japan. Significant discrepancies in the GH values were observed among the kits in spite of using the unified recombinant human GH-based standards. To deal with the discrepancies, we established a formula using a linear structural relationship model and were able to standardize the GH values. We propose to use the formula to diagnose GH deficiency and excess in Japan.

Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300mg/kg copper sulfate for 80days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

Transgenic Wuzhishan minipigs designed to express a dominant-negative porcine growth hormone receptor display small stature and a perturbed insulin/IGF-1 pathway.

Growth hormone (GH) is an anabolic mitogen with widespread influence on cellular growth and differentiation as well as on glucose and lipid metabolism. GH binding to the growth hormone receptor (GHR) on hepatocytes prompts expression of insulin growth factor I (IGF-1) involved in nutritionally induced compensatory hyperplasia of pancreatic β-cell islets and insulin release. A prolonged hyperactivity of the IGF-1/insulin axis in the face of insulinotropic nutrition, on the other hand, can lead to collapse of the pancreatic islets and glucose intolerance. Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism. However, these individuals enjoy a reduced prevalence of acne, cancer and possibly diabetes. Minipigs have become important biomedical models for human conditions due to similarities in organ anatomy, physiology, and metabolism relative to humans. The purpose of this study was to generate transgenic Wuzhishan minipigs by handmade cloning with impaired systemic GHR activity and assess their growth profile and glucose metabolism. Transgenic minipigs featuring overexpression of a dominant-negative porcine GHR (GHR(dm)) presented postnatal growth retardation and proportionate dwarfism. Molecular changes included elevated GH serum levels and mild hyperglycemia. We believe that this model may prove valuable in the study of GH functions in relation to cancer, diabetes and longevity.

DMP-1-mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH.

Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF-1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF-1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)-1-mediated Ghr knockout (DMP-GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP-GHRKO did not affect linear growth but compromised overall bone accrual. DMP-GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte-like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase-2 and IGF-1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth.

Immune stimulation improves endocrine and neural fetal outcomes in a model of maternofetal thyrotoxicosis

The potentiation of the immune system in pregnant rats was performed with Complete Freund's Adjuvant [CFA; 20μl, subcutaneous at gestation day (GD) 18] in experimentally-induced hyperthyroidism by Levo-thyroxine (L-T4; 10μg/100g of b.w., intraperitoneal from GD 2 to 17). The potential effects on the fetal neuroendocrine function were evaluated by observing some histopathological investigations in pregnant rats and measuring some biochemical parameters in dams and their fetuses at GD 20. In hyperthyroid group, an increase in maternofetal serum thyroxine (T4), triiodothyronine (T3) and a decrease in thyrotropin (TSH) levels were noticed, while the concentrations of fetal serum growth hormone (GH) and insulin-like growth factor-1 (IGF1) levels were increased at tested GD with respect to control and CFA groups. Moreover, the activity of uterine and placental myeloperoxidase (MPO) was increased (P<0.001) in CFA and CFA-treated hyperthyroid groups in respect to control or hyperthyroid groups, respectively. The gestational thyrotoxicosis led to some histopathological lesions in uterine and placental tissues characterized by severe degeneration in trophoblast spongioblast cell layer with congestion, mild congested blood vessels in the endometrium and deficient in spiral artery remodeling. Although, the elevation in fetal serum transforming growth factor-beta (TGFβ) and cerebellar monoamines [norepineprine (NE), epinephrine (E), dopamine (DA) and 5-hydroxytryptamine (5-HT)] was observed, the reduction in fetal serum tumor necrosis factor-alpha (TNFα) and adipokines (Leptin and adiponectin) was detected. Treatment of dams with CFA showed an obviously reversing and protecting effect against hyperthyroid perturbations. Thus, the maternal CFA can be used in treatment of the fetal neuroendocrine dysfunctions.

Oxidative stress impact on growth hormone secretion in the eye.

AimTo evaluate the influence of oxidative stress on extrapituitary growth hormone (GH) secretion in the eye and to analyze the interdependence between eye and serum GH levels under normal and hypoxic conditions.MethodsPars plana vitrectomy (PPV) was performed in 32 patients with developed proliferative diabetic retinopathy (PDR) and 49 non-diabetic controls, both of whom required this procedure as part of their regular treatment in the period from April 2013 to December 2014. During PPV, vitreous samples were taken and blood was simultaneously collected from the cubital vein. GH levels in serum and vitreous samples were measured by electrochemical luminescence assay. Oxidative stress was measured by enzyme-linked immunosorbent assay of advanced oxidation protein products (AOPP) and lipid hydroperoxide (LPO) in serum and vitreous.ResultsSerum AOPP levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group) and LPO levels were significantly higher only in PDR group (P < 0.001). There was a significant positive correlation between serum and vitreous LPO levels in PDR group (r = 0.909; P < 0.001). Serum GH levels were significantly higher than vitreous levels in both groups (P < 0.001 for each group). Serum GH levels were significantly higher in PDR group than in controls (P = 0.012). Vitreous GH values were slightly higher in PDR group, but the difference was not significant.ConclusionOur study confirms that GH production in the eye is autonomous and independent of oxidative stress or pituitary GH influence.

The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice

Muscle- and liver-derived IGF-1 play important roles in muscle anabolism throughout growth and aging. Yet, prolonged food restriction is thought to increase longevity in part by lowering levels of IGF-1, which in turn reduces the risk for developing various cancers. The dietary factors that modulate IGF-1 levels are, however, poorly understood. We tested the hypothesis that the adipokine leptin, which is elevated with food intake and suppressed during fasting, is a key mediator of IGF-1 levels with aging and food restriction. First, leptin levels in peripheral tissues were measured in young mice fed ad libitum, aged mice fed ad libitum, and aged calorie-restricted (CR) mice. A group of aged CR mice were also treated with recombinant leptin for 10days. Later, aged mice fed ad libitum were treated with saline (VEH) or with a novel leptin receptor antagonist peptide (Allo-aca) and tissue-specific levels of IGF-1 were determined. On one hand, recombinant leptin induced a three-fold increase in liver-derived IGF-1 and a two-fold increase in muscle-derived IGF-1 in aged, CR mice. Leptin also significantly increased serum growth hormone levels in the aged, CR mice. On the other, the leptin receptor antagonist Allo-aca did not alter body weight or muscle mass in treated mice compared to VEH mice. Allo-aca did, however, produce a significant (20%) decline in liver-derived IGF-1 as well as an even more pronounced (>50%) decrease in muscle-derived IGF-1 compared to VEH-treated mice. The reduced IGF-1 levels in Allo-aca treated mice were not accompanied by any significant change in growth hormone levels compared to VEH mice. These findings suggest that leptin receptor antagonists may represent novel therapeutic agents for attenuating IGF-1 signaling associated with aging, and could potentially mimic some of the positive effects of calorie restriction on longevity.

Düşük Insulin-Like Growth Factor-1 düzeyleri olan bir akromegalik hasta: IGF-1 akromegali tanısında her zaman yüksek bulunmayabilir

The diagnosis of acromegaly is based on demonstration of excess growth hormone (GH) and Insulin-Like Growth Factor-1 (IGF-1) secretion. IGF-1 is the most reliable biochemical indicator of activity of acromegaly. However, there are some pitfalls in the interpretation of change of plasma IGF-1 levels. We aim to report a case with acromegaly that has low IGF-1 levels and elevated GH levels associated with poorly controlled type 2 diabetes mellitus and malnutrition. A 38-years-old woman was admitted to emergency departmant due to hyperglycemia, weakness, cough, dyspnea, high fever. She has been complaining for enlargement of her hands and feet for ten years and she was cachectic for a long time. During oral glucose tolerance test (OGTT), serum growth hormone levels were found to be higher than normal range according to the matching age and sex subjects but IGF-1 and IGFBP-3 levels were measured lower than the reference range. A macroadenoma of 3x2.5 cm diameter was determined in magnetic resonance imaging of the pituitary gland. As a conclusion, determining elevated IGF-1 levels are very important for the diagnosis and activity of acromegaly, but careful interpretation of IGF-1 levels is necessary in type 2 diabetic patients with acromegaly. Key Words: Acromegaly, IGF-1, malnutrition, type 2 diabetes mellitus.

Hyperprolactinemia has no effect on plasma ghrelin levels in patients with prolactinoma.

Accumulating evidence suggests that prolactin is a modulator of body weight and composition and that it regulates some transporters in adipose tissue. It was demonstrated that hyperprolactinemia is associated with weight gain and obesity. Ghrelin is a novel hormone secreted from many organs including the pituitary gland. Ghrelin acts by regulating energy homeostasis and stimulating appetite. The aim of this study is to investigate whether ghrelin has a role in the case of weight gain in patients with prolactinoma. Forty-four patients with prolactinoma, both newly diagnosed and undergoing cabergoline treatment, were included in this study. Age- and sex-matched healthy subjects were included in the control group. Serum fasting glucose, insulin, lipid profile, and ghrelin levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was also calculated. Body mass index (BMI) and total fat ratio (%) of all the participants were assessed by bioelectrical impedance analysis using TBF-310GS™ (Tanita Corporation, Tokyo, Japan). Patients with prolactinoma demonstrated significantly higher serum levels of fasting insulin, triglyceride, and waist and hip circumference measurement. No significant difference was found between the fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and HOMA-IR levels. BMI was significantly higher in the patients with prolactinoma than that in the control group (p<0.05). Additionally, the total body fat percentage was higher in the patients with prolactinoma than that in the control group; however, the difference was not significant (p>0.05). Furthermore, there was no significant difference in terms of the ghrelin levels between these groups. There was a correlation with serum ghrelin and growth hormone levels (p<0.02, rho=0.489). However, no significant correlation was obtained between serum prolactin or ghrelin levels and body fat percentage. According to the results of our study, ghrelin has no effect on weight gain in patients with prolactinoma. Further studies are needed to evaluate whether ghrelin affects the prevalence of obesity in patients with prolactinoma.

Thyroid hormone and estrogen regulate exercise-induced growth hormone release.

Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response.