THE JOURNAL OF SEXUAL MEDICINE, Issue 4 2005
Ahmed I. El-Sakka MD
ABSTRACT Introduction., Many patients with endocrinal changes (endocrinopathy) have some degrees of sexual dysfunction that necessitate assessment and treatment. Aim., To assess the prevalence, and identify the pattern, of endocrinopathy in patients with sexual dysfunction in our community. Methods., A total of 1,248 male patients with sexual dysfunction were enrolled in this study. Patients were screened for erectile dysfunction (ED) and sexual desire by the erectile function and the sexual desire domains of the International Index of Erectile Function (IEEF). Patients underwent routine laboratory investigations as well as total testosterone and prolactin assessment. All patients were referred to an endocrinologist for clinical and biochemical assessment of their endocrine function. The evaluation consisted of comprehensive history taking, physical examination, and, as needed, laboratory investigations. Results., Mean ages ± SD were 51.9 ± 12.2 and 52.3 ± 11.7 years for patients with and without endocrinopathy, respectively. Of the study population, 23.8% had endocrinopathy. The most frequent endocrinal changes were low testosterone level (15%), hyperprolactinemia (13.7%), and hypothyroidism (3.1%). There were significant associations between endocrinopathy and obesity, smoking, low desire, and premature ejaculation (P < 0.05 for each). Also, significant associations were found between low desire and low testosterone level, hyperprolactinemia, and hypothyroidism (P < 0.05 for each). Hyperprolactinemia was significantly associated with premature ejaculation (P < 0.05) but not with low testosterone level (P > 0.05). There was no significant association between endocrinopathy and age, cigarette smoking (number and duration), and ED (duration, severity, type of onset, and progression) (P > 0.05 for each). Conclusion., Endocrinopathy is not a rare condition among ambulatory patients with sexual dysfunction. This study provides a quantitative estimate of endocrinopathy in ambulatory patients with sexual dysfunction. [source]

Attack and defence in the gastric epithelium , a delicate balance

EXPERIMENTAL PHYSIOLOGY, Issue 4 2007
Rod Dimaline
The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin. [source]

Repressive Coping and Blood Measures of Disease Risk: Lipids and Endocrine and Immunological Responses to a Laboratory Stressor,

JOURNAL OF APPLIED SOCIAL PSYCHOLOGY, Issue 8 2000
Steven D. Barger
Relations between repressive coping and a variety of health-related variahles including insulin, lipids, catecholamines, and cellular immune components, were investigated in a laboratory study of acute stress among a sample of healthy male college students (N - 83). Compared to nonrepressors, at baseline, repressors had fewer numbers of circulating CD4 (T-helper) cells, greater numbers of natural killer (NK) cells. lower high-density lipoprotein (HDL), a higher total/HDL cholesterol ratio, and higher fasting insulin levels. In response to an acute laboratory stressor (Stroop Color Word Conflict Test). repressors demonstrated an attenuated increase in the number of circulating NK cells compared to nonrepressors. Confounds such as physical activity, age, and smoking were unrelated to the dependent measures. [source]

Octopus Gonadotrophin-Releasing Hormone: A Multifunctional Peptide in the Endocrine and Nervous Systems of the Cephalopod

JOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2009
H. Minakata
The optic gland, which is analogous to the anterior pituitary in the context of gonadal maturation, is found on the upper posterior edge of the optic tract of the octopus Octopus vulgaris. In mature octopus, the optic glands enlarge and secrete a gonadotrophic hormone. A peptide with structural features similar to that of vertebrate gonadotophin-releasing hormone (GnRH) was isolated from the brain of octopus and was named oct-GnRH. Oct-GnRH showed luteinising hormone-releasing activity in the anterior pituitary cells of the Japanese quail Coturnix coturnix. Oct-GnRH immunoreactive signals were observed in the glandular cells of the mature optic gland. Oct-GnRH stimulated the synthesis and release of sex steroids from the ovary and testis, and elicited contractions of the oviduct. Oct-GnRH receptor was expressed in the gonads and accessory organs, such as the oviduct and oviducal gland. These results suggest that oct-GnRH induces the gonadal maturation and oviposition by regulating sex steroidogenesis and a series of egg-laying behaviours via the oct-GnRH receptor. The distribution and expression of oct-GnRH in the central and peripheral nervous systems suggest that oct-GnRH acts as a multifunctional modulatory factor in feeding, memory processing, sensory, movement and autonomic functions. [source]

Capacity building through research and educational collaboration: a report of a UK,Sri Lanka collaboration

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2006
A Dissanayake MD Lecturer, International Training Fellow
Abstract Developing countries are faced with an escalating epidemic of non-communicable diseases. There is an urgent need to build capacity in terms of health care resources to combat this epidemic. In this article we describe a project co-funded by the World Diabetes Foundation, the Postgraduate Institute of Medicine Colombo Sri Lanka, the Endocrine and Metabolic Diseases Trust of Sri Lanka, and the charitable Sri Lanka Education Fund held in Trust at Sherwood Forest Hospitals NHS Trust, UK. This project has sought to improve capacity in a developing country through fostering research and educational partnerships. Copyright © 2006 John Wiley & Sons. [source]

Endocrine and Ovarian Responses to Prolonged Adrenal Stimulation at the Time of Induced Corpus Luteum Regression

REPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2006
G Gabai
Contents The endocrine and ovarian responses to prolonged adrenal stimulation at the time of corpus luteum (CL) regression were studied in non-lactating non-pregnant Friesian cows. Cows were synchronized with two cloprostenol (PG) injections 11 days apart (second PG referred as time 0). Experiment 1 was carried out on five animals in two phases with a resting period in between. Between ,48 and 84 h, animals received 12 injections of either saline (CTR) or adrenocorticotrophic hormone (ACTH) agonist (Synacthen; SYN) every 12 h. Cortisol (C), progesterone (P4), oestradiol (E2) and LH were analysed in the blood samples collected every 8,12 h between days ,3 and 4. Pulsatile LH release was studied 4 h before and 4 h after naloxone administration beginning at 96 h. Experiment 2 was carried out on four cows in a cross-over experimental design (two phases, with a resting period in between). Treatments were performed by administering either saline (CTR) or Synacthen (SYN) every 12 h between ,36 and 24 h. The concentrations of C, P4 and E2 were measured in blood plasma every 4,12 h from days ,3 to 3, then every day from days 5 to 9. In both experiments, ovaries were examined by ultrasonography every 1,3 days. ACTH administration induced a significant increase (p < 0.001) of plasma C lasting for 7 days (experiment 1), and for 3,4 days (experiment 2). Plasma C returned to baseline levels within 6 days (expt 1) or 36 h (expt 2) after treatment interruption. During the SYN phase, LH pre-ovulatory surge was not detectable. During the CTR phase, naloxone administration induced a significant increase (p < 0.05) of average LH concentrations that was not evident during the SYN phase. The dominant follicle development was retarded and mean plasma E2 concentrations were significantly lower during the SYN phase (p < 0.01). Luteolysis was completed within 2 days. However, P4 decline between 0 and 4 h was slower (p < 0.01) during the SYN phase. Our results indicate that, under prolonged adrenal stimulation, follicular development is delayed and LH release is impaired, which are independent of CL function. [source]

Endocrine and targeted manipulation of breast cancer: Proceedings of the Sixth Cambridge Conference April 30,May 1, 2007

CANCER, Issue S3 2008
Article first published online: 10 DEC 200
No abstract is available for this article. [source]

Transgenic mice for studies of the renin,angiotensin system in hypertension

ACTA PHYSIOLOGICA, Issue 4 2004
J. L. Lavoie
Abstract Hypertension is a polygenic and multi-factorial disorder that is extremely prevalent in western societies, and thus has received a great deal of attention by the research community. The renin,angiotensin system has a strong impact on the control of blood pressure both in the short- and long-term, making it one of the most extensively studied physiological systems. Nevertheless, despite decades of research, the specific mechanisms implicated in its action on blood pressure and electrolyte balance, as well as its integration with other cardiovascular pathways remains incomplete. The production of transgenic models either over-expressing or knocking-out specific components of the renin,angiotensin system has given us a better understanding of its role in the pathogenesis of hypertension. Moreover, our attention has recently been refocused on local tissue renin,angiotensin systems and their physiological effect on blood pressure and end-organ damage. Herein, we will review studies using genetic manipulation of animals to determine the role of the endocrine and tissue renin,angiotensin system in hypertension. We will also discuss some untraditional approaches to target the renin,angiotensin system in the kidney. [source]

Protein synthesis inhibition before or after stress exposure results in divergent endocrine and BDNF responses disassociated from behavioral responses

DEPRESSION AND ANXIETY, Issue 5 2008
Nitsan Kozlovsky Ph.D.
Abstract This study aimed to assess the effects of anisomycin, a protein synthesis inhibitor, on behavioral responses, brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels, and circulating corticosterone in rats,when administered before or after initial exposure to a predator scent stress stimulus. Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and exaggerated startle reaction as well as corticosterone levels and mRNA BDNF and TrkB were compared in rats exposed to predator stress, microinjected with anisomycin before or after stress exposure. Administration of anisomycin before or after stress exposure reduced anxiety-like behavior in the elevated plus-maze and reduced the mean startle amplitude 7 days postexposure. Although the behavioral responses were similar when anisomycin was microinjected before or after stress exposure, the levels of mRNAs for BDNF and TrkB, which play a role in modulation of synaptic plasticity and the consolidation process, showed varying responses. Depression and Anxiety 0:1,11, 2007. © 2007 Wiley-Liss, Inc. [source]

Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling

DEVELOPMENTAL DYNAMICS, Issue 4 2007
Mamdouh H. Kedees
Abstract Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase-2 (PC2,/,), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr,/,). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling. Developmental Dynamics 236:1126,1133, 2007. © 2007 Wiley-Liss, Inc. [source]

Analysis of pancreatic endocrine development in GDF11-deficient mice

DEVELOPMENTAL DYNAMICS, Issue 11 2006
Darwin S. Dichmann
Abstract Here, we examine the role of GDF11 in pancreatic development. Using in situ hybridization and reverse transcriptase-polymerase chain reaction analyses, we show that Gdf11 transcripts are expressed in embryonic pancreas epithelium before the secondary transition but decrease rapidly afterward. To determine the function of GDF11 during pancreas development, we analyzed Gdf11,/, mouse embryos. In such embryos, pancreas size is twofold reduced at embryonic day (E) 18 compared with wild-type littermates. Quantification of the different tissue compartments shows a specific hypoplasia of the exocrine compartment, while the endocrine and ductal compartments are unaffected. Notably, NGN3+ endocrine precursor cells are increased fourfold at E18, although the amount of endocrine cells in the pancreas of these animals is unchanged compared with wild-type littermates. Similarly, the maturation of endocrine cells as well as the ratio between ,- and ,-cells appears normal. Developmental Dynamics 235:3016,3025, 2006. © 2006 Wiley-Liss, Inc. [source]

Outcome of craniopharyngioma in children: long-term complications and quality of life

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2004
Andrea Poretti MB BS
Childhood craniopharyngiomas are histologically benign tumours arising from remnants of Rathke's pouch in the hypothalamic,pituitary region. The two common treatment approaches are primary total resection or limited resection followed by radiotherapy. To study the outcome after a primary surgical approach, we followed 25 consecutive patients (10 females, 15 males) under 16 years of age who were treated in a single institution with a management policy of radical tumour excision (mean age at diagnosis 9 years 2 months, SD 4 years 3 months; range 2 years 9 months to 15 years 11 months). Mean follow-up after primary surgery was 11 years 3 months (SD 7 years 7 months). Tumour control, and neurological, endocrine, and hypothalamic complications and their impact on health-related quality of life were assessed (medical follow-up, semi-structured interview, and questionnaires). Results of tumour control were generally good, however, local failure was observed in 6 of 25 patients, and severe late-treatment complications decreased quality of life for many long-time survivors. Endocrine deficiency occurred in 24/25, visual complications in 16/24, neurological complications in 8/24, obesity in 14/23, increased daytime sleepiness in 6/21, and significant school problems in 10/20. Patients with craniopharyngioma rated their health-related quality of life as considerably lower than healthy controls; the domains of social and emotional functioning were particularly affected. Parents'ratings were considerably lower than those of the patients. Poor functional outcome was associated with large tumours infiltrating or displacing the hypothalamus, the occurrence of hydrocephalus, and young age at diagnosis, but also with multiple operations due to tumour recurrence. Alternative treatment strategies should be considered, especially in very young patients with large tumours. [source]

Ontogeny of energy homeostatic pathways via neuroendocrine signaling in Atlantic salmon

DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2010
Anne-Grethe Gamst Moen
Abstract Leptin and ghrelin are known to regulate energy homeostasis via hypothalamic neuropeptide signaling in mammals. Recent studies have discovered that these hormones exist in teleosts, however, very little is known concerning their role during teleost ontogeny. Here, we have examined the steady state levels of leptins, ghrelins, their target neuropetides and several growth factors during Atlantic salmon development. Initial experiments revealed differential expression of leptin genes and ghrelin isoforms during embryogenesis. In larvae, equal upregulation of ghrl1 and ghrl2 was observed just prior to exogenous feeding while a surge of lepa1 occurred one week after first-feeding. Subsequent dissection of the embryos and larvae showed that lepa1, cart, pomca1, and agrp are supplied as maternal transcripts. The earliest zygotic expression was observed for lepa1 and cart at 320 day degrees. By 400 day degrees, this expression was localized to the head and coincided with upregulation of ghrl2 and npy. Over the hatching period growth factor signaling predominated. The ghrelin surge prior to first-feeding was exclusively localized in the internal organs and coincided with upregulation of npy and agrp in the head and agrp in the trunk. One week after exogenous feeding was established major peaks were detected in the head for lepa1 and pomca1 with increasing levels of cart, while lepa1 was also significantly expressed in the trunk. By integrating theses data into an ontogenetic model, we suggest that the mediation of Atlantic salmon energy homeostatic pathways via endocrine and neuropeptide signaling retains putative features of the mammalian system. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 649,658, 2010 [source]

Maternally separated rats show deficits in maternal care in adulthood

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2001
Vedran Lovic
Abstract Although there is considerable research on the phenomenology, neuroendocrinology, neuroanatomy, and sensory control of maternal behavior, little is known about the influences of early postnatal and postweaning experiences on the development of maternal behavior. The purpose of this study was to assess how early life separation from the mother rat affects development of the offspring's juvenile and adult maternal behavior. From postnatal Days 1 to 17, 3 female rats within each litter were separated (SEP) from the mother and the rest of the litter for 5 hr daily while 3 of their sisters were not maternally separated (NSEP). On postnatal Day 21, all subjects were weaned and randomly assigned to one of three juvenile conditions. One female from both SEP and NSEP groups was either isolated (I), given a social conspecific (S), or given 1- to 4-day-old pups (P) for 5 consecutive days. Maternal behavior of SEP and NSEP animals was assessed and recorded on each of the 5 days. Once all animals reached adulthood, they were mated, gave birth, and were assessed for their maternal behavior. We found that the effects of maternal separation on juvenile maternal-like behaviors were minimal. On the other hand, maternal separation reduced adult maternal licking and crouching over pups. In addition, there was a significant interaction between postnatal and juvenile experience on maternal crouching in maternal animals. These results are discussed in terms of the variety of possible behavioral, endocrine, and neurochemical mechanisms that mediate the effects of early life experiences on adult maternal behavior. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 19,33, 2001 [source]

VMAT2 quantitation by PET as a biomarker for ,-cell mass in health and disease

DIABETES OBESITY & METABOLISM, Issue 2008
M. Freeby
The common pathology underlying both type 1 and type 2 diabetes (T1DM and T2DM) is insufficient ,-cell mass (BCM) to meet metabolic demands. An important impediment to the more rapid evaluation of interventions for both T1DM and T2DM lack of biomarkers of pancreatic BCM. A reliable means of monitoring the mass and/or function of ,-cells would enable evaluation of the progression of diabetes as well as the monitoring of pharmacologic and other interventions. Recently, we identified a biomarker of BCM that is quantifiable by positron emission tomography (PET). PET is an imaging technique which allows for non-invasive measurements of radioligand uptake and clearance, is sensitive in the pico- to nanomolar range and of which the results can be deconvoluted into measurements of receptor concentration. For BCM estimates, we have identified VMAT2 (vesicular monoamine transporter type 2) as a biomarker and [11C] DTBZ (dihydrotetrabenazine) as the transporter's ligand. VMAT2 is highly expressed in ,-cells of the human pancreas relative to other cells of the endocrine and exocrine pancreas. Thus measurements of [11C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements [source]

Metabolic, endocrine and haemodynamic risk factors in the patient with peripheral arterial disease

DIABETES OBESITY & METABOLISM, Issue 2002
Jill J. F. Belch
The morbidity and mortality associated with peripheral arterial disease (PAD) creates a huge burden in terms of costs both to the patient and to the health service. PAD is a deleterious and progressive condition that causes a marked increase in the risk of cardiovascular and cerebrovascular events. Further, PAD has a major negative impact on quality of life and mortality, and is associated with an increased risk of limb amputation. The clinical profile of patients at risk of PAD overlaps considerably with the known cardiovascular risk factors. These include, increasing age, smoking habit, diabetes, hypertension, dyslipidaemia, male sex and hyperhomocysteinaemia. For women, hormone replacement therapy appears to be associated with a reduced risk of PAD. Published PAD guidelines recommend aggressive management of risk factors, stressing the importance of lifestyle modification, antiplatelet agents, treating dyslipidaemia and diabetes. However, a large number of patients with PAD go undetected, either because they do not report their symptoms or because they are asymptomatic. It is therefore important to improve detection rates so that these patients can receive appropriate risk factor management. [source]

The mode of action of thiazolidinediones,

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002
Hans Hauner
Abstract The thiazolidinediones (TZDs) or ,glitazones' are a new class of oral antidiabetic drugs that improve metabolic control in patients with type 2 diabetes through the improvement of insulin sensitivity. TZDs exert their antidiabetic effects through a mechanism that involves activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPAR,), a nuclear receptor. TZD-induced activation of PPAR, alters the transcription of several genes involved in glucose and lipid metabolism and energy balance, including those that code for lipoprotein lipase, fatty acid transporter protein, adipocyte fatty acid binding protein, fatty acyl-CoA synthase, malic enzyme, glucokinase and the GLUT4 glucose transporter. TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR, is predominantly expressed in adipose tissue. It is possible that the effect of TZDs on insulin resistance in muscle and liver is promoted via endocrine signalling from adipocytes. Potential signalling factors include free fatty acids (FFA) (well-known mediators of insulin resistance linked to obesity) or adipocyte-derived tumour necrosis factor-, (TNF-,), which is overexpressed in obesity and insulin resistance. Although there are still many unknowns about the mechanism of action of TZDs in type 2 diabetes, it is clear that these agents have the potential to benefit the full ,insulin resistance syndrome' associated with the disease. Therefore, TZDs may also have potential benefits on the secondary complications of type 2 diabetes, such as cardiovascular disease. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South Africa

ENVIRONMENTAL TOXICOLOGY, Issue 2 2009
M. J. Marchand
Abstract There is a need for sensitive bio-monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long-term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology-based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source]

Evaluation of the methoxytriazine herbicide prometon using a short-term fathead minnow reproduction test and a suite of in vitro bioassays

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2006
Daniel L. Villeneuve
Abstract Prometon is one of the most consistently detected herbicides in the U.S. environment. However, no previous assessment of the potential for prometon or related methoxytriazine herbicides to act as endocrine-disrupting chemicals has been conducted. This study used an array of in vitro bioassays to assess whether prometon, atraton, terbumeton, or secbumeton might act as potent (ant)agonists of the aryl hydrocarbon, estrogen, androgen, or glucocorticoid receptors or as aromatase inhibitors or inducers in vitro. Potential effects of prometon were also evaluated using a 21-d fathead minnow reproduction assay. Concentrations of methoxytriazines, as great as 1 mg/L (4.4 ,M), did not induce significant dioxin-like responses in H4IIE-luc cells, estrogenic responses in MVLN cells, or androgen or glucocorticoid receptor,mediated responses in MDA-kb2 cells, nor did the methoxytriazines significantly affect aromatase activity in vitro. In the fathead minnow assay, exposure to 20, 200, or 1,000 ,g prometon/L significantly reduced the weight of the male fat pad (an androgen-responsive tissue) relative to body weight. Exposure to 20 ,g prometon/L significantly increased female plasma testosterone concentrations, but the effect was not observed at greater concentrations. Overall, prometon did not significantly reduce fecundity over the 21-d exposure, nor were other endpoints, including plasma vitellogenin and estradiol concentrations, brain and ovary aromatase activity, and male tubercle index, significantly affected. Evidence from our work suggests that prometon may cause subtle endocrine and/or reproductive effects in fathead minnows, but no clear mechanism of action was observed. The relevance of these effects to hazard assessment for the pesticide is uncertain. [source]

Metabolic age modelling: the lesson from centenarians

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2000
G. Paolisso
Evolutionary theories of ageing, and data emerging from cellular and molecular biology of ageing, suggested that animals and humans capable of reaching an age close to the extreme limit of the life span should be equipped with a very efficient network of anti-ageing mechanisms. Indeed several evidences have demonstrated that starting from young to very old subjects, ageing is associated with a progressive remodelling. Thus, a new paradigm, the remodelling theory of age, was proposed. This theory, focusing on the human immune system, suggested that immunosenescence is the net result of the continuous adaptation of the body to the deteriorative changes occurring over time. According to this hypothesis, body resources are continuously optimized, and immunosenescence must be considered a very dynamic process including both loss and gain. Whether the metabolic pathways and the endocrine functions are also part of the age remodelling is not investigated. The aim of this review is to focus on the age-related changes in metabolic pathways and endocrine functions and to demonstrate that healthy centenarians (HC) represent the best living example of successful age-remodelling in whom the age remodelling has occurred without problems. In order to design the clinical picture of such successful ageing, anthropometric, endocrine and metabolic characteristics of healthy centenarians (HC), compared with aged subject, have been outlined. [source]

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2010
D. Pavlovic
Objective:, The objective of the study was to asses the possible influence of hypothalamo,pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. Design:, We performed retrospective and cross-sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 ± 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 ± 0.6 years). Serum insulin-like growth factor 1 (IGF-I), thyroxin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide-6 (GHRP-6) test. Cognitive function was assessed by using a standard neuropsychological battery. Results:, GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF-I level. Conclusions:, GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI. [source]

Myotonic dystrophy type 2

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2002
J. Finsterer
Myotonic dystrophy type 2 (DM2) is a clinically but not genetically heterogeneous, multisystem disorder, that is clinically similar to, but distinct from myotonic dystrophy type 1 (DM1). Initially, different phenotypes of DM2 were described by Ricker (proximal myotonic myopathy, PROMM), Ranum (myotonic dystrophy 2, DM2) and Udd (proximal myotonic dystrophy, PDM). Clinical features these three phenotypes had in common were diffuse, proximal or distal weakness, wasting, myotonia, cataract, cerebral, endocrine and cardiac abnormalities. Initially, the clinical differences between DM1 and PROMM seemed unmistakable, but meanwhile it has become apparent that the clinical differences between these entities are blurring. In 1999, Day et al., Meola et al. and Ricker et al. mapped the mutated gene of all three phenotypes to chromosome 3q. In 2001, the three different phenotypes were found to rely on the same mutation in the ZNF9 gene on chromosome 3q21.3. Although DM2 may be clinically heterogeneous, it is by result of a mutation in a single gene. The mutation responsible for DM2 is a CCTG-repeat expansion of 75,11 000 repeats in intron 1 of the ZNF9 gene on chromosome 3q21.3. Because of the clinical heterogeneity, the diagnosis of DM2 should rely on DNA analysis alone. [source]

Differential routing of coexisting neuropeptides in vasopressin neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003
Marc Landry
Abstract The functional implications of intraneuronal coexistence of different neuropeptides depend on their respective targeting to release sites. In the rat hypothalamic magnocellular neurons, we investigated a possible differential routing of the coexpressed galanin and vasopressin. The respective location of proteins and messengers was assessed with double immunogold and in situ hybridization combining confocal and electron microscope analysis. The various populations of labelled granules were quantitatively compared in three subcellular compartments: perikarya, local processes and posthypophyseal nerve endings. Three subpopulations of granules were detected in all three compartments, but their respective amount showed significant differences. Galanin alone was immunolocalized in some secretory granules, vasopressin alone in others, and both peptides in a third subpopulation of granules. The major part of the granules containing vasopressin, either alone or in association with galanin, is found in neurohypophyseal nerve endings. In contrast, galanin single-labelled granules represent the most abundant population in dendritic processes, while double-labelled granules are more numerous in perikarya. This indicates a preferential distribution of the two peptides in the different compartments of magnocellular neurons. Furthermore, galanin and vasopressin messenger RNAs were detected at different domains of the endoplasmic reticulum, suggesting that translation might also occur at different locations, thus leading to partial segregation of galanin and vasopressin cargoes between two populations of secretory granules. The present study provides, for the first time in mammals, evidence suggesting that galanin and vasopressin are only partly copackaged and undergo a preferential targeting toward dendrites or neurohypophysis, suggesting different functions, autocrine/paracrine and endocrine, respectively. [source]

Differential routing of coexisting neuropeptides in vasopressin neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003
Marc Landry
Abstract The functional implications of intraneuronal coexistence of different neuropeptides depend on their respective targeting to release sites. In the rat hypothalamic magnocellular neurons, we investigated a possible differential routing of the coexpressed galanin and vasopressin. The respective location of proteins and messengers was assessed with double immunogold and in situ hybridization combining confocal and electron microscope analysis. The various populations of labelled granules were quantitatively compared in three subcellular compartments: perikarya, local processes and posthypophyseal nerve endings. Three subpopulations of granules were detected in all three compartments, but their respective amount showed significant differences. Galanin alone was immunolocalized in some secretory granules, vasopressin alone in others, and both peptides in a third subpopulation of granules. The major part of the granules containing vasopressin, either alone or in association with galanin, is found in neurohypophyseal nerve endings. In contrast, galanin single-labelled granules represent the most abundant population in dendritic processes, while double-labelled granules are more numerous in perikarya. This indicates a preferential distribution of the two peptides in the different compartments of magnocellular neurons. Furthermore, galanin and vasopressin messenger RNAs were detected at different domains of the endoplasmic reticulum, suggesting that translation might also occur at different locations, thus leading to partial segregation of galanin and vasopressin cargoes between two populations of secretory granules. The present study provides, for the first time in mammals, evidence suggesting that galanin and vasopressin are only partly copackaged and undergo a preferential targeting toward dendrites or neurohypophysis, suggesting different functions, autocrine/paracrine and endocrine, respectively. [source]

New genomic avenues in behavioural neuroendocrinology ,

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2002
S. L. Lightman
Abstract Neuroendocrine systems play a key role not only in the maintenance of whole-body homeostasis but also as the link between behavioural, endocrine and autonomic responses to environmental stimuli. It is becoming increasingly clear that neuroendocrine regulatory mechanisms are under the control of a combination of factors including genetic background, environment and early-life programming. Patterns of gene expression are increasingly being used to provide information on the genotypes associated with particular behaviours, and modulation of specific parts of the genome allow investigation of the contribution of particular genes. The sequencing of the genome provides a unique opportunity to elucidate the genetic contribution to neuroendocrine and behavioural processes, and to investigate the interactions between genetic and environmental factors. Although drugs can be used to activate or inhibit neurotransmitters and receptors, they lack specificity. New technologies now permit the activation or inactivation of both neurotransmitters and receptors in specific areas of the brain for defined periods, including crucially important developmental windows when activation appears to have long-term consequences. The future challenges are to define the critical mechanisms through which the genetic constitution of an individual human or experimental animal interacts with environmental cues to result in altered physiological or even pathological behaviour and endocrine function. [source]

Physiological Society Symposium , the Athlete's Heart

EXPERIMENTAL PHYSIOLOGY, Issue 5 2003
Athlete's heart, effect of age, ethnicity, sporting discipline
Regular physical training is associated with several physiological and biochemical adaptations which enable an increase in cardiac output and widening of the systemic arterio-venous oxygen difference. An increase in cardiac chamber size is fundamental to the generation of a sustained increase in cardiac output for prolonged periods. Echocardiographic studies have shown that the vast majority of athletes have modest cardiac enlargement although a small proportion exhibit substantial increases in heart size. Recognised determinants of cardiac size include age, sex, ethnicity and type of sport. Cardiac dimensions vary considerably amongst athletes, even when allowances are made for these variables, suggesting that genetic, endocrine and biochemical factors also influence heart size. This review discusses the effects of age, sex, ethnicity and sporting discipline on cardiac dimensions in athletic individuals. [source]

The C-terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitro

FEBS JOURNAL, Issue 13 2007
Nadia Rabah
The proprotein convertase PC1/3 preferentially cleaves its substrates in the dense core secretory granules of endocrine and neuroendocrine cells. Similar to most proteinases synthesized first as zymogens, PC1/3 is synthesized as a larger precursor that undergoes proteolytic processing of its signal peptide and propeptide. The N-terminally located propeptide has been shown to be essential for folding and self-inhibition. Furthermore, PC1/3 also possesses a C-terminal region (CT-peptide) which, for maximal enzymatic activity, must also be cleaved. To date, its role has been documented through transfection studies in terms of sorting and targeting of PC1/3 and chimeric proteins into secretory granules. In this study, we examined the properties of a 135-residue purified bacterially produced CT-peptide on the in vitro enzymatic activity of PC1/3. Depending on the amount of CT-peptide used, it is shown that the CT-peptide increases PC1/3 activity at low concentrations (nm) and decreases it at high concentrations (µm), a feature typical of an activator. Furthermore, we show that, contrary to the propeptide, the CT-peptide is not further cleaved by PC1/3 although it is sensitive to human furin activity. Based on these results, it is proposed that PC1/3, through its various domains, is capable of controlling its enzymatic activity in all regions of the cell that it encounters. This mode of self-control is unique among members of all proteinases families. [source]

Characterization of natural vasostatin-containing peptides in rat heart

FEBS JOURNAL, Issue 14 2006
Elise Glattard
Chromogranin A (CGA) is a protein that is stored and released together with neurotransmitters and hormones in the nervous, endocrine and diffuse neuroendocrine systems. As human vasostatins I and II [CGA(1,76) and CGA(1,113), respectively] have been reported to affect vessel motility and exert concentration-dependent cardiosuppressive effects on isolated whole heart preparations of eel, frog and rat (i.e. negative inotropism and antiadrenergic activity), we investigated the presence of vasostatin-containing peptides in rat heart. Rat heart extracts were purified by RP-HPLC, and the resulting fractions analyzed for the presence of CGA N-terminal fragments using dot-blot analysis. CGA-immunoreactive fractions were submitted to western blot and MS analysis using the TOF/TOF technique. Four endogenous N-terminal CGA-derived peptides [CGA(4,113), CGA(1,124), CGA(1,135) and CGA(1,199)] containing the vasostatin sequence were characterized. The following post-translational modifications of these fragments were identified: phosphorylation at Ser96, O-glycosylation (trisaccharide, NAcGal-Gal-NeuAc) at Thr126, and oxidation at three methionine residues. This first identification of CGA-derived peptides containing the vasostatin motif in rat heart supports their role in cardiac physiology by an autocrine/paracrine mechanism. [source]

Psychiatric endophenotypes and the development of valid animal models

GENES, BRAIN AND BEHAVIOR, Issue 2 2006
T. D. Gould
Endophenotypes are quantifiable components in the genes-to-behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other. [source]

Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice

GENES, BRAIN AND BEHAVIOR, Issue 2 2003
O. Stork
We investigated the involvement of the 65 kDa isoform of glutamic acid decarboxylase (GAD65) and GAD65-mediated ,-aminobutyric acid (GABA) synthesis in the formation and expression of Pavlovian fear memory. To this end, behavioral, endocrine and autonomic parameters were examined during conditioned fear retrieval of mice with targeted ablation of the GAD65 gene (GAD65,/, mice). These mutant mice were found to display specific fear behavior (freezing, escape), as well as autonomic (increased defecation) and endocrine activation (increased plasma corticosterone) during fear memory retrieval. However, freezing was reduced and flight and escape behavior were increased in GAD65,/, mice compared to their wild type and heterozygous littermates, while corticosterone levels and defecation rates did not differ between genotypes. Active defensive behavior of GAD65,/, mice was observed during both auditory cued and contextual retrieval of fear memory, as well as immediately after conditioning. These data indicate a selectively altered behavioral fear response in GAD65,/, mice, most likely due to deficits in threat estimation or the elicitation of appropriate conditioned fear behavior, and suggest that GAD65 is a genetic determinant of conditioned fear behavior. GAD65,/, mice provide a valuable tool to further dissect the GABAergic mechanisms involved in fear and anxiety and to model GABA-related neurological and psychiatric disorders. [source]