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1.
Mil Med ; 184(5-6): e298-e302, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30371879

RESUMO

INTRODUCTION: Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model. MATERIALS AND METHODS: Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death. RESULTS: Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups. CONCLUSIONS: Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.


Assuntos
Aorta/cirurgia , Oclusão com Balão/efeitos adversos , Sistema Endócrino/enzimologia , Aldosterona/análise , Aldosterona/sangue , Angiotensina II/análise , Angiotensina II/sangue , Animais , Aorta/enzimologia , Oclusão com Balão/métodos , Modelos Animais de Doenças , Sistema Endócrino/irrigação sanguínea , Hidrocortisona/análise , Hidrocortisona/sangue , Renina/análise , Renina/sangue , Estatísticas não Paramétricas , Suínos
2.
Artigo em Inglês | MEDLINE | ID: mdl-26439857

RESUMO

We hypothesize that glucosensor mechanisms other than that mediated by glucokinase (GK) are present in the liver and Brockmann bodies (BB) of rainbow trout, and are affected by stress. We evaluated in these tissues changes in parameters related to putative glucosensor mechanisms based on liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and SGLT-1 6h after intraperitoneal injection of saline solution alone (normoglycaemic treatment) or containing insulin (hypoglycaemic treatment), or d-glucose (hyperglycaemic treatment). Half of tanks were kept at normal stocking density (NSD; 10kgfishmass·m(-3)) whereas the remaining tanks were kept at high stocking density (HSD; 70kgfishmass·m(-3)). The results provide for the first time in fish evidence for the presence of putative glucosensor systems based on mitochondrial activity and sweet taste receptor in liver whereas in BB systems based on LXR, mitochondrial activity, sweet taste receptor, and SGLT-1 could be operative. We also obtained for the first time in fish evidence for the functioning of integrative metabolic sensors in response to changes in nutrient levels since changes in the mRNA abundance of sirtuin 1 (SIRT-1) were observed in response to increased glucose levels. The stress conditions elicited by HSD altered the response of the glucosensor systems based on mitochondrial activity, sweet taste receptor, and SGLT-1 in the liver, and LXR and SGLT-1 in the BB.


Assuntos
Sistema Endócrino/metabolismo , Glucoquinase/metabolismo , Glucose/metabolismo , Fígado/metabolismo , Animais , Sistema Endócrino/enzimologia , Regulação Enzimológica da Expressão Gênica , Fígado/enzimologia , Oncorhynchus mykiss/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Mol Cell Endocrinol ; 366(2): 170-9, 2013 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-22801104

RESUMO

AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis involved in the regulation of a number of physiological processes including ß-oxidation of fatty acids, lipogenesis, protein and cholesterol synthesis, as well as cell cycle inhibition and apoptosis. Important changes to these processes are known to occur in cancer due to changes in AMPK activity within cancer cells and in the periphery. This review aims to present findings relating to the role and regulation of AMPK in endocrine-related cancers. Obesity is a known risk factor for many types of cancers and a number of endocrine factors, including adipokines and steroid hormones, are regulated by and regulate AMPK. A clear role for AMPK in breast cancer is evident from the already impressive body of work published to date. However, information pertaining to its role in prostate cancer is still contentious, and future work should unravel the intricacies behind its role to inhibit, in some cases, and stimulate cancer growth in others. This review also presents data relating to the role of AMPK in cancers of the endometrium, ovary and colon, and discusses the possible use of AMPK-activating drugs including metformin for the treatment of all endocrine-related cancers.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias do Colo/enzimologia , Neoplasias do Endométrio/enzimologia , Obesidade/enzimologia , Neoplasias Ovarianas/enzimologia , Neoplasias da Próstata/enzimologia , Proteínas Quinases Ativadas por AMP/genética , Fatores Biológicos/farmacologia , Transformação Celular Neoplásica , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/enzimologia , Sistema Endócrino/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Obesidade/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética
4.
Endocr Rev ; 33(2): 216-53, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22402194

RESUMO

Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors.


Assuntos
Carboxipeptidase H/fisiologia , Sistema Nervoso Central/enzimologia , Sistema Endócrino/enzimologia , Neoplasias/enzimologia , Animais , Humanos , Modelos Animais
5.
Eur J Endocrinol ; 165(2): 177-88, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21602319

RESUMO

The cAMP-protein kinase A pathway plays a central role in the development and physiology of endocrine tissues. cAMP mediates the intracellular effects of numerous peptide hormones. Various cellular and molecular alterations of the cAMP-signaling pathway have been observed in endocrine diseases. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. Indeed, PDEs are the only known mechanism for inactivation of cAMP by catalysis to 5'-AMP. It has been suggested that disruption of PDEs could also have a role in the pathogenesis of many endocrine diseases. This review summarizes the most recent advances concerning the role of the PDEs in the physiopathology of endocrine diseases. The potential significance of this knowledge can be easily envisaged by the development of drugs targeting specific PDEs.


Assuntos
Doenças do Sistema Endócrino/etiologia , Sistema Endócrino/fisiologia , Diester Fosfórico Hidrolases/fisiologia , Animais , Sistema Endócrino/enzimologia , Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/genética , Doenças do Sistema Endócrino/metabolismo , Humanos , Modelos Biológicos , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo
6.
Nat Rev Endocrinol ; 7(7): 420-30, 2011 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-21448143

RESUMO

Telomeres are nucleoprotein complexes located at the ends of chromosomes that have a critical role in the maintenance of chromosomal integrity. This involvement is based on complex secondary and tertiary structures that rely on DNA-DNA, DNA-protein and protein-protein interactions. De novo synthesis and maintenance of telomere repeats is controlled by telomerase, a specialized complex that consists of a telomerase RNA component and a protein component--telomerase reverse transcriptase. When telomerase is silent (its default state in differentiated somatic cells), chromosomes shorten with every cell division, thus limiting the lifespan of the cells (the process of senescence) and preventing unlimited cell proliferation, which might eventually lead to the development of cancer. During this process, occasionally, a cell can activate telomerase, which stabilizes short telomeres and enables immortalization-a process essential for malignant transformation. Thus, although telomere erosion is a barrier to malignant progression, paradoxically, in certain circumstances it might also trigger tumorigenesis. A number of studies have demonstrated unequivocally that reactivation of telomerase in the presence of short telomeres is one of the most common features of human cancers, including those of the endocrine system.


Assuntos
Proteínas Cromossômicas não Histona/química , Sistema Endócrino/enzimologia , Neoplasias/enzimologia , Telomerase/metabolismo , Telômero/metabolismo , Animais , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Expansão das Repetições de DNA , Humanos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/etiologia , Neoplasias/genética , RNA/química , RNA/genética , RNA/metabolismo , Telomerase/química , Telomerase/genética , Telômero/química , Telômero/genética
8.
J Mol Endocrinol ; 45(4): 183-91, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20660167

RESUMO

Ectoenzymes are a family of cell surface molecules whose catalytic domain lies in the extracellular region. A subset of this family, nucleotide-metabolizing ectoenzymes, are key components in the regulation of the extracellular balance between nucleotides (e.g. NAD(+) or ATP) and nucleosides (e.g. adenosine). Their substrates and products are signalling molecules that act by binding to specific receptors, triggering signals that regulate a variety of functions, ranging from the migration of immune cells, to synaptic transmission in the brain, to hormone/receptor interactions in the glands. Almost two decades of accumulated data indicate that these regulatory processes significantly affect the endocrine system, a tightly controlled information signal complex with clear evidence of fine regulation. Functional models discussed in this review include insulin secretion, bone modelling and the association between hormones and behaviour. The emerging pattern is one of a system operating as a scale-free network that hinges around hubs of key molecules, such as NAD(+) or ATP. The underlying natural link between nucleotides, ectoenzymes and the endocrine system is far from being clearly demonstrated. However, the body of evidence supporting the existence of such connection is growing exponentially. This review will try to read the available evidence in a hypothesis-oriented perspective, starting from the description of NAD(+) and of ecto- and endoenzymes involved in its metabolism.


Assuntos
Sistema Endócrino/enzimologia , Enzimas/metabolismo , NAD/metabolismo , Animais , Humanos , Modelos Biológicos
9.
J Appl Physiol (1985) ; 107(4): 1006-14, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19696361

RESUMO

Skeletal muscle is an endocrine organ that produces and releases myokines in response to contraction. Some myokines are likely to work in a hormone-like fashion, exerting specific endocrine effects on other organs such as the liver, the brain, and the fat. Other myokines will work locally via paracrine mechanisms, exerting, e.g., angiogenetic effects, whereas yet other myokines work via autocrine mechanisms and influence signaling pathways involved in fat oxidation and glucose uptake. The finding that muscles produce and release myokines creates a paradigm shift and opens new scientific, technological, and scholarly horizons. This finding represents a breakthrough within integrative physiology and contributes to our understanding of why regular exercise protects against a wide range of chronic diseases. Thus the myokine field provides a conceptual basis for the molecular mechanisms underlying, e.g., muscle-fat, muscle-liver, muscle-pancreas, and muscle-brain cross talk.


Assuntos
Sistema Endócrino/metabolismo , Interleucina-6/metabolismo , Contração Muscular , Músculo Esquelético/metabolismo , Transdução de Sinais , Tecido Adiposo/metabolismo , Animais , Comunicação Autócrina , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sistema Endócrino/enzimologia , Exercício Físico , Humanos , Interleucina-15/metabolismo , Interleucina-8/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/enzimologia , Neovascularização Fisiológica , Comunicação Parácrina
10.
J Comp Physiol B ; 178(6): 655-72, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18404270

RESUMO

Food protein hydrolysis, a crucial step in digestion, is catalyzed by trypsin enzymes from the digestive apparatus of invertebrates. Trypsin appeared early in evolution and occurs in all phyla and, in the digestive systems of invertebrates, it became the most abundant proteinase. As in vertebrates, invertebrate trypsin is also present in several forms (isoenzymes). Its physiological importance in food protein digestion in several invertebrate species has emerged with compelling evidence; and several other physiological functions, such as regulation of digestive functions, are now settled. Recent advances in the knowledge of invertebrate trypsin synthesis, regulation, genetics, catalytic characteristics; structure, evolution, as well as inhibition, especially in non-Drosophilidae insects and in some crustaceans are reviewed. Most of the existing information is largely based on the use of several tools, including molecular techniques, to answer many still open questions and solve medical, agricultural, and food quality problems.


Assuntos
Proteínas na Dieta/metabolismo , Sistema Digestório/enzimologia , Invertebrados/enzimologia , Tripsina/metabolismo , Tripsinogênio/metabolismo , Adaptação Fisiológica , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Crustáceos/enzimologia , Sistema Endócrino/enzimologia , Ativação Enzimática , Evolução Molecular , Regulação Enzimológica da Expressão Gênica , Hidrólise , Hormônios de Inseto/metabolismo , Proteínas de Insetos/metabolismo , Insetos/enzimologia , Invertebrados/genética , Isoenzimas , Dados de Sequência Molecular , Conformação Proteica , Transcrição Genética , Tripsina/química , Tripsina/genética , Tripsinogênio/química , Tripsinogênio/genética
11.
Histopathology ; 50(5): 615-28, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17394498

RESUMO

AIMS: To establish the conditions for protein tyrosine phosphatase gamma (PTPgamma) detection in paraffin tissues using two antibodies raised against its NH(2)- (anti-P4) and COOH-termini (gammaTL1); to analyse its expression in normal tissues and to perform an initial screening of neoplastic tissues. METHODS AND RESULTS: Membranous and/or cytoplasmic PTPgamma expression was detected in the majority of epithelial cell types and in endocrine cells, with the highest expression in adrenal medulla, endocrine cells of the gastrointestinal tract and pancreatic islets. Both antibodies stained the thyroid follicular epithelium, but only anti-P4 antibody stained the colloid matrix, suggesting shedding/secretion of the PTPgamma extracellular domain. Marked loss of PTPgamma immunoreactivity was detected in subsets of ovarian (21%), breast (56%) and lung (80%) neoplasms. Conversely, cytoplasmic positivity was found in 37% of lymphomas, mainly of high-grade histotypes, while normal lymphocytes were negative. Brain tissue showed PTPgamma expression in a few neuronal and glial elements and PTPgamma was overexpressed in the majority of high-grade astrocytomas. CONCLUSIONS: We have analysed PTPgamma expression in archival paraffin-embedded tissues for the first time, demonstrating particularly high expression in endocrine cells and both down- and up-regulation in neoplasia, the latter possibly reflecting the undifferentiated state of the neoplastic cells, suggesting a complex role for this phosphatase.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias/enzimologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Receptores de Superfície Celular/metabolismo , Regulação para Baixo , Sistema Endócrino/citologia , Sistema Endócrino/enzimologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Masculino , Neoplasias/genética , Neoplasias/patologia , Proteínas do Tecido Nervoso/genética , Proteínas Tirosina Fosfatases/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/análise , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores , Receptores de Superfície Celular/genética , Regulação para Cima
12.
Nat Chem Biol ; 2(9): 486-93, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16906150

RESUMO

Nitrite represents a bioactive reservoir of nitric oxide (NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO with hemoglobin to form nitrate. Indeed, the formation of nitrite from NO in the blood is limited when plasma is substituted with physiological buffers, which suggests that plasma contains metal-based enzymatic pathways for nitrite synthesis. We therefore hypothesized that the multicopper oxidase, ceruloplasmin, could oxidize NO to NO+, with subsequent hydration to nitrite. Accordingly, plasma NO oxidase activity was decreased after ceruloplasmin immunodepletion, in ceruloplasmin knockout mice and in people with congenital aceruloplasminemia. Compared to controls, plasma nitrite concentrations were substantially reduced in ceruloplasmin knockout mice, which were more susceptible to liver infarction after ischemia and reperfusion. The extent of hepatocellular infarction normalized after nitrite repletion. These data suggest new functions for the multicopper oxidases in endocrine NO homeostasis and nitrite synthesis, and they support the hypothesis that physiological concentrations of nitrite contribute to hypoxic signaling and cytoprotection.


Assuntos
Ceruloplasmina/metabolismo , Sistema Endócrino/fisiologia , Homeostase/fisiologia , Óxido Nítrico Sintase/sangue , Óxido Nítrico/fisiologia , Nitritos/sangue , Animais , Catálise , Ceruloplasmina/genética , Sistema Endócrino/enzimologia , Sistema Endócrino/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Homeostase/efeitos dos fármacos , Homeostase/genética , Humanos , Técnicas In Vitro , Fígado/irrigação sanguínea , Masculino , Camundongos , Camundongos Transgênicos , Óxido Nítrico Sintase/metabolismo , Nitritos/uso terapêutico , Oxirredução , Plasma/enzimologia , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
13.
Am J Physiol Heart Circ Physiol ; 291(5): H2026-35, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16798825

RESUMO

Accumulating evidence suggests that the simple and ubiquitous anion salt, nitrite (NO(2)(-)), is a physiological signaling molecule with potential roles in intravascular endocrine nitric oxide (NO) transport, hypoxic vasodilation, signaling, and cytoprotection after ischemia-reperfusion. Human and animal studies of nitrite treatment and NO gas inhalation provide evidence that nitrite mediates many of the systemic therapeutic effects of NO gas inhalation, including peripheral vasodilation and prevention of ischemia-reperfusion-mediated tissue infarction. With regard to nitrite-dependent hypoxic signaling, biochemical and physiological studies suggest that hemoglobin possesses an allosterically regulated nitrite reductase activity that reduces nitrite to NO along the physiological oxygen gradient, potentially contributing to hypoxic vasodilation. An expanded consideration of nitrite as a hypoxia-dependent intrinsic signaling molecule has opened up a new field of research and therapeutic opportunities for diseases associated with regional hypoxia and vasoconstriction.


Assuntos
Hipóxia Celular , Citoproteção , Sistema Endócrino/fisiologia , Óxido Nítrico/fisiologia , Nitritos/farmacologia , Vasodilatação/fisiologia , Animais , Sistema Endócrino/enzimologia , Sistema Endócrino/metabolismo , Hemoglobinas/fisiologia , Humanos , Modelos Biológicos
14.
Asian J Surg ; 29(1): 31-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16428096

RESUMO

METHODS: We performed a urinary tract obstruction (UTO) surgical procedure at 93-107 days' gestation in lambs to investigate the relationship between pulmonary hypoplasia and the appearance of pulmonary endocrine cells by quantitative analysis of respiratory tract cells using light microscopic immunohistochemistry. RESULTS: UTO produced a significant reduction in lung weight, lung/body weight ratio, air capacity, air capacity/body weight ratio (p < 0.01) and radial alveolar count (p < 0.05), which indicated the presence of lung hypoplasia. These foetuses also showed a significant increase in the number of neuron-specific enolase (NSE)-positive pulmonary endocrine cells, expressed as the number of NSE-positive cells per bronchus (p < 0.01) or bronchiole (p < 0.05), the number of NSE-positive cells per unit perimeter of bronchus or bronchiole (p < 0.01), and the number of NSE-positive cells per unit bronchial or bronchiolar surface area (p < 0.01). CONCLUSION: These results suggest that UTO significantly retards and modifies the structural growth and functional development of pulmonary endocrine cells in NSE expression. We speculate that pulmonary endocrine cells and their mediators may play a role in the problems associated with UTO during intrauterine life.


Assuntos
Sistema Endócrino/patologia , Pulmão/anormalidades , Pulmão/patologia , Obstrução Uretral/embriologia , Animais , Modelos Animais de Doenças , Sistema Endócrino/enzimologia , Feminino , Pulmão/enzimologia , Fosfopiruvato Hidratase/metabolismo , Gravidez , Ovinos
15.
J Steroid Biochem Mol Biol ; 86(2): 151-8, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14568566

RESUMO

Insulin-like growth factor I (IGF-I) is important for gonadal and reproductive functions in mammals, although the physiological role of this growth factor during gonadal development in rodents remains largely unknown. Here, we examined the steady-state levels of IGF-I mRNA by the reverse transcriptase polymerase chain reaction (RT-PCR). IGF-I protein expression was also detected by Western blot. The effect of IGF-I as promoter of 17alpha-hydroxylase/C17-20 lyase and 17beta-hydroxysteroid dehydrogenase enzyme activity in vitro was evaluated by radioimmunoassay. Onset of IGF-I gene expression was on day E10 (urogenital ridge stage). IGF-I mRNA expression was markedly reduced on days E12 and E13 (testicular differentiation stage). IGF-I transcripts increased on day E14 and their transcription levels were maintained throughout the stages analyzed. Several IGF-I protein bands of 31-100 kDa were observed. Culture experiments demonstrated that 17alpha-hydroxyprogesterone and testosterone (T) secretion levels increased in the presence of IGF-I on days E11-E17. Additive effects of IGF-I plus (Bu)2cAMP were also seen during testicular development. It is proposed that IGF-I regulates the expression of key steroidogenic enzymes important for endocrine activity of the testis during prenatal development leading to establishment of the male phenotype and fertility.


Assuntos
Sistema Endócrino/metabolismo , Fator de Crescimento Insulin-Like I/fisiologia , Testículo/embriologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Embrião de Mamíferos , Sistema Endócrino/embriologia , Sistema Endócrino/enzimologia , Idade Gestacional , Gônadas , Fator de Crescimento Insulin-Like I/análise , Masculino , Camundongos , Camundongos Endogâmicos , RNA Mensageiro/análise , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/metabolismo , Testosterona/biossíntese
16.
J Cell Physiol ; 197(2): 189-97, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14502558

RESUMO

The importance of renal and hepatic gluconeogenesis in glucose homeostasis is well established, but the cellular localization of the key gluconeogenic enzymes liver fructose-1,6-bisphosphatase (FBPase) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in these organs and the potential contribution of other tissues in this process has not been investigated in detail. Therefore, we analyzed the human tissue localization and cellular distribution of FBPase and PEPCK immunohistochemically. The localization analysis demonstrated that FBPase was expressed in many tissues that had not been previously reported to contain FBPase activity (e.g., prostate, ovary, suprarenal cortex, stomach, and heart). In some multicellular tissues, this enzyme was detected in specialized areas such as epithelial cells of the small intestine and prostate or lung pneumocytes II. Interestingly, FBPase was also present in pancreas and cortex cells of the adrenal gland, organs that are involved in the control of carbohydrate and lipid metabolism. Although similar results were obtained for PEPCK localization, different expression of this enzyme was observed in pancreas, adrenal gland, and pneumocytes type I. These results show that co-expression of FBPase and PEPCK occurs not only in kidney and liver, but also in a variety of organs such as the small intestine, stomach, adrenal gland, testis, and prostate which might also contribute to gluconeogenesis. Our results are consistent with published data on the expression of glucose-6-phosphatase in the human small intestine, providing evidence that this organ may play an important role in the human glucose homeostasis.


Assuntos
Sistema Digestório/enzimologia , Sistema Endócrino/enzimologia , Frutose-Bifosfatase/metabolismo , Genitália Masculina/enzimologia , Gluconeogênese/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Sistema Digestório/citologia , Sistema Endócrino/citologia , Células Epiteliais/citologia , Células Epiteliais/enzimologia , Genitália Masculina/citologia , Humanos , Intestino Delgado/citologia , Intestino Delgado/enzimologia , Rim/citologia , Rim/enzimologia , Fígado/citologia , Fígado/enzimologia , Pulmão/citologia , Pulmão/enzimologia , Masculino
17.
Usp Fiziol Nauk ; 34(2): 3-20, 2003.
Artigo em Russo | MEDLINE | ID: mdl-12754787

RESUMO

Research of recent years has fundamentally revised modern endocrinology. Many organs and tissue that have never before been treated as endocrinal or involved in production of various hormones, became such. In particular, adipose tissue secreting to blood an important hormone--leptin--became the study object of particular interest.


Assuntos
Sistema Endócrino/enzimologia , Leptina/fisiologia , Tecido Adiposo/enzimologia , Animais , Proteínas de Transporte/fisiologia , Doenças do Sistema Endócrino/enzimologia , Humanos , Sistema Hipotálamo-Hipofisário/enzimologia , Peptídeos e Proteínas de Sinalização Intracelular , Leptina/genética , alfa-MSH/metabolismo , alfa-MSH/fisiologia
18.
Mech Ageing Dev ; 124(4): 371-8, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12714242

RESUMO

Metallothionein-III (MT-III) a brain-specific member of metallothionein family contributes to zinc neuronal homeostasis, and zinc is an important regulator of many brain functions, including the activity of hormone realising factors by hippocampus. Among them, somatostatin is pivotal because affecting thyroid hormones turnover and consequently thymic and peripheral immune efficiency (Natural Killer, NK) cell activity. Somatostatin is in turn affected by somatomedin-C, which is also zinc-dependent. Therefore, somatomedin-C may be a marker of somatostatin status in the hippocampus. MTs sequester and release zinc in transient stress, as it may occur in young age, to protect cells by reactive oxygen species. In order to accomplish this task, MTs are induced by IL-6 for a prompt immune and anti-inflammatory response. During ageing, MTs are high with a role of sequester of zinc, but with very limited role in zinc release because stress-like condition and inflammation is persistent. Therefore, high MTs may become to protective in young age to harmful during ageing leading to low zinc ion bioavailability for many body homeostatic mechanisms, including brain function. As a consequence, an altered physiological cascade from the brain (upstream) to endocrine and immune system (downstream) may occur. The aim of this work is to study the role of MT-III in the interrelationships among brain-endocrine-immune response in ageing and successful ageing. The main results are: (1) MT-III and IL-6 gene expressions increase in the hippocampus from old mice, in comparison with young and very old mice. (2) Somatomedin-C plasma levels decrease in old mice in comparison with young and very old mice. (3) Low zinc ion bioavailability (tested by the ratio total thymulin/active thymulin) is coupled with altered thyroid hormone turnover and depressed IL-2 in old mice in comparison with young and very old mice. (4) 'In vitro' experiments display more increments on NK cells activity by adding zinc-bound active thymulin than T3 alone. In conclusion, low MT-III in the hippocampus from young and very old mice leads to good zinc ion bioavailability that it is upstream coupled with normal hippocampal function affecting downstream normal thyroid hormones turnover and satisfactory NK cell activity, via complete saturation of zinc-bound active thymulin molecules. Therefore, a correct MTs homeostasis is pivotal for brain-endocrine-immune response in order to reach successful ageing.


Assuntos
Envelhecimento/imunologia , Sistema Endócrino/imunologia , Hipocampo/imunologia , Proteínas do Tecido Nervoso/genética , Neuroimunomodulação/fisiologia , Envelhecimento/metabolismo , Animais , Células Cultivadas , Meios de Cultura/farmacologia , Sistema Endócrino/enzimologia , Expressão Gênica , Hipocampo/enzimologia , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Interleucina-6/genética , Isomerismo , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Fator Tímico Circulante/metabolismo , Fator Tímico Circulante/farmacologia , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Zinco/metabolismo , Zinco/farmacologia
19.
Toxicol Appl Pharmacol ; 174(2): 160-76, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11446832

RESUMO

A two-year study on perch (Perca fluviatilis) in Lake Molnbyggen, Sweden, located in a pristine area but with a public refuse dump in the vicinity, has been conducted. The mechanistic approach through a set of biomarkers during the first year included age, condition, somatic growth, liver, gonad, and spleen weights, and a number of other physiological variables, in addition to ethoxyresorufin O-deethylase, glutathione-S-transferase, glutathione reductase, catalase, and the formation of DNA adducts in the liver. Perch from the uncontaminated Lake Djursjön, located in a neighboring drainage area, were used as reference fish. The most pronounced effect was a 80% reduction in the gonadosomatic index (GSI) for females and a corresponding 36% reduction in males. Fin erosion and shallow open sores were also frequently observed. Biomarkers and later chemical analysis employed indicated that exposure to well-known environmental pollutants was low, suggesting that less well-known antrophogenic substances are responsible for the effects observed in perch from Lake Molnbyggen. During the second year, roach (Rutilus rutilus) of both sexes were also included in this study. In addition, aromatase (P450arom) activity in the brain and testosterone and 17beta-estradiol levels in blood plasma were analyzed. Only one-fourth of the female perch were found to be sexually mature, which was associated with decreased GSI, lower P450arom activity, and reduced circulating levels of steroids. The reproductive disorders observed indicates disturbed endocrine function(s), arresting the majority of the female perch in a sexually nonreproducible immature stage. This novel study is the first to report evidence for endocrine disruption in wild populations of fish living in a lake exposed to leakage water from a public refuse dump.


Assuntos
Cyprinidae/fisiologia , Sistema Endócrino/efeitos dos fármacos , Percas/fisiologia , Eliminação de Resíduos , Poluentes da Água/toxicidade , Animais , Aromatase/efeitos dos fármacos , Aromatase/metabolismo , Peso Corporal/efeitos dos fármacos , Adutos de DNA/efeitos dos fármacos , Adutos de DNA/metabolismo , Sistema Endócrino/enzimologia , Sistema Endócrino/lesões , Sistema Endócrino/metabolismo , Estradiol/metabolismo , Feminino , Sedimentos Geológicos/análise , Masculino , Suécia , Testosterona/metabolismo , Xenobióticos/metabolismo
20.
J Pathol ; 185(3): 236-45, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9771476

RESUMO

The c-erbB-4/HER4 receptor belongs to the family of the type I growth factor receptors. Mouse monoclonal antibodies have been raised to the cytoplasmic domain of the c-erbB-4 receptor and characterized; the antibody HFR-1 has been used to determine the pattern of expression of the c-erbB-4 protein immunohistochemically in formalin-fixed, paraffin-embedded adult and fetal tissues. The expression of c-erbB-4 mRNA was determined by using 35S-labelled riboprobes and tissue in situ hybridization. c-erbB-4 is widely expressed in many adult and fetal tissues, including the lining epithelia of the gastrointestinal, urinary, reproductive, and respiratory tracts, as well as the skin, skeletal muscle, circulatory, endocrine, and nervous systems. The developing brain and heart notably express high levels of this receptor. The pattern of c-erbB-4 protein expression is also reported in a survey of common solid human cancers. Loss of expression was noted in 40-80 per cent of adenocarcinomas and up to 100 per cent of squamous cell carcinomas, whereas overexpression was observed in about 10-20 per cent of adenocarcinomas and astrocytomas. In general, the pattern of c-erbB-4 expression in normal tissues and cancers suggests that it tends to be associated with the differentiated compartment.


Assuntos
Sistema Cardiovascular/enzimologia , Receptores ErbB/análise , Feto/enzimologia , Neoplasias/enzimologia , Sistema Nervoso/enzimologia , RNA Mensageiro/análise , Adenocarcinoma/enzimologia , Adulto , Animais , Anticorpos Monoclonais , Mama/enzimologia , Carcinoma de Células Escamosas/enzimologia , Sistema Digestório/enzimologia , Sistema Endócrino/enzimologia , Epitélio/enzimologia , Receptores ErbB/genética , Receptores ErbB/imunologia , Glioblastoma/enzimologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Sistema Musculoesquelético/enzimologia , Coelhos , Receptor ErbB-4 , Sistema Respiratório/enzimologia , Pele/enzimologia , Sistema Urogenital/enzimologia
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