Leptin as a Modulator of Neuroendocrine Function in Humans

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.

Leptina e o controle neuroendócrino do peso corporal / Leptin and the neuroendocrine control body weight

A obesidade nos últimos anos vem sendo tratada como um problema de saúde pública, despertando grande interesse nos profissionais da saúde. Compreender o papel da leptina no controle neuroendócrino da ingestão de nutrientes, do gasto energético, depósito de gorduras e do peso corporal é objetivo de um número crescente de pesquisadores, visto que este é um hormônio com papel relevante na interação entre os adipócitos e os neurônios.Nesta revisão atualizamos aspectos como a estrutura da leptina, local e fatores que influenciam na sua síntese, tecidos que expressam receptores e mecanismos de ação. Enfatizamos a ação da leptina no hipotálamo, sítio em que ocorre o controle da ingestão alimentar, com foco em novas perspectivas de intervenção farmacológica no sentido de favorecer maior equilíbrio entre o metabolismo e a ingestão alimentar.

Effect of simulated ascent to 3500 meter on neuro-endocrine functions.

Ascent to extreme High Altitude (HA) is in steps and it entails acclimatization at moderately HA locations. In terms of acclimatization, it is pertinent to understand the physiological changes, which occur on immediate ascent to moderate HA. The study aimed to evaluate the effect of ascent to 3500 m on neuro-endocrine responses in the first hour of induction. The plasma levels of catecholamines and cortisol were measured before and after one hour of ascent to high altitude. The peripheral oxygen saturation (SpO2), Galvanic Skin Resistance (GSR), Heart Rate (HR) and Blood Pressure (BP) were simultaneously monitored. The plasma epinephrine, norepinephrine, dopamine and cortisol were increased after one-hour exposure to 3500 m altitude as compared to before exposure. The SpO2 showed a significant decrease during and after high altitude induction. The heart rate and diastolic BP increased at 3500 m whereas the GSR did not show significant changes. There are changes in neuroendocrine responses, which reflect a sympathetic over activity in the first hour of exposure to 3500 m.

Ghrelin; Influences on Helicobacter pylori-associated Gastric Diseases / 대한소화기학회지

Recently, gastric Helicobacter pylori (H. pylori) colonization has been shown to affect the expression of leptin and ghrelin, hormones that control appetite and satiety. Gastric leptin, produced by chief and parietal cells and released in response to meals, may play a role in weight gain after eradication of H. pylori infection, whereas ghrelin, produced by X/A-like enteroendocrine cells in oxyntic gland, is released during fasting, and suppressed by feeding and leptin. Whether either that H. pylori genes represent microbial contributions to the complement of thrifty genes of humans, or that H. pylori disappearance plays a role in adiposity remains to be determined. Simply, ghrelin-leptin might tango in body weight regulation, gastric inflammation, and gastric motility. In the current review about the possible role of ghrelin in gastric inflammation, we found that high serum albumin condition decreased ghrelin expression, whereas serum albumin deprivation significantly increased ghrelin expression, however, of which regulation was abolished after H. pylori infection. Ghrelin significantly attenuated the inflammatory stimuli imposed after H. pylori, shown with inactivation of phospho-extracellular signal-regulated kinase (p-ERK) and nuclear factor-KappaB (NF-KappaB)-DNA binding activities. Conclusively, besides orexigenic and weight gaining actions of gastric hormone, ghrelin, it likely endows the stomach the protective effect from exogenous damages.

M3 Subtype of Muscarinic Receptors Mediate Ca2+ Release from Intracellular Stores in Rat Prostate Neuroendocrine Cells

Our previous studies document the expression of adrenoceptors and purinoceptors in the rat prostate neuroendocrine cells (RPNECs). However, a direct investigation of the receptors for acetylcholine (ACh) is still lacking in the prostate neuroendocrine cells. RPNECs were freshly isolated from the ventral lobes of rat prostate by using collagenase. Effects of ACh and various muscarinic antagonists on the intracellular Ca2+ concentration ([Ca2+]c ) were investigated by using the fura-2 spectrofluorimetry. Single-cell RT-PCR analysis was applied to identify the transcripts for the muscarinic receptor subtypes. ACh (5 micrometer) induced a sharp transient increase in the [Ca2+]c of RPNECs, which was independent of the extracellular Ca2+. In the same RPNECs, high KCl (60 mM), phenylephrine (5micrometer), UTP (P2Y1/2 agonist, 50, micrometer), and alpha, beta-meATP (P2X1/3 agonist, 0.5micrometer) also increased the [Ca2+]c. The ACh-induced [Ca2+]c change (delta[Ca2+]c ) was blocked by atropine or by para-fluorohexahydrosiladifenidol (M3 antagonist, 0.3micrometer), but not by telenzepine (M1 antagonist, 1 micrometer) and himbacine (M2 and M4 antagonist, 1 mircoM). The single-cell RT-PCR demonstrated the selective expression of mRNAs for M3 in RPNECs. In summary, RPNECs express M3 muscarinic receptors that are linked to the release of Ca2+ from intracellular stores. The Ca2+ signals of RPNECs might mediate the parasympathetic regulation of prostate gland.

Aspectos neuroendocrinos de la obesidad / Neuroendocrine aspects of obesity

En la fisiopatología de la obesidad intervienen factores genéticos, sociales, metabólicos, endocrinos y neurológicos. Esta multifactoriedad junto al hecho que estos factores se interrelacionan a través de mecanismos muy complejos, que son sólo parcialmente conocidos, ha llevado a que la comprensión íntima de este trastorno resulte una tarea sumamente ardua. Por estos motivos, el conocimiento integral de esta afección plantea un desafío al que actualmente están abocados numerosos grupos de investigadores. El análisis de la obesidad como un trastorno neuroendocrino, propone el estudio de este fenómeno desde una visión particular que implica disfunciones en casi todos los órganos endocrinos y en el sistema nervioso central, fundamentalmente en la actividad hipotalámica. Estas alteraciones afectan principalmente a los ejes neuroendocrinos hipotálamo-hipofiso-adrenal, adipo-insular y al control hipotalámico, tanto de la ingesta de alimento como del almacenamiento y gasto energético. Este artículo plantea una actualización en este campo; en primer lugar, se realiza una breve descripción, en forma independiente, de los principales sistemas antes mencionados y luego una descripción de su funcionamiento normal integrado. Finalmente, se describen desregulaciones de estos mecanismos y se discute como ellas contribuirían al desarrollo y/o mantenimiento de la obesidad.

Anestesia e resposta neuroendócrina e humoral ao estresse cirúrgico / Anesthesia and neuroendocrine and humoral responses to surgical stress

Justificativa e Objetivos: A resposta neuroendócrina e metabólica ao estresse é um mecanismo de defesa do organismo agredido por trauma psicológico, físico ou cirúrgico e tem sido objeto de vários trabalhos científicos. O objetivo deste trabalho é enfocar os aspectos relativos à resposta neuroendócrina-metabólica e imunalógica ao trauma cirúrgico, procurando proporcionar conhecimentos para possibilitar a modulaçäo desta resposta através da anestesia. Conteúdo: Säo apresentados os mecanismos e a fisiopatologia da ativaçäo da resposta neuroendócrina e metabólica, assim como as fases da resposta ao estresse cirúrgico. Säo abordadas as várias técnicas de anestesia e adjuvantes empregados na modulaçäo da resposta neuroendócrina à cirurgia, desde a consulta pré-anestésica. Conclusöes: Devido a alta complexidade dos mecanismos envolvidos e a inexistência de técnicas anestésicas isoladas que sejam capazes de bloquear a resposta neuroendócrina e metabólica a tendência atual é de se utilizar associaçöes de técnicas para se obter melhores resultados

El perfil neuroendocrino especifico es critico para una correcta respuesta inmune T-dependiente / The specific neuroendocrine profile is critically involved in an adequate T-dependent immune response

Existe una relación funcional entre los sistemas neuroendocrino e inmune. Examinamos el rol de los cambios neuroendocrinos, particularmente hormona liberadora de tirotrofina (TRH) y prolactina (PRL), durante el curso de la respuesta inmune T-dependiente. En ratas inmunizadas ip con eritrocitos de carnero (SRBC, antígeno T-dependiente), se observó: a) un incremento del ARNm de TRH hipotalámica entre las 4 y 24 h post-inmunización (ej: SRBC vs salina: 4 h, 2,8x), en contraste a una disminución del ARNm de TRH observado por tratamiento con antígenos T-independientes (ej: LPS vs salina: 4 h, 1,6x); b) un incremento del ARNm del receptor de TRH y de los niveles de PRL plasmática sin observarse cambios, en los niveles plasmáticos de hormona de crecimiento y tirotrofina. La inyección intracerebroventricular (icv) en ratas conscientes y en movimiento de oligonucleótidos antisentido al mRNA de TRH produjo: a) una inhibición en la producción de anticuerpos anti-SRBC [ELISA 7 días: Ig(M+G): TRH sentido vs TRH-antisentido: 384 + 27 vs 193 + 22 (n = 11); p < 0.001, ANOVA con test de Scheffé's]; b) una incapacidad en producir el pico de liberación de PRL luego de la inmunización (12 h post-inmunización, TRH-sentido vs TRH-antisentido: 8.3 + 1.4 vs 2.2 + 0.5 (n = 6), p < 0.01, ANOVA con test de Scheffé's); c) una dismunución del ARNm de TRH hipotalámica (TRH-sentido vs TRH-antisentido: 12 h, 1.7x). Estos estudios demuenstran que un antígeno T-dependiente requiere de una activación temprana de TRH y PRL, instrumental para montar una respuesta adecuada, en contraste a la inhibición inducida por antígenos T-independientes.

Interaçäo imuno neuro endócrina / Neuroendocrine and immunological interactions

O sistema imune, tido como aquele que defende o organismo humano contra agressoes externas e endógenas, é visto, hoje, num âmbito mais amplo quando consideramos a homeostase. Ele apresenta íntima inter-relaçao com o sistema nervoso e endócrino. Uma complexa e intrincada rede de comunicaçao existe entre estes três sistemas, onde receptores e substancias sao produzidas e compartilhadas. O conhecimento desta interaçao entre sistemas pode ser a resposta para o aparecimento de alteraçoes endócrinas em pacientes sem uma patologia endócrina específica, para modificaçoes da capacidade de resposta a infecçoes e progressao de doenças neoplásicas e para a influência no curso das doenças auto-imunes. Nesta revisao realizamos uma abordagem sobre a interaçao entre o sistema imune, nervoso e endócrino e implicaçoes clínicas.

Respuesta endócrino-metabólica neonatal a la cirugía / Neonatal endocrine and metabolic response to surgery

Con el propósito de describir la respuesta endócrino-metabólica a la cirugía (REMC) en el neonato y de enfatizar la importancia de su conocimiento para hacer racional el tratamiento y cuidados perioperatorios en este grupo de pacientes, se revisan las evidencias clínicas y experimentales de esta respuesta en este grupo de edad publicadas en los últimos diez años. Se describen los reflejos neuroendócrinos que inician la REMC en el neonato y se definen las características fundamentalmente del ambiente endócrino-metabólico neonatal postoperatorio. Además, se hacen consideraciones sobre su relevancia para determinar los cuidados perioperatorios del recién nacido. Se concluye que el neonato es capaz de establecer una REMC cualitativa y cuantitativamente diferente a la de otros grupos de edad, y que del conocimiento y comprensión de esta respuesta depende la calidad del tratamiento ofrecido al recién nacido quirúrgico