Role Of Hormones Research Articles

Role of 25 hydroxyvitamin d and PTH in chronic renal failure: new targets and new therapies

Suboptimal levels of 25 hydroxyvitamin D (25OHD) are common in haemodialysis patients (CKD-5D) and may be associated with reduced muscle strength, increased falls risk and fractures. Reasons for suboptimal 25OHD in CKD-5D will be explored in this presentation and the association between 25OHD, 1,25 dihdroxyvitamin D, PTH and renal function will be examined. The increased risk of hip fracture in dialysis patients will be demonstrated and data exploring the hypothesis that 25OHD levels may be independently associated with falls risk in CKD-5D will be examined. Whilst supplementation with calcium and cholecalciferol reduces hip and other non-vertebral fractures in elderly individuals, in part attributable to reduction in falls, the relationship between 25OHD and falls risk has not been investigated in CKD-5D in the past. Consequently, in addition to the traditional endocrine role for vitamin D, that requires renal conversion of 1,25 (OH) 2 D, circulating levels of 25OHD may play a more important and direct auto/paracrine role in muscle metabolism, both in people with normal renal function and those on dialysis.

Cold exposure and adipose nitric oxide and mast cells: influence on aorta contractility

Both nitric oxide (NO) and mast cells play important roles in adipose and vascular tissue biology. Chronic cold stress decreases the sensitivity of vascular smooth muscle to various contractile agents including norepinephrine (NE). In our previous cold exposure study we found that the contractile response of isolated rat aortas to NE was significantly reduced, and the number of rat aortic adventitial mast cells decreased. Histologically and functionally, white and brown adipose tissue (WAT and BAT) can be distinguished. Beyond its significance in energy store/release and heat production, adipose tissue secretes multiple signaling molecules that have endocrine and paracrine role in the regulation of vascular functions. The aims of the present study were to examine chronic cold exposure-induced alterations in (i) the concentration of NO released from selected regions of WAT and BAT in female and male rats, (ii) the histochemistry of white and brown adipose mast cells, and (iii) whether adipose-derived NO affects the contraction of isolated rat aorta to NE. Twelve females and 12 males Spraque-Dawley rats (150-200 g body weight) were used. The rats were exposed to a cold/freely moving stress for 2 hours each day for 5 consecutive days. At the end of cold exposure, the rats were sacrificed, and samples of thoracic aorta with associated periadventitial adipose tissue (tunica adiposa) were obtained. WAT and BAT were isolated from subcutaneous abdominal and interscapular areas, respectively. The concentration of NO was measured by capillary electrophoresis and mast cells were evaluated histochemically. The response of aorta smooth muscles to NE was recorded in the isolated organ bath. To determine whether adipose-derived NO affects aorta contraction to NE, cumulative dose response curves to NE (10 -8 -10 -3 M) were obtained with or without isolated WAT/BAT suspended in the organ bath medium. In control animals, a gender-related significant difference in NO production in both WAT and BAT was found, NO levels being significantly higher in female than male rats. Data from the contractile response of isolated aorta to NE suggest that receptor affinity to NE is significantly different between female and male controls. Presence of BAT and WAT (isolated from cold-exposure animals) in the bath changed the response of aorta smooth muscle to NE. Displaying a gender dimorphism, BAT/WAT-derived NO, or other vasorelaxing factors, seem to reduce receptor density and/or affinity to NE. Adipose mast cell histochemistry also showed diversity in respect to subtype, gender, and cold exposure. Altogether, we found (i) a gender difference in adipose-released NO and in adipose mast cell histochemistry to cold exposure, and (ii) peripheral adipose tissues affect aortic contractile responses to NE likely by a NO-mediated pathway during cold exposure, suggesting that adipose tissue may limit cold-induced excessive vasoconstriction. Our ongoing study aims at the evaluation of whether aortic tunica adiposa itself could also contribute to this phenomenon. Adipobiology 2009; 1: 67-75.

The peptide hormone pQDLDHVFLRFamide (crustacean myosuppressin) modulates theHomarus americanuscardiac neuromuscular system at multiple sites

pQDLDHVFLRFamide is a highly conserved crustacean neuropeptide with a structure that places it within the myosuppressin subfamily of the FMRFamide-like peptides. Despite its apparent ubiquitous conservation in decapod crustaceans, the paracrine and/or endocrine roles played by pQDLDHVFLRFamide remain largely unknown. We have examined the actions of this peptide on the cardiac neuromuscular system of the American lobster Homarus americanus using four preparations: the intact animal, the heart in vitro, the isolated cardiac ganglion (CG), and a stimulated heart muscle preparation. In the intact animal, injection of myosuppressin caused a decrease in heartbeat frequency. Perfusion of the in vitro heart with pQDLDHVFLRFamide elicited a decrease in the frequency and an increase in the amplitude of heart contractions. In the isolated CG, myosuppressin induced a hyperpolarization of the resting membrane potential of cardiac motor neurons and a decrease in the cycle frequency of their bursting. In the stimulated heart muscle preparation, pQDLDHVFLRFamide increased the amplitude of the induced contractions, suggesting that myosuppressin modulates not only the CG, but also peripheral sites. For at least the in vitro heart and the isolated CG, the effects of myosuppressin were dose-dependent (10(-9) to 10(-6) mol l(-1) tested), with threshold concentrations (10(-8)-10(-7) mol l(-1)) consistent with the peptide serving as a circulating hormone. Although cycle frequency, a parameter directly determined by the CG, consistently decreased when pQDLDHVFLRFamide was applied to all preparation types, the magnitudes of this decrease differed, suggesting the possibility that, because myosuppressin modulates the CG and the periphery, it also alters peripheral feedback to the CG.

Comparative structure analyses of cystine knot-containing molecules with eight aminoacyl ring including glycoprotein hormones (GPH) alpha and beta subunits and GPH-related A2 (GPA2) and B5 (GPB5) molecules

BackgroundCystine-knot (cys-knot) structure is found in a rather large number of secreted proteins and glycoproteins belonging to the TGFbeta and glycoprotein hormone (GPH) superfamilies, many of which are involved in endocrine control of reproduction. In these molecules, the cys-knot is formed by a disulfide (SS) bridge penetrating a ring formed by 8, 9 or 10 amino-acid residues among which four are cysteine residues forming two SS bridges. The glycoprotein hormones Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Thyroid-Stimulating Hormone (TSH) and Chorionic Gonadotropin (CG) are heterodimers consisting of non-covalently associated alpha and beta subunits that possess cys-knots with 8-amino-acyl (8aa) rings. In order to get better insight in the structural evolution of glycoprotein hormones, we examined the number and organization of SS bridges in the sequences of human 8-aa-ring cys-knot proteins having 7 (gremlins), 9 (cerberus, DAN), 10 (GPA2, GPB5, GPHα) and 12 (GPHβ) cysteine residues in their sequence.DiscussionThe comparison indicated that the common GPH-alpha subunit exhibits a SS bridge organization ressembling that of DAN and GPA2 but possesses a unique bridge linking an additional cysteine inside the ring to the most N-terminal cysteine residue. The specific GPHbeta subunits also exhibit a SS bridge organization close to that of DAN but it has two additional C-terminal cysteine residues which are involved in the formation of the "seat belt" fastened by a SS "buckle" that ensures the stability of the heterodimeric structure of GPHs. GPA2 and GPB5 exhibit no cys residue potentially involved in interchain SS bridge and GPB5 does not possess a sequence homologous to that of the seatbelt in GPH β-subunits. GPA2 and GPB5 are thus not expected to form a stable heterodimer at low concentration in circulation.SummaryThe 8-aa cys-knot proteins GPA2 and GPB5 are expected to form a heterodimer only at concentrations above 0.1 microM: this would be consistent with a short-term paracrine role but not with an endocrine role after dilution in circulation. Consequently, GPA2 and GPB5 could exert separate endocrine roles either during development and/or during adult life of both vertebrates and invertebrates.

The Role of Melatonin in Rheumatic Diseases

Melatonin is a neurohormone that has attracted a great deal of attention, being frequently investigated in recent years. Due to its wide-spectrum of properties, melatonin has been suggested to be effective with respect to the etiology and treatment of several diseases. Its action on the immune system and antioxidant features has brought interest to this hormone's role in chronic inflammatory diseases. Furthermore, the detection of a correlation between the circadian release of melatonin and the rhythmic symptoms and signs of rheumatoid patients has led scientists to address its involvement in rheumatic diseases. Studies with suitable methodologies and broad perspectives are required in order to determine the functions of this neurohormone, whose effects are dependent on its physiological and pharmacological doses.

The Uterine Placental Bed Renin-Angiotensin System in Normal and Preeclamptic Pregnancy

Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angio tensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT1), AT2, and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT2 receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT1 receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia.

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma

Objective Cleavage of IGFBPs by proteases results in IGFBP fragments that have altered IGF-binding affinity, and IGF-independent roles. We have previously purified a specific IGFBP-1 protease activity from the urine of an individual with multiple myeloma and dermatitis. The aim of this study was to determine whether IGFBP-1 protease activity and/or IGFBP-1 fragments were present in the circulation of this patient. Methods The size of immunoreactive IGFBP-1 in serum samples was determined after Superose 12 chromatography. Intact IGFBP-1 and IGFBP-1 fragments were characterized in four RIAs and after SDS–PAGE. Results Specific proteolysis of IGFBP-1 generated an N-terminal fragment (IGFBP-1 1–130) with a predicted molecular mass of 13 kDa but an apparent mass of 21 kDa on SDS–PAGE. A C-terminal fragment (IGFBP-1 131–234) produced in vitro migrated at 11.4 kDa, close to its predicted size. However a C-terminal fragment of cleaved IGFBP-1 (IGFBP-1 142–234) migrated at 14 kDa on SDS–PAGE. Serum from the patient inhibited IGFBP-1 protease activity. Immunoreactive IGFBP-1 in patient serum was present at molecular masses consistent with IGFBP-1 fragments, in addition to intact IGFBP-1. Conclusions Specific cleavage of IGFBP-1 occurs at the tissue level and not in the circulation in a patient with multiple myeloma and dermatitis. The fragments that are generated may have endocrine roles.

Stimulation of incretin secretion by dietary lipid: is it dose dependent?

After the ingestion of nutrients, secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) by the enteroendocrine cells increases rapidly. Previous studies have shown that oral ingestion of fat stimulates secretion of both incretins; however, it is unclear whether there is a dose-dependent relationship between the amount of lipid ingested and the secretion of the hormones in vivo. Recently, we found a higher concentration of the incretin hormones in intestinal lymph than in peripheral or portal plasma. We therefore used the lymph fistula rat model to test for a dose-dependent relationship between the secretion of GIP and GLP-1 and dietary lipid. Under isoflurane anesthesia, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single, intraduodenal bolus of saline or varying amounts of the fat emulsion Liposyn II (0.275, 0.55, 1.1, 2.2, and 4.4 kcal). Lymph was continuously collected for 3 h and analyzed for triglyceride, GIP, and GLP-1 content. In response to increasing lipid calories, secretion of triglyceride, GIP, and GLP-1 into lymph increased dose dependently. Interestingly, the response to changes in intraluminal lipid content was greater in GLP-1- than in GIP-secreting cells. The different sensitivities of the two cell types to changes in intestinal lipid support the concept that separate mechanisms may underlie lipid-induced GIP and GLP-1 secretion. Furthermore, we speculate that the increased sensitivity of GLP-1 to intestinal lipid content reflects the hormone's role in the ileal brake reflex. As lipid reaches the distal portion of the gut, GLP-1 is secreted in a dose-dependent manner to reduce intestinal motility and enhance proximal fat absorption.

The uterine placental bed Renin-Angiotensin system in normal and preeclamptic pregnancy.

Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT(1)), AT(2), and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT(2) receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT(1) receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia.

Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

BackgroundDuring development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone.Methodology/Principal FindingsWe quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68 = 89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM.Conclusions/SignificanceCollectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental amniotes. Rather, we hypothesize that these membranes may share an additional unifying characteristic, steroidogenesis, across amniotes at large.

Human trophoblast differentiation

The role of the placenta in normal and pathological pregnancy is poorly understood, but important new insights into trophoblast biology have been obtained in recent years. The oxygen environment and retroviral envelope proteins are now known to play a role in morphological and functional differentiation of the human trophoblast. The qualitative and quantitative development of trophoblast hormonal functions during pregnancy, from a paracrine role during the first trimester to an endocrine role in placentation and uterine quiescence, is becoming increasingly clear. These findings are offering new perspectives in the diagnosis and treatment of disorders of placental origin.

Study of Omentin1 and Other Adipokines and Hormones in PCOS Patients.

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Recent studies have shown that plasma omentin-1 levels decrease with obesity. Currently, no data exists on the relative correlation between omentin-1 with other adipokines or the expression and regulation of omentin-1 in the serum of women with PCOS. The objective of this study is to evaluate the role of omentin-1 levels or omentin-1 /adipokines ratio in the serum of women with PCOS compared with matched control subjects. The study involved 60 patients with PCOS and 30 women without PCOS who were used as controls. To examine the relationship between fasting serum omentin-1 and serum interleukin-6 (IL-6), interleukin-8 (IL-8), resistin, ghrelin, leptin RBP-4 and tumor necrosis factor-a (TNF-a) levels in infertile PCOS and non-PCOS subjects. Also, insulin and other hormones were measured in both groups. All these factors were measured by enzyme-linked immunosorbent assays. From the total of 60 cases, there was a significant increase (p<0.001) in PCOS patients when compared to the control group in fasting serum, serum interleukin-6 (IL-6), interleukin-8 (IL-8), resistin, leptin RBP-4, tumor necrosis factor-a (TNF-a) levels and insulin. A significant decrease in omentin-1 and ghrelin (p<0.001) was observed. The results also showed that 93.33% and 98.30% in PCOS patients had abnormal omentin1: Insulin ratio and omentin1: Resistin ratio respectively according to the cut off values ≤27.42 and ≤31.35. Moreover, 81.67% of PCOS patients had abnormal omentin1:IL-6 ratio according to the cut of value (≤66.09). This is the first time the role of plasma omentin1 has been investigated with respect to its implication in PCOS. Usually, LH/FSH ratio and FAI (ratio of total testosterone to SHBG) are the important factors used for the diagnosis of PCOS in all previous literature, but none of them referred to the parameters discussed in this report. Also, the percentage of sensitivity and the difference between range of these parameters in PCOS patients and the controls may give a different perspective in trying to understand the etiology of PCOS. Therefore, these parameters may be used for future diagnosis of PCOS. This study also suggested that omentin/resistin ratio may play a crucial paracrine or endocrine role in modulating insulin sensitivity.

Inhibitory effect of leptin on growth hormone secretion of GH3 cells: Involvement of cell proliferation, apoptosis and intracellular free Ca 2+

Recent studies have identified leptin and leptin receptors in the pituitary of different species, which suggest that there may be endocrine and paracrine regulatory roles between leptin-producing cells and cells with leptin receptor in pituitary, including growth and secretion of GH cells. The aim of this study was to investigate the effects of leptin on growth hormone (GH) secretion of GH3 cell. GH3 cells were cultured and treated with leptin. Cell proliferation was evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, distribution of cell cycle and rate of apoptosis determined by flow cytometry and fluorescence microscopy, and intracellular free Ca 2+ levels ([Ca 2+] i) of single GH3 cells measured by a laser scanning confocal microscope. Leptin (10 −9–10 −7 mol/L) at 1 day or longer of treatment inhibited the basal growth hormone secretion of GH3 cells ( P < 0.05), but had no significant effect on short-term treatment. Leptin inhibited cell proliferation, reduced the proportion of cells in DNA synthesis period (S phase) to inhibit DNA synthesis of GH3 cells, and accelerated cell apoptosis of GH3 cells. Furthermore, the level of [Ca 2+] i of single GH3 cell was found to decrease immediately upon the addition of leptin (10 −8 mol/L). Leptin inhibits the basal GH secretion of GH3 cells, which may be due to the inhibition of proliferation, DNA synthesis and advanced apoptosis of GH3 cell. The inhibition of leptin on GH synthesis and secretion may be related to intracellular free Ca 2+ level.

Menin regulates the function of hematopoietic stem cells and lymphoid progenitors

AbstractMen1 is a tumor suppressor gene mutated in endocrine neoplasms. Besides its endocrine role, the Men1 gene product menin interacts with the mixed lineage leukemia (MLL) protein, a histone H3 lysine 4 methyltransferase. Although menin and MLL fusion proteins cooperate to activate Homeobox (Hox) gene expression during transformation, little is known about the normal hematopoietic functions of menin. Here, we studied hematopoiesis after Men1 ablation. Menin loss modestly impaired blood neutrophil, lymphocyte, and platelet counts. Without hematopoietic stress, multilineage and myelo-erythroid bone marrow progenitor numbers were preserved, while B lymphoid progenitors were decreased. In contrast, competitive transplantation revealed a marked functional defect of long-term hematopoietic stem cells (HSC) in the absence of menin, despite normal initial homing of progenitors to the bone marrow. HoxA9 gene expression was only modestly decreased in menin-deficient HSCs. These observations reveal a novel and essential role for menin in HSC homeostasis that was most apparent during situations of hematopoietic recovery, suggesting that menin regulates molecular pathways that are essential during the adaptive HSC response to stress.

Menin regulates the function of hematopoietic stem cells and lymphoid progenitors

Men1 is a tumor suppressor gene mutated in endocrine neoplasms. Besides its endocrine role, the Men1 gene product menin interacts with the mixed lineage leukemia (MLL) protein, a histone H3 lysine 4 methyltransferase. Although menin and MLL fusion proteins cooperate to activate Homeobox (Hox) gene expression during transformation, little is known about the normal hematopoietic functions of menin. Here, we studied hematopoiesis after Men1 ablation. Menin loss modestly impaired blood neutrophil, lymphocyte, and platelet counts. Without hematopoietic stress, multilineage and myelo-erythroid bone marrow progenitor numbers were preserved, while B lymphoid progenitors were decreased. In contrast, competitive transplantation revealed a marked functional defect of long-term hematopoietic stem cells (HSC) in the absence of menin, despite normal initial homing of progenitors to the bone marrow. HoxA9 gene expression was only modestly decreased in menin-deficient HSCs. These observations reveal a novel and essential role for menin in HSC homeostasis that was most apparent during situations of hematopoietic recovery, suggesting that menin regulates molecular pathways that are essential during the adaptive HSC response to stress.

Adipocytes differentiation in the presence of Pluronic F127–coated carbon nanotubes

Carbon nanotubes are considered important nanodevices in biomedicine, and several applications in drug and gene delivery in different organs and tissues are presently under investigation. Among them very little attention has been dedicated to white adipose tissue (WAT), despite its wide distribution and endocrine role, which could potentially be used to release therapeutic agents. An important premise to use nanotubes in WAT is to determine their potential for toxicity on adipocytes. Here we show that Pluronic F127 (PF127)–coated multiwalled carbon nanotubes (MWCNTs) can be tolerated by NIH-3T3-L1 pre-adipocytes without affecting their growth. Moreover, the differentiation process of NIH-3T3-L1 pre-adipocytes to adipocytes is not compromised by the presence of 5 μg/mL MWCNTs in the medium. These results suggest that reasonable concentrations of PF127-MWCNTs are not toxic for adipocytes and do not interfere with their differentiation process. From the Clinical Editor This study established that Pluronic F127 (PF127)–coated multiwalled carbon nanotubes (MWCNTs) are tolerated by NIH-3T3-L1 pre-adipocytes. The differentation of these pre-adipocytes is not compromised by the presence of 5 μg/mL MWCNTs, suggesting that these nanotubes are not toxic for adipocytes.

IGF-IR/ERK content and response to IGF-I and insulin in adipocytes from small for gestational age children

Background/Aims The GH-IGF-I axis plays an important role on pre/postnatal growth in humans, and IGF-I regulates cell proliferation, differentiation, and metabolic homeostasis. The adipose tissue has an important function in energy storage, and plays an endocrine role through the production of several hormones and growth factors. There are few studies in humans regarding IGF-I and Insulin receptor signaling in adipocytes, particularly from AGA and SGA children. Methods We studied 22 healthy prepubertal children (6.1 ± 0.4 years), born at term (11 SGA and 11 AGA), and normal BMI at the time of the study. Primary cell cultures were established from subcutaneous adipose tissue biopsies. Preadipocytes were differentiated and stimulated with IGF-I or insulin and we studied IGF-IR, IR, AKT, and ERK content and phosphorylation. Results The SGA children were shorter than the AGA children (height SDS −2.14 ± 0.11 vs. 0.02 ± 0.19, p < 0.05). A lower content of IGF-IR, IR, AKT, and ERK was observed in adipocytes from SGA compared with AGA children. IGF-I stimulation increased IGF-IR and ERK phosphorylation in adipocytes from AGA, but not from SGA children. Conclusion The lower content and reduced phosphorylation of IGF-I signaling observed in adipocytes from SGA children may be related to the metabolic abnormalities described in these children.

Insulin/IGF-like signalling, the central nervous system and aging

Enormous strides in understanding aging have come from the discovery that mutations in single genes can extend healthy life-span in laboratory model organisms such as the yeast Saccharomyces, the fruit fly Drosophila melanogaster, the nematode worm Caenorhabditis elegans and the mouse. IIS [insulin/IGF (insulin-like growth factor)-like signalling] stands out as an important, evolutionarily conserved pathway involved in the determination of lifespan. The pathway has diverse functions in multicellular organisms, and mutations in IIS can affect growth, development, metabolic homoeostasis, fecundity and stress resistance, as well as lifespan. The pleiotropic nature of the pathway and the often negative effects of its disruption mean that the extent, tissue and timing of IIS manipulations are determinants of a positive effect on lifespan. One tissue of particular importance for lifespan extension in diverse organisms is the CNS (central nervous system). Although lowered IIS in the CNS can extend lifespan, IIS is also widely recognized as being neuroprotective and important for growth and survival of neurons. In the present review, we discuss our current understanding of the role of the nervous system in extension of lifespan by altered IIS, and the role of IIS in determination of neuronal function during aging. The nervous system can play both endocrine and cell-autonomous roles in extension of lifespan by IIS, and the effects of IIS on lifespan and neuronal function can be uncoupled to some extent. Tissue-specific manipulation of IIS and the cellular defence mechanisms that it regulates will better define the ways in which IIS affects neuronal and whole-organism function during aging.

Brain natriuretic peptide: Diagnostic potential in dogs

The endocrine role of the heart is evident in the secretion of noradrenaline and natriuretic peptides. The secretion of natriuretic peptides presents a useful mechanism for different conditions of cardiac dysfunction. Brain natriuretic peptide (BNP) has been accepted in human cardiology as a biomarker for cardiac insufficiency and coronary arterial disease. The specificity of the BNP structure is specie-specific, so that the testing of diagnostic and prognostic potential in dogs requires the existence of a test that is a homologue for that animal specie. The existence of an adequate method for measuring BNP concentration makes possible its implementation as a screening test in everyday clinical practice. .

The hormonal action of IGF1 in postnatal mouse growth

The mammalian insulin-like growth factor 1 (IGF1), which is a member of a major growth-promoting signaling system, is produced by many tissues and functions throughout embryonic and postnatal development in an autocrine/paracrine fashion. In addition to this local action, IGF1 secreted by the liver and circulating in the plasma presumably acts systemically as a classical hormone. However, an endocrine role of IGF1 in growth control was disputed on the basis of the results of a conditional, liver-specific Igf1 gene knockout in mice, which reduced significantly the level of serum IGF1, but did not affect average body weight. Because alternate interpretations of these negative data were tenable, we addressed genetically the question of hormonal IGF1 action by using a positive experimental strategy based on the features of the cre/loxP recombination system. Thus, we generated bitransgenic mice carrying in an Igf1 null background a dormant Igf1 cDNA placed downstream of a transcriptional "stop" DNA sequence flanked by loxP sites (floxed) and also a cre transgene driven by a liver-specific promoter. The Igf1 cDNA, which was inserted by knock-in into the mutated and inactive Igf1 locus itself to ensure proper transcriptional regulation, was conditionally expressed from cognate promoters exclusively in the liver after Cre-mediated excision of the floxed block. Our genetic study demonstrated that the endocrine IGF1 plays a very significant role in mouse growth, as its action contributes approximately30% of the adult body size and sustains postnatal development, including the reproductive functions of both mouse sexes.