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The article reviews the sources of scientific literature on the role of somatomedin - insulin-like growth factor-1 (IGF-1) in predicting the development of metabolic disorders in patients with hypertension, the depth of the search for a period of 10 years. It is noted that this scientific problem has been studied in different countries, the connection between IGF-1 deficiency and the occurrence of metabolic disorders in patients with hypertension (AH) is considered to be one of the predictors of cardiovascular disease. It was experimentally established that the study of the content of IGF-1 in the blood revealed a significant decrease in the level of somatomedin in groups of patients with varying degrees of hypertension. Studies have confirmed the pathogenetic role of IGF-1 deficiency in the development of left ventricular hypertrophy and heart failure in patients with hypertension in combination with type 2 diabetes mellitus (DM). It is the deficiency of IGF-1 in the blood was associated with the development of degenerative processes. Immune-modulating ability of IGF-1 has been established, antithrombotic and antiremodeling properties of somatomedin have been proved. It was found that people with normal blood pressure and people without signs of impaired glucose tolerance had significantly higher levels of IGF-1 in the blood. It is established that the study of the role of IGF-1 in the prediction of metabolic disorders in patients with hypertension is a promising scientific problem.

Growth hormone (GH) promotes growth and development in children and is the meaningful co-regulator of the metabolism in adulthood. GH may act directly, through its receptor (GHR), as well as via mediators – insulin-like growth factors: IGF-1, i.e. somatomedin C and IGF-2. Moreover, GH and two growth factors are involved in the mechanisms of cell proliferation, differentiation and survival, hence their oncogenic potential is propounded. Indeed, GH, somatomedins and their receptors are found abundantly in normal and cancer cells in several tissues. It has been shown in animal and human trials that polymorphisms and mutations that increase signal transmission from the GH and IGF-1 receptor are associated with more frequent tumors development and reduce life expectancy. Numerous epidemiological studies have confirmed a clear relationship between GH/IGF-1 level in circulation and a cancer-dependent morbidity and mortality. It dictates caution in case of treatment with use of growth hormone. Such replacement therapy is recommended in cases of GH deficiency. In the common opinion of scientific societies such treatment is generally safe, although in some cases unambiguous opinion in this field cannot be determined yet. On the other hand, on the basis of available evidence, GH cannot be recommended for use by the healthy elderly (ani-aging medicine), bearing in mind that GH decline with age may represent a beneficial adaptation to ageing. Understanding the molecular mechanisms by which GH and GH-dependent growth factors affect cell metabolism and proliferation will allow to use them in oncology in the future.

Background PrePubertal children with type 1 diabetes mellitus are shorter than their non- diabetic peers. we aimed to evaluate the role of HbA1c and IGFBP-3 in this phenomenon. Aim of the work: The aim of the study was to evaluate the effect of glycemic control on the growth and IGFBP-3, represented by height, weight, height and weight percentiles for age in a sample of prepubertal Egyptian children with T1DM. Patients and Methods This study was a cross sectional study conducted on 80 pre-pubertal Egyptian children, divided into 25 Males and 25 Females with T1DM and 30 age matched controls (15 Males and 15 Females), the participants were recruited from the Outpatient Clinic of the Pediatric Department of Ain Shams University Hospitals and the National Institute of Diabetes and Endocrinology in Cairo, Egypt during the period from July 2018 to August 2019. Anthropometric measures including height and weight were obtained and used to calculate the height and weight percentiles using the CDC calculators. HbA1c as well as IGFBP-3 levels were tested. Results The mean age (years) of the participants was (9.671±2.24) for male patients, (9.22 ± 2.19) for female patients and (8.39 ± 2.034) for controls. The height found to be lower in the children with T1DM when compared to the disease-free controls with median values of (129.287 ± 13.410) in male patients, (127.727 ±10.155) in female patients and (136.760 ± 13.431) in the controls. the height and weight percentiles (%) were found to be lower in the children with T1DM when compared to the disease-free controls, the height percentile with median values of 14.54 (IQR 27.95) in male patients, 17.93 (IQR 29.20) in female patients and 87.07 (IQR 20.48) in the controls. the weight percentile with median values of 40.68 (IQR 40.83) in male patients, 30.64(IQR 35.59) in female patients and 85.18 (IQR 20.17) in the controls. A negative correlation between HbA1c (%) and serum IGFBP-3 (ng/ml), height and height percentile were found with (0.014, 0.049 and 0.012) as well as a positive correlation between serum IGFBP-3 and height, height and weight percentiles (%), were found with (,0.004, 0.009 and 0.005 respectively). Serum IGFBP-3 levels were also found to be significantly lower in patients (P < 0.001) with a mean value of (198.6 ± 45.335) in male patients and (168.4 ± 44.317) in female patients and (285.333 ± 61.936) in the disease-free controls. Conclusion Serum IGFBP-3 levels (ng/ml) as well as growth are negatively affected in prepubertal children with T1DM in relation to the glycemic control.

Dear Editor,We report our work on the association of two important biomarkers (serum Insulin-like growth factor −1(IGF-1) and human growth hormone (HGH) with adverse outcomes in kidney transplant r...

Objective The neuroendocrine response to critical illness is dichotomous as it is adaptive during the acute phase then transitions to maladaptive as critical illness becomes prolonged in 25-30% of patients. Presently, monitoring all critically ill patients for endocrinopathies is not the standard of care. However, given the negative impact on patient prognosis, a need to identify those at risk for endocrinopathies, may exist. Thus, a screening tool to identify endocrinopathies along the somatotroph and gonadal axes in a cardiothoracic surgery population was developed. Methods A prospective observational pilot study was conducted in two cardiothoracic surgery intensive care units (ICU) within a multi-site healthcare system. Total testosterone and somatomedin C levels were obtained from 20 adult patients who remained in the ICU for greater than seven days after cardiothoracic surgery and were tolerating nutrition, had a risk of malnutrition and a mobility score of moderate to dependent assistance. Results Twenty patients were included for descriptive analysis (seven females). Thirteen patients tested low for total testosterone, with males more likely to have a testosterone-related endocrinopathy as compared to females (100% vs. 0 to 43%, p = 0.0072). A higher proportion of low somatomedin C levels was found in females than males (57% vs. 31%); however, the difference was not statistically significant (p = 0.251). Conclusions The screening tool used in this pilot study accurately predicted low total testosterone in all men and reasonably predicted low somatomedin C in a majority of women. However, the ability of the tool to predict low total testosterone in women and low somatomedin C in men is less certain. A gender-specific screening tool might be necessary to predict hormonal deficiencies.

Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.

The problems of aging women both in the world and in our country are becoming increasingly relevant. The sharp increase in the incidence among women of the age category, which coincides with the age of menopause, is a serious argument for considering this period and the associated changes as one of the priorities of modern medicine. Already today, despite the general tendency to aging of the population, a third of the life of the majority of women falls on the post-menopausal period, which acquires a special social and even state significance. However, these changes begin at a younger age, which requires close attention of specialists, because it is at this stage that the development of long-term programs to preserve both the reproductive and the general health of the female population is important. The article considers modern views on the problem of ovarian function diminishing in perimenopause and the problem of aging in general. Reproductive and biological age markers and hormonal disorders causing clinical manifestations of perimenopause are given. Attention is paid to the definition of psychological age, its influence on the psychological status of a woman whose passport age is over 40 years old, which coincides with the peak of her professional and social activities. Analyzed modern views on improving the quality of life of women who are in the perimenopausal period. Currently, there are many methods for timely assessment of disorders in systems and organs that can provoke the occurrence of age-related diseases. Therefore, the task of modern medicine is to prevent early aging and introduce preventive methods that improve the quality of life and increase its duration. As the authors of the article note, the assessment of biological and reproductive age is important for the prevention of diseases that can be avoided by following simple guidelines for optimizing lifestyle.

Multiplication-stimulating activity (MSA) produced by Buffalo rat liver cells (BRL-3A) in culture is related to the somatomedin family of growth regulatory polypeptides. MSA will stimulate glucose transport and DNA synthesis in normal chicken embryo fibroblasts (CEF) at concentrations of 10-200 ng/ml. MSA found in BRL-3A-conditioned medium, like the somatomedins in serum, does not exist as the free hormone but is bound to a specific high molecular weight carrier protein. In this report we demonstrate that purified MSA carrier protein (MCP) inhibits the biological activity of MSA on CEF as measured by the stimulation of glucose transport and DNA synthesis. In addition, purified MCP competitively inhibits the binding of 125I-labeled MSA to these cells. In control experiments in which insulin was used as the mitogenic agent, MCP had no effect on these biological responses. These results indicate that the inhibitory effect of MCP is the result of specific interaction with MSA and support the hypothesis that cells may be unresponsive to somatomedins bound to their serum carrier proteins.

The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily among endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of theIgf1andIgf2genes in temporal and spatial manners. The GH/IGF axis, acting in an endocrine and autocrine/paracrine fashion, is the major axis controlling skeletal growth. Studies in rodents have clearly shown that IGFs regulate bone length of the appendicular skeleton evidenced by changes in chondrocytes of the proliferative and hypertrophic zones of the growth plate. IGFs affect radial bone growth and regulate cortical and trabecular bone properties via their effects on osteoblast, osteocyte and osteoclast function. Interactions of the IGFs with sex steroid hormones and the parathyroid hormone demonstrate the significance and complexity of the IGF axis in the skeleton. Finally, IGFs have been implicated in skeletal aging. Decreases in serum IGFs during aging have been correlated with reductions in bone mineral density and increased fracture risk. This review highlights many of the most relevant studies in the IGF research landscape, focusing in particular on IGFs effects on the skeleton.

Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay. Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p

Background and Objectives: Most athletes suffer from zinc and magnesium deficiency. Zinc and magnesium deficiency can reduce anabolic hormones and reduce performance of athletes. The aim of this study was to evaluate the effect of three months of zinc-magnesium supplementation along with intense endurance training on somatomedin C levels and endurance performance in female Wistar rats. Methods: In this experimental study, 24 mature female Wistar rats, were randomly divided into three groups of 8 each: (control, intense endurance training, and intense endurance training+zinc-magnesium supplementation(. The training protocol consisted of running on treadmill for 3 months (5day/week). In the supplement group, in addition to standard meal and water, 227 mg of zinc sulfate and 10g of magnesium sulfate, were used per liter of water. One week before the end of the period, the subjects' endurance performance, was assessed, and 24 hours after the last training session and after 8 hours of overnight fasting, blood samples were collected. Then, plasma level of somatomedin C, was measured. Data were analyzed using one-way ANOVA and Tukey's post hoc tests. Results: In this study, three months of endurance training along with supplementation, had no significant effects on serum somatomedin C levels of the groups (p=0.23), but endurance performance of the endurance training+supplementation group, significantly increased compared to the control (p=0.00) and training without supplementation group (p=0.00). Also, the endurance performance of the training without supplementation group, significantly increased compared to the control group (p=0.003). Conclusion: According to the results, zinc-magnesium supplement may be cautiously taken into account as a factor in improving endurance performance in female rats. &nbsp

As the most trait of commercial fish, increasing the growth rate of skeletal muscle is of great significance to aquaculture industry. However, the regulation of growth hormone/somatomedin (GH/IGF) growth-axis on skeletal muscle has not been effectively applied for many years, and its effect on fish and production significance for aquaculture need to be further studied. This study investigated the regulatory mechanism in sturgeon development and combined multiple organ transcriptomics revealed some common pathways emerged in the developed sturgeon including “Cytokine-cytokine receptor interaction”, “Focal adhesion”, and “Arginine and Proline Metabolism”, while many specific pathways have also been enriched in each organ. Further, all annotated GH/IGF growth-axis related genes were higher in 12 months post-fertilized sturgeon than in 24 months one, showing the potential regulation of GH/IGF growth-axis in sturgeon growth. Besides, we found that our developed hybrid F1 sturgeons with Acipenser baeri♀ and Acipenser schrenckii♂ were highly expressed in downstream of GH/IGF growth-axis than that of A. schrenckii F1 and obviously higher than A. baeri F1. The hybrid F1 with high GH/IGF growth-axis expression and high myofiber diameter also has higher growth performance. The implementation of this study proved the promotion of GH/IGF growth-axis gene on sturgeon growth, which provided a target for further development of commercial fleshy varieties in the future.

There is a growing body of evidence indicating that patients with adult GH deficiency (GHD) are characterized by a cluster of traditional and emerging cardiovascular risk factors and markers, which can significantly increase their cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Patients with adult GHD present multiple different cardiovascular abnormalities. In addition, cardiovascular risk in adult GHD is increased due to altered body composition, abnormal lipid profile, insulin resistance and impaired glucose metabolism. Cardiovascular risk factors can be reversed, at least partially, after GH replacement. However, evidence on the effects of GH replacement on cardiovascular events and mortality is too limited in adult GHD patients. Aim of this review is to provide an at-a-glance overview of the role of the GH/IGF-I on the cardiovascular system and the state of art of the effects of GH replacement on cardiovascular system.

The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depressive symptoms, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of age's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). 22 serum proteins were recognized as partial mediators of age's association with δ. These include Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2), which we had previously associated with age-specific cognitive change, and both Pancreatic Polypeptide (PP) and von Willebrand Factor (vWF), previously associated with δ. Nine other δ-related proteins were not confirmed by this ethnicity adjusted analysis. Our findings suggest that age's association with the disabling fraction of cognitive performance is partially mediated by serum proteins, somatomedins and hormones. Those proteins may offer targets for the specific treatment of age-related effects on dementia severity and conversion risk.

The current understanding of human growth hormone (hGH; here GH) action is that the molecule is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. It can be classified as a protein (comprising more than 50 amino acids) but true proteins have tertiary and quaternary chains creating a more complex structure, hence GH is usually classified as a polypeptide. GH is normally secreted at night during sleep and promotes skeletal, visceral and general body growth through the action of somatomedins or IGFs, notably IGF-1. In some tissues, GH action is directed via specific receptors GHRs; these are most abundant in liver, adipose and muscle tissues but have also been shown in granulosa cells, testicular tissues and on the oocyte, as well as in glandular cells of the luteal phase endometrium and decidua; such findings being recent and minimally researched to now. Following engagement with its receptor, the transduction process activates multiple signaling proteins. These all lead to extensive metabolic and mitogenic (growth promoting) responses. Clinically, GH is known to have an important role in pubertal development and is a key hormone for the vigor associated with adolescence and early adult life stages but has a faded presence and role for later adulthood, beyond age 30 years, and is minimally detected in advanced age, beyond 40 years. In association with the rapidly increasing trend for delaying reproduction beyond age 35 years, GH is being widely researched now as a potential adjuvant for infertility treatment in this group who, studies consistently show, have a poorer prognosis than younger females when relying on autologous oocytes. The idea that the age-related reduction in fertility prognosis is a feature of growth hormone deficiency is supported by our studies showing an elevated binding protein IGFBP-3/IGF-1 ratio and this can be reduced to a normal range (matching younger, good prognosis women) by the administration of GH as an adjuvant.

Aim: Many studies have examined the effects of different calciotropic hormones on fracture healing, whereas few studies focus on growth factors. Local detection of somatomedin C (IGF-1) in fracture callus, application of growth hormone (GH) and IGF-1 as non-union treatment, and low GH and IGF-1 levels in osteoporotic fractures indicate that these hormones are effective in fracture healing. However, most of these studies are based on post fracture GH and IGF-1 levels. GH and IGF-1 are also involved in acute phase response and can change due to trauma. The aim of this study is to investigate the change in GH and IGF-1 levels in patients treated with osteotomy, in which an iatrogenic fracture is created, and to evaluate the effect of these hormones on fracture healing by comparing the results before and after the fractures. Methods: Patients who were diagnosed with developmental dysplasia of the hip and underwent surgery between 2014-2015 were prospectively followed for this cohort study. Forty-one patients were included, and two groups were formed. Patients who underwent open reduction and soft tissue release without osteotomy (n=20) were included in the first group. Patients who underwent pelvic osteotomy (n=21), in which iatrogenic fractures were created, were included in the second group. Blood samples were obtained from all patients pre-operatively and on the 1st and 28th postoperative days. Friedman and Mann-Whitney U tests were used for statistical analysis. Results: Mean age of the first group, comprising 19 females (95%) and 1 male (5%), was 11.25 months (Range: 6-25 months). Mean age of the second group, including 17 females (85.7%) and 4 males (14.3%), was 74.4 months (Range: 24-120 months). While there was no significant difference between pre- and postoperative GH values in the first group (P=0.05), postoperative GH levels were significantly higher than preoperative GH levels in the second group (P

OBJECTIVES: Maternal obesity is strongly associated with offspring obesity risk. However, studies show that paternal obesity also affects offspring phenotype, especially in males. Programming of the growth hormone (GH) insulin-like growth factor (IGF) axis seems to be an important mechanism in this finding, but evidence regarding this relationship in humans is scarce. The primary purpose of this study was to evaluate associations between maternal and paternal adiposity with that of their offspring. A secondary aim was to investigate associations between paternal adiposity with GH levels in male offspring. METHODS: Parent-offspring trios (n = 209) from the Glowing study were studied. Percent body fat mass (%FM) was measured using air displacement plethysmography early in pregnancy in parents, and at age 2 weeks in the offspring. Plasma GH levels were measured at birth from umbilical cord blood (n = 31) and at age 2 years (n = 39) in male offspring. Multiple linear regression was used to model infant's %FM (dependent variable) at 2 weeks of age using parental %FM, race, age, IQ, income, delivery method, gestational weight gain, feeding mode, and gestational age (GA) as independent variables. The best fitted models were constructed for girls and boys. Spearman correlations (ρ) between paternal %FM and offspring GH levels were adjusted for maternal %FM. RESULTS: Girls (n = 94): Paternal %FM did not associate with female newborn %FM. Instead, maternal %FM (β = 0.12, P = 0.010) and C-section delivery mode (β = 2.56, P = 0.011) had the strongest associations with female newborn %FM. Boys (n = 115): Maternal %FM (β = 0.12, P = 0.006) and GA (β = 1.06, P = 0.003) were positively associated with male newborn %FM, whereas paternal %FM was negatively associated (β = −0.09, P = 0.014) with male offspring adiposity. There was no significant correlation between paternal %FM and GH measured at birth (ρ = 0.19, P = NS) in boys. However, at age 2 years, GH levels in boys decreased with increasing paternal %FM (ρ = −0.40, P = 0.015). Maternal %FM did not correlate with offspring GH level at any age. CONCLUSIONS: Parental obesity differentially associates with newborn girls’ and boys’ adiposity at age 2 weeks. In line with prior findings in animal models, this preliminary analysis points to programming of the GH/IGF axis in male offspring born to obese fathers. FUNDING SOURCES: USDA ARS # 6026-51000-010-05S, NIH 1UL1RR029884.

BACKGROUND: Rapid growth of skeletal muscle in the neonate requires the coordination of protein deposition and myonuclear accretion. During this developmental stage, muscle protein synthesis is highly sensitive to amino acid supply, especially Leu, but we do not know if this is true for satellite cells, the source of muscle fiber myonuclei. OBJECTIVE: We examined whether dietary protein restriction reduces myonuclear accretion in the neonatal pig, and if any reduction in myonuclear accretion is mitigated by restoring Leu intake. METHODS: Neonatal pigs (1.53 ± 0.2 kg) were fitted with jugular vein and gastric catheters and fed 1 of 3 isoenergetic milk replacers every 4 h for 21 d: high protein [HP; 22.5 g protein/(kg/d); n= 8]; restricted protein [RP; 11.2 g protein/(kg/d); n= 10]; or restricted protein with Leu [RPL; 12.0 g protein/(kg/d); n= 10]. Pigs were administered 5-bromo-2’-deoxyuridine (BrdU; 15 mg/kg) intravenously every 12 h from days 6 to 8. Blood was sampled on days 6 and 21 to measure plasma Leu concentrations. On day 21, pigs were killed and the longissimus dorsi (LD) muscle was collected to measure cell morphometry, satellite cell abundance, myonuclear accretion, and insulin-like growth factor (IGF) system expression. RESULTS: Compared with HP pigs, postprandial plasma Leu concentration in RP pigs was 37% and 47% lower on days 6 and 21, respectively (P

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity. Late in the post-restraint recovery period, antidepressant-treated animals were significantly heavier and had better bone features than saline-treated controls, when assessed in the distal femoral metaphysis. The propensity to gain weight might have influenced the rate of catch-up growth and bone allometry, as heavier animals treated with fluoxetine also had enhanced bone features when compared to non-stressed animals. Therefore, short-term antidepressant treatment ameliorated the long-term effects of stress on body growth and bone. Growth and bone structural features were associated with leptin levels, and the interaction between leptin levels and antidepressant was significant for bone mineral content, suggesting that short-term antidepressants in the context of long-term diet-induced obesity modified the role of leptin in bone formation. To our knowledge this is the first study reporting that short-term antidepressant treatment has long-lasting effects in restoring the effects of chronic stress in body weight and bone formation. Our findings may be relevant to the understanding and treatment of osteoporosis, a condition of increasing prevalence due to the aging population.

Background: Pituitary adenomas are benign and frequent tumors, some of them with tendency to be recurrent or invasive e. several pituitary tumors are positive for secretion of one or more hormones of the same adenohypophysial cell lineage. However, some cases have a subclinical course and are underestimated because they have plurihormonal secretion of different adenohypophyseal cells lineage. Clinical Case: A 38 years old women with chronic headaches, who is in fertility treatment for 12 month ago presents to the clinic with unremarkable physical examination. Her laboratory studies include: Normal campimetry. T3 (triiodothyronine) 2.15 ng/m L (NR:0.8 - 2.0), TSH (thyroid stimulating hormone) 4.4 uU/mL (NR:0.27 - 4.2), T4 (tetraiodothyronine) 13.54 ug/dl, (NR:5.1 - 14.1), Free T4 2.44 ng/d (NR:0.93 - 1.7), Estradiol 60.2 pg/ml, FSH (Follicle stimulating hormone) 4.3 mUI/ml (NR:1,7-12), Cortisol (?8 am) 9.29 ug/dl (NR:4.2 - 38.4), ACTH (Corticotrophin-releasing hormone) 13.1 pg/ml (NR: 0.0 - 46.0), Somatomedin C (IGF-1) 231 .0 ng/ml (NR for age?: 57.0-241.0). Brain MRI with pituitary protocol showed in T1 an isointense lesion and slightly heterogeneous in T2 in the anterior and left aspect of the turkish saddle, of 1 x 1.1 x 1.1 cm of anteroposterior, transverse and cephalocaudal diameter, suggestive of a macroadenoma. The tumor pathology showed, possitive for a pituitary adenoma. Immunohistochemistry results were negative for: ACTH:, positive for GH, TSH: (+++) and for Prolactin:. Her post-operative findings showed a residual pituitary gland without significant findings. Her post operative pituitary axis include: Sodium 139.2 mmol/l (NR”135.0 - 145.0), Chloride 100.8 mmol/l (NR95.0 - 115.0), Potassium 3.71 mmol/l (NR3.5 - 5.1), ACTH 4.1 pg/ml(NR0.0 - 46.0), Cortisol (am) 11.11 ug/dl (NR4.2 - 38.4), Estradiol 106.5 pg/ml, FSH 5.1 mUI/ml, LH (Luteinizing Hormone) 13.53 mIU/ml, Somatomedin C (IGF-1) 134 .0 ng/m, Free T32.4 pg/ml, TSH 0.9 uU/mL Free T4 0.99 ng/dl, and Prolactin 23.4ng/ml. Patient had a satisfactory clinical course after surgery, she maintained normal pituitary function without requirement of hormonal replacement therapy. Conclusion: We present a a prolactin, TSH and GH secreting pituitary adenoma case, which is very unusual. It i is important to make a proper pituitary evaluation, and offer effective treatment to prevent complications

Regulation of final organ size is a complex developmental process that involves the integration of systemic and organ-specific processes. Previously, we have shown that in developing Drosophila, perturbing the growth of one imaginal disc - the parts of a holometabolous larva that become the external adult organs - retards growth of other discs and delays development, resulting in tight inter-organ growth coordination and the generation of a correctly proportioned adult. Whether different parts of the same imaginal disc similarly coordinate their growth to generate a functioning adult organ is, however, unclear. In this study, we use the wing imaginal disc in Drosophila to study and identify mechanisms of intra-organ growth coordination. We generate larvae in which the two compartments of the wing imaginal disc have ostensibly different growth rates (wild-type or growth-perturbed). We find that there is tightly coordinated growth between the wild-type and growth-perturbed compartments, where growth of the wild-type compartment is retarded to match that of the growth-perturbed compartment. Crucially, this coordination is disrupted by application of exogenous 20-hydroxyecdysone (20E), which accelerates growth of the wild-type compartment. We further elucidate the role of 20E signaling in growth coordination by showing that in wild-type discs, compartment-autonomous up-regulation of 20E signaling accelerates compartment growth and disrupts coordination. Interestingly, growth acceleration through exogenous application of 20E is inhibited with suppression of the Insulin/Insulin-like Growth Factor Signaling (IIS) pathway. This suggests that an active IIS pathway is necessary for ecdysone to accelerate compartment growth. Collectively, our data indicate that discs utilize systemic mechanisms, specifically ecdysone signaling, to coordinate intra-organ growth.

Leptin is an anorexigenic peptide hormone that circulates as an indicator of adiposity in mammals, and functions to maintain energy homeostasis by balancing feeding and energy expenditure. In fish, leptin tends to be predominantly expressed in the liver, another important energy storing tissue, rather than in fat depots as it is in mammals. The liver also produces the majority of circulating insulin-like growth factors (IGFs), which comprise the mitogenic component of the growth hormone (GH)-IGF endocrine growth axis. Based on similar regulatory patterns of leptin and IGFs that we have documented in previous studies on hybrid striped bass (HSB: Morone saxatilis×Morone chrysops), and considering the co-localization of these peptides in the liver, we hypothesized that leptin might regulate the endocrine growth axis in a manner that helps coordinate somatic growth with energy availability. Using a HSB hepatocyte culture system to simulate autocrine or paracrine exposure that might occur within the liver, this study examines the potential for leptin to modulate metabolism and growth through regulation of IGF gene expression directly, or indirectly through the regulation of GH receptors (GHR), which mediate GH-induced IGF expression. First, we verified that GH (50nM) has a classical stimulatory effect on IGF-1 and additionally show it stimulates IGF-2 transcription in hepatocytes. Leptin (5 and/or 50nM) directly stimulated in vitro GHR2 gene expression within 8h of exposure, and both GHR1 and GHR2 as well as IGF-1 and IGF-2 gene expression after 24h. Cells were then co-incubated with submaximal concentrations of leptin and GH (25nM each) to test if they had a synergistic effect on IGF gene expression, possibly through increased GH sensitivity following GHR upregulation by leptin. In combination, however, the treatments only had an additive effect on stimulating IGF-1 mRNA despite their capacity to increase GHR mRNA abundance. This suggests that leptin's stimulatory effect on GHRs may be limited to enhancing transcription or mRNA stability rather than inducing full translation of functional receptors, at least within a 24-h time frame. Finally, leptin was injected IP (100ng/g and 1μg/gBW) to test the in vivo regulation of hepatic IGF-1 and GHR1 gene expression. The 100ng/g BW leptin dose significantly upregulated in vivo IGF-1 mRNA levels relative to controls after 24h of fasting, but neither dosage was effective at regulating GHR1 gene expression. These studies suggest that stimulation of growth axis component transcripts by leptin may be an important mechanism for coordinating somatic growth with nutritional state in these and perhaps other fish or vertebrates, and represent the first evidence of leptin regulating GHRs in vertebrates.

BACKGROUND: Chronic undernutrition, a condition currently affecting more than 17 millions of children under five years of age, has severe long-term consequences including stunting. Epidemiologic studies have emphasized that undernutrition cannot be ascribed to food insecurity alone and gut microbiota has been shown to play an active role in disease aetiology. In mammals, post-natal growth is controlled by the activity of the somatotropic axis. Undernutrition leads to a decrease of the Insulin like Growth Factor 1 (IGF-1) and a state of Growth Hormon (GH) resistance. AIMS: Previously we have shown the capacity of selected Lactobacillus plantarum strain to maintain growth in infant mono-colonized mice during chronic undernutrition. Here we show that L. plantarum retains its growth promoting capabilities also in a conventional mouse model. METHODS: C57BL6 male mice were weaned at 21 days and bred on a standard or an experimental (isocaloric, hypoprotidic and hypolipidic) diet until young adulthood. One group of mice on experimental diet received an Lp(WJL) oral supplementation (2*10^8 CFU/day; 5 days per week) and the other group received placebo. Length and weight were measured weekly. Mice were sacrificed at day 56 to study the impact of the Lp(WJL) oral supplementation on IGF-1 levels and organ growth. Somatotropic axis activity was tested at Day 28 by injecting the mice with GH and measured by the STAT5 phosphorylation level. RESULTS: At D56, mice fed with the experimental diet were smaller than the standard diet group (7.7 vs 8.9 cm; p< 0.01). Undernourished mice had a lower hepatic level of IGF-1 (113 ± 39 vs 174 ± 35 pg/mg tissues; p

Thyroid cancer (TC) is the most common endocrine tumor. Although the majority of TCs show good prognoses, a minor proportion are aggressive and refractory to conventional therapies. So far, the molecular mechanisms underlying TC pathogenesis are incompletely understood. Evidence suggests that TC cells and their precursors are responsive to insulin and insulin-like growth factors (IGFs), and often overexpress receptors for insulin (IR) and IGF-1 (IGF-1R). IR exists in two isoforms, namely IR-A and IR-B. The first binds insulin and IGF-2, unlike IR-B, which only binds insulin. IR-A is preferentially expressed in prenatal life and contributes to development through IGF-2 action. Aggressive TC overexpresses IR-A, IGF-2, and IGF-1R. The over-activation of IR-A/IGF-2 loop in TC is associated with stem-like features and refractoriness to some targeted therapies. Importantly, both IR isoforms crosstalk with IGF-1R, giving rise to the formation of hybrids receptors (HR-A or HR-B). Other interactions have been demonstrated with other molecules such as the non-integrin collagen receptor, discoidin domain receptor 1 (DDR1), and the receptor for the hepatocyte growth factor (HGF), Met. These functional networks provide mechanisms for IR signaling diversification, which may also exert a role in TC stem cell biology, thereby contributing to TC initiation and progression. This review focuses on the molecular mechanisms by which deregulated IR isoforms and their crosstalk with other molecules and signaling pathways in TC cells and their precursors may contribute to thyroid carcinogenesis, progression, and resistance to conventional treatments. We also highlight how targeting these alterations starting from TC progenitors cells may represent new therapeutic strategies to improve the clinical management of advanced TCs.

Background and Aims: Interest in growth hormone (GH) is inextricably linked to the need for in depth understanding of the somatomedins (insulin-like growth factors) which are polypeptides structurally similar to insulin and with broad physiological activity. To date, the most commonly known is Insulin-Like Growth Factor I (IGF-I). Despite considerable current knowledge of IGF-I, however, its bioactivity is incompletely understood. Measurement of IGF-I is of the utmost importance in the diagnosis and treatment of, for example acromegaly and growth hormone deficiency. The development of recombinant IGF-I, has allowed its use in such cases. Clinical practice, however, shows that few young/adult patients will benefit from treatment with the rIGF-I, mecasermin, given the number of adverse effects found. This review focuses on current knowledge mainly related to IGF-I and the use of its recombinant form (rIGF-I) in clinical practice. Several functions of IGI-II have been elucidated but their clinical significance is unclear.

The purpose of the present study was to determine the response of glucose (G), insulin (In) and insulin-like growth factor (IGF)-I to eccentric (ECC) vs. concentric (CON) resistance exercise in healthy trained and untrained subjects. Venous blood samples were drawn before and immediately after the test, and during 1-hour recovery for the determinations of hormonal and somatomedin concentrations. As compared to resting values, the maximal eccentric (ECC) resistance exercise test caused a significant decrease in G level (p

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia with a wide variety of solid tumors. It is considered to cause hypoglycemia by increasing the insulin-like bioactivity of the circulating insulin-like growth factor (IGF) system, however, the precise mechanism of hypoglycemia remains unclear. In this manuscript, we report on a patient suffering from NICTH caused by a small cell carcinoma of the colon. This is the first report focusing on the role of bioactive IGFs for this pathological condition. First, we demonstrated that the IGF signal pathway has been activated in this tumor in an autocrine and/or paracrine manner using immunohistochemical analysis. Second, we confirmed that bioactive IGFs in the patient's serum were increased using a modified kinase receptor activation assay, thus bioactive IGFs (mainly IGF-2) could be considered to play a major pathogenic role in enhanced hypoglycemic insulin-like activity. Third, increased IGF bioactivity in the patient's serum was completely inhibited by an anti-IGF neutralizing antibody in vitro. These results suggest that neutralization of bioactive IGFs might become a novel therapeutic strategy for NICTH to relieve the hypoglycemic symptoms together with the tumor suppressive effect.

Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population.Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS).1,233 elderly participants from the CHS and SHHS.The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p0.01). As expected, slow wave sleep was better preserved in females compared to males (22% total sleep time vs. 9% total sleep time, p0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] ≥ 5/h) was more prevalent in males compared to females (60% vs. 46%, p0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI ≥ 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI ≥ 5 and15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and also the one with the highest mortality rate. Tumor growth is assisted by various growth factors, and insulin-like growth factors (IGFs) are among the most important. A majority of the IGFs are bound to IGF-binding proteins (IGFBPs) and their release is dependent on the rate of IGFBP proteolysis. The action of free IGFs is exerted and controlled by binding to cell membrane receptors (IGF-Rs). The objective of this work was to connect two determinants of the CRC pathology: oxidation as a process that underlies tumor development and the members of the IGF system that control it. Carbonyl groups (CO) on IGFBP-2, IGFBP-3, IGF-1R, and IGF-2R were determined in samples obtained from patients with CRC, and IGF-binding properties of these proteins were analyzed. According to our results, IGFBP-2 and IGFBP-3 in serum had increased content of CO groups due to CRC. Oxidation of IGFBP-2 increased its affinity for IGF molecules, whereas oxidation of IGFBP-3 reduced it. As for receptors, only intact CO-IGF-2R was detected on solubilized colon membranes, whereas CO-IGF-1R was degraded into fragments. Oxidative changes in the IGF axis may be regarded as part of the mechanism of its action. IGFs bound to IGFBP-3 remain in the circulation, whereas those bound to IGFBP-2 freely reach target tissues. Therefore, oxidation supports IGF distribution toward tissues and, consequently, promotes tumor growth.

Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice.

BackgroundAcromegaly is an illness usually defined by excessively high growth hormone (GH) and insulin like growth factor 1 (IGF-1) levels, the latter mainly reflecting GH action on the liver. IGF-1, also known as somatomedin C, mediates several actions of GH. The diagnosis and management of acromegaly is relatively straight forward, but long-term follow-up of patients can be difficult, as elevated IGF-1 levels can occur in the presence of apparently normalised GH levels and late recurrence of acromegaly may arise despite previous suppression on oral glucose tolerance testing. Data suggest this applies especially to patients in whom the GH receptor lacks exon 3. In such patients, GH may not always be a useful marker of disease, and traditional GH cut-offs may be misleading. Recent data suggest that soluble Klotho (sKlotho), besides and in addition to IGF-1, may help monitor the activity of GH-producing adenomas (presumably reflecting GH action on the kidneys) and may be a useful supplementary tool.MethodsGHR genotyping was performed in 112 patients with acromegaly. IGF-1 and sKlotho levels were measured in the sera of patients before and after transsphenoidal surgery, with emphasis on patients judged inconclusively cured by surgery or with small residual tumour masses shortly after surgery. Patients were assessed for recurrence of acromegaly with GH levels (random or nadir during an oGTT).ResultsOf the 48 patients who underwent surgery between 2000 and 2009 and who had well-documented longer term follow-up at our institution, 29 had no biochemical evidence of residual disease activity after transsphenoidal surgery (marked reduction in IGF-1 and sKlotho levels, GH suppressible to

Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.