Control de la ingesta alimentaria: rol del receptor 4 de melanocortina en el desarrollo de obesidad / Role of melanocortin receptor 4 in the control of food intake and the development of obesity

Arquate nucleus, a convergence site of peripheral and central signals, plays a fundamental role in the control of food intake. Orexigenic neurons that secrete neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and anorexigenic neurons secreting Pro-opiomelanocortin (POMC) are involved in this action. Both groups of neurons respond to peripheral signals such as insulin and leptin and are reciprocally inhibited. alpha Type melanocyte stimulating hormone (alphaMSH), liberated by POMC neurons, reduces food intake activating melanocortin receptor 4 (MC4R), located in second order neurons of the paraventricular nucleus. NPY/AgRP antagonize the effects of this peptide on MC4R receptors,maintaining an inhibitory tone on áMHS liberation, mediated by the activation of gabaergic receptors of POMC neurons. The study of these mechanisms will allow the development of new medications, especially MC4R agonists, to reduce nutrient intake...

Mechanisms regulating melanogenesis* / Mecanismos reguladores da melanogênese

Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options.

A pigmentação da pele é um importante traço fenotípico do ser humano mas apesar dos recentes avanços a sua regulação não está ainda totalmente esclarecida. O pigmento melanina é produzido nos melanossomas pelos melanócitos, num processo complexo designado por melanogénese. O melanócito interatua com os sistemas endócrino, imunitário, inflamatório e nervoso central e a sua atividade é também regulada por fatores extrínsecos como a radiação ultravioleta e fármacos. Fizemos uma revisão do conhecimento atual sobre os fatores intrínsecos e extrínsecos reguladores da pigmentação cutânea, etapas da melanogénese e defeitos genéticos relacionados. Fizemos enfoque na interação melanócito-keratinócito, na ativação do receptor da melanocortina tipo 1 (MC1-R) pelos péptidos (hormona estimuladora do melanócito e hormona adrenocorticotrófica) resultantes da clivagem da proopiomelanocortina (POMC) e mecanismos da pigmentação induzida pela radiação ultravioleta. A identificação e compreensão dos mecanismos reguladores da pigmentação cutânea facilitam o conhecimento dos mecanismos patogénicos dos distúrbios da pigmentação e o desenvolvimento de potenciais opções terapêuticas.

The effect of melanocortin (Mc3 and Mc4) antagonists on serotonin-induced food and water intake of broiler cockerels

The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 microg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 microg serotonin. For Experiment 3, the chickens were given 10 microg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.

Diagnosis and Treatment of Unilateral Maxillary Sinus Hypoplasia

Research of cellular toxic effect to Hep-2 of recombinant toxin MSH-Ang / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the cytotoxicity of recombinate toxin MSH-Ang to Hep-2.@*METHOD@#The depurated MSH-Ang were applied in cytotoxicity experiment, and the growth inhibiting action to laryngeal carcinoma cell Hep-2 were observed.@*RESULT@#Recombination protein inhibited the growth of laryngeal carcinoma cell Hep-2, and its inhibiting action enhanced and corpuscular mortality rate increased along with the concentration increasing.@*CONCLUSION@#Recombinant toxin MSH-Ang can not only take special effect in tumors with high MSHR, but also target to many other popular tumors.

Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of Tribulus terrestris extract on melanocyte stimulating hormone (MSH) expression in C57BL/6J mouse hair follicles, and investigate the role of Tribulus terrestris extract in activation, proliferation, epidermal migration of dormant hair follicle melanocytes.</p><p><b>METHODS</b>The aqueous extract of Tribulus terrestris was administered orally in specific pathogen-free C57BL/6J mouse at the daily dose equivalent to 1 g/1 kg in adult human, and the expression and distribution of MSH in the mouse hair follicles was observed with immunohistochemistry.</p><p><b>RESULTS</b>The positivity rate of MSH expression in the hair follicle melanocytes was 75% in mice treated with the extract, significantly higher than the rate of only 18.75% in the control group (P<0.01).</p><p><b>CONCLUSION</b>The aqueous extract of Tribulus terrestris can significantly increase MSH expression in the hair follicle melanocytes by activating tyrosinase activity and promoting melanocyte proliferation, melanine synthesis, and epidermal migration of dormant melanocytes.</p>

Electron microscopical studies of pituitary gland of male hamsters under the effect of estrogen treatment

The ultrastructure of the normal pars intermedia of male hamsters showed two types of cells. The light cells were numerous, regular in shape with rounded or elongated nuclei have different size of secretory granules and were considered as a source of melanocyte stimulating hormone [MSH]. The dark cells were less in number, showed less display of secretory granules and were concerned with colloid production. Some of the dark cells showed foot like processes and irregular nuclear membranes. Progressive changes in the cell organelles were observed in the pars intermedia cells after long term of estrogen treated hamsters over the studied period

Changes in Incidence of Infantile Transient Methemoglobinemia Associated with Infectious Diarrhea during 1989-1999 in Kyungnam Province

PURPOSE: Infantile transient methemoglobinemia(ITM) may develop in association with infectious diarrhea without exposure to any toxic oxidizing agents. We observed that the number of ITM associated with infectious diarrhea have increased at the Gyeongsang National University Hospital (GNUH), located in the western area of Kyungnam province during the last 4 years. To determine whether this phenomenon was similarily observed in the rest of Kyungnam province, we studied the incidence of ITM associated with infectious diarrhea over the last 10 years in Kyungnam Provine. METHODS: All cases with ITM associated with infectious diarrhea were enrolled for this study from Ulsan Donggang Hospital(UDH), Masan Samsung Hospital(MSH), and GNUH over the last 10 years. Their medical records were reviewed retrospectively. RESULTS: Six and twelve cases were identified at UDH and GNUH, respectively, while none were identified at MSH. All the infants were less than 2 months of age and prosented with severe mucoid diarrhea with metabolic acidosis, high C-reactive protein(CRP) concentrations and/or leukocytosis with shift to left. Twelve cases were identified to reveal stool leukocytosis at UGH and GNUH. Eight cases had histories of ingestion of well water. Nine cases occurred in the spring season (May, April, March). Before 1996, a total of six cases occurred at UDH. But one case in 1990 and eleven cases occurred during 1996-99 at GNUH. The increase in the incidence of ITM associated with infectious diarrhea paralleled the increase in the infectious diarrhea in infants during 1996-99 at GNUH. CONCLUSION: The increased in the incidence of ITM associated with infectious diarrhea during the last4 years at GNUH was not observed in other parts of Kyungnam province. Infectious diarrhea, severe acidosis, severe dehydration, cow milk feeding, the spring season and ingestion of well water were considered to be important associateion factors of ITM.

The Effect of alpha-MSH on the Morphologic Changes, Survival, and Melanization of Cultured Human Melanocytes / 대한피부과학회지

BACKGROUND: The effects of melanocyte stimulating hormone(MSH) on the integument of many species, including mammals, are well known. The significance of MSH as a physiological regulator of cutaneous pigmentation in humans is still controversial. Although the administration of MSH results in skin darkening, previous reports suggest that cultured human melanocytes are relatively unresponsive to this peptide. This may be related to the conditions under which the melanocytes were cultured. OBJECTIVE: The purpose of this study was to investigate the effect of alpha-MSH on the morphological changes, survival, and melanization of cultured human melanocytes in a basal medium without any mitogen. METHOD: We examined the morphological changes, number and melanin contents of cultured human melanocytes in control(absence of alpha-MSH) and experimental groups(presence of 10(-8) M, 10(-7) M, and 10(-6) M alpha-MSH). RESULTS: 1. There were no significant morphological changes of cells between the control and experimental groups after 24, 48, and 72 hours' culture. The number and length of melanocyte dendrites showed no significant difference between the groups after 24, 48, and 72 hours' culture. 2. The number of melanocytes in the experimental groups(presence of 10(-7) M, and 10(-6) M alpha-MSH) were significantly higher than the number of melanocytes in control group after 72 hours culture(p<0.05). This effect of alpha-MSH was dose-related. 3. The melanin contents slightly increased in the experimental groups. The significant difference between the groups was showed in the presence of 10(-8) M alpha-MSH. CONCLUSIONS: alpha-MSH has no effect on the morphology, but increases the survival of cultured human melanocytes and has a melanogenic effect.

cytological effects of a neurotrophic peptide [MPF] in Parkinsonian rats

Substantia nigra [SN] samples from rats with 6-hydroxdopamine [6-OHDA] -induced lesions of right nigrostriatal pathways were retrieved and examined by transmission electron microscopy [TEM] 15-17 months after a single intrastriatal injection of a metabolically-stable analogue of Lys-Lys-Gly-Glu [MPF] in Krebs-Hensleitt buffer, given two weeks after the lesioning. The results were compared with those from control samples taken from rats which had been similarly lesioned and kept for 15-17 months, but which had received only Krebs-Hensleitt buffer, and with samples taken from two age matched, non-lesioned rats. Compared with the age matched, non-lesioned rats, there was a 37% overall loss of and extensive damage to all surviving SN neurons in samples from control rats [lesioned, buffer only]. There was widespread collapse of mitochondria [63% in the case of dopaminergic neurons], loss of cell membranes [in 4.4% of cases], myelin abnormalities [9.0%] and increased vacuolation [10.9%]. In contrast, most of the SN neurons from MPF-treated rats were healthy reflected in a high degree of cellular organization and integration; only 9.0% of the mitochondria were collapsed, and the cell membranes damage [2.9%] myelin abnormalities [1.5%], and the increased vacuolation [2.6%] were significantly less than found in the control rats. We have previously reported a significant reduction in the amphetamine-induced turning behaviour of lesioned rats following injection of the MPF analogue, beginning 6 weeks after the MPF injection, and reaching marked and consistent levels after 12 weeks. This time course, in conjunction with the present results and known neurotrophic properties of MPF, suggest that the favourable behavioural effects of MPF arise by restoration of nigrostriatal pathways

Cellular signalling in vertebrate pigment cells

Chromatophores are specialized integumental stellate cells that synthesize and store pigments. Pigment granules are translocated within chromatophores of poikilothermic vertebrates and crustaceans in response to photic, thermal and/or neurohormonal stimuli, allowing the animal to rapidly change color for thermoregulation, adaptation to light and background, and social behavior display. Birds and mammals do not show color changes, but may present slow long-term responses, such as melanocyte proliferation, melanin synthesis and melanin granule translocation into feathers, hair and surrounding keratinocytes. Pigment translocation in lower vertebrates as well as pigment production in all vertebrates are modulated by a variety of hormones and neurotransmitters acting on transmembrane receptors located on the cell surface. Alpha-melanocyte-stimulating hormone (alpha-MSH), melanin-concentrating hormone (MCH), melatonin and catecholamines are the most important pigment cell agonists in vertebrates. The major signalling pathway leading to pigment dispersion and melanin synthesis appears to involve stimulation of adenylate cyclase followed by an increase in the cAMP level and activation cAMP-dependent protein kinases (PKAs). Another melanogenesis related intracellular pathway involves the activation of protein kinase C (PKC) by diacylglycerol, and the increase in cytosolic Ca2+ by inositol triphosphate. Growth factors such as basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and mast cell growth factor (MGF or KIT tigand), and UV radiation modulate the melanogenic and mitogenic processes in vertebrates melanocytes as well.

Hypothalamic control of water and salt intake and excretion

This article provides a personal and historical review of research concerning the hypothalamic control of water and salt intake and excretion. The following major points will be considered: 1. Electrical, osmotic, cholinergic, alpha-adrenergic and peptidergic stimulation of the hypothalamus. 2. Determination of the pathways involved in these neuroendocrine responses. 3. The participation of ANP in the control of thirst and salt excretion. 4. The participation of the brain ANPergic neuronal system in ANP release. 5. The role of hypothalamic ANPergic neurons and of sinoaortic and renal baroreceptors in the regulation of volume expansion-induced release of ANP. 6. Effects of the brain ANP system on other hormones.

The influence of the blockade of alfa-melanotroprin (alfa-MSH) on the time of vaginal opening and on LH-RH release

Se obtuvo un anticuerpo específico contra alfa-MSH, conjugado el péptido con albúmina por medio del reactivo de carbodiimida. En este trabajo se establecen los efectos del bloqueo de alfa-MSH por su antisuero específico, en dos modelos fisiológicos: 1) bloqueio del pico sérico de alfa-MSH que se produce en el día 30 en ratas prepúberes y estaría relacionado con la apertura vaginal (AV). 2) el efecto del bloqueo in vitro de alfa-MSH (en eminencia media (EM) de animales en la mañana del proestro) sobre la liberación de LH-RH. La administración del antisuero a través de infusión cocntinua a ratas, desde el día 28 PN al 32 PN retrasa el tiempo de apertura vaginal. El bloqueo de alfa-MSH in vitro a nivel del sistema nervioso central, induce un incremento dosis-dependiente en la liberación de LH-RH al medio de incubación. Estos datos sugerirían que alfa-MSH podría actuar a través de dos vías en los mecanismos regulatorios de la reproducción, uno a nivel periférico y otro, central. En ratas hembras prepúberes, el pico sérico de alfa-MSH que ocurre el día 30, podria participar en la activación de la cadena de eventos, que culminan en la pubertad (nivel periférico). Alfa-MSH a nivel del sistema nervioso central en la rata hembra adulta, ejercería un efecto inhibidor directamente o como modulador de las terminales de EM, influenciando la liberacción de LH-RH (nivel central)

Modifications in alfa-MSH concentrations in different hypothalamic areas during the estrous cycle in the rat

Este trabajo fue realizado con el fin de 1) examinar las variaciones en la concentración de alfa-MSH en áreas hipolámicas a lo largo del ciclo estrual y 2) analizar si durante el ciclo el alfa-MSH que deriva de la proopiomelanocortina (POMC) tiene las mismas variaciones de concentración que el alfa-MSH que deriva del hipotálamo dorso lateral (HDL). La concentración de alfa-MSH en el hipotálamo mediobasal (HMB), área preóptica (APO) y HDL fue medida utilizando un radioinmunoensayo específico. Las ratas fueron sacrificadas cada cuatro horas mediante perfusión intracardíaca de solución fisiológica. Se observa un ritmo circadiano en todas las áreas estudiadas, excepto en HMB durante el estro. La concentración de alfa-MSH en HMB se mantuvo alta durante el período de luz a la inversa de lo que se observaba en el APO. En general cuando los niveles de alfa-MSH se encuentran elevados en HMB, se mantienen bajos en APO y viceversa. El perfil hallado en HDL es muy semejante al de APO. La acumulación de alfa-MSH en los cuerpos neuronales del sistema de la POMC, y su disminución en las fibras que provienen de dicho sistema durante la tarde del proestro, podrían relacionarse con la caracteristica liberación de LH y PRL que ocurre en ese momento

Release of LH in response to alpha-MSH administration

Efecto de alfa-MSH en la liberación de LH. Para obtener información sobre le posible mecanismo por el cual alfa-MSH modifica la secreción de gonadotrofinas se realizó el presente trabajo. El efecto del péptido sobre los niveles séricos de LH fue estudiados en varios modelos experimentales. La infusión de alfa-MSH en diestro 2 tarde induce al día siguiente una elevación en los niveles séricos de LH a las 18 h y en la mañana del estro las ratas así tratadas tienen un número mayor de óvulos que las ratas que recibieron solución fisiológica. Además cuando el péptido se administra en ratas ovariectomizadas crónicas que reciben benzoato de estradiol más dosis de 40 ug de porgesterona (P), ésta incrementa los niveles de LH al igual que los de P. Ha sido demostrado que la ovariectomía y adrenalectomía en la tarde del proestro bloques el pico de LH en suero, sin embargo la inyección de alfa-MSH momentos antes de la operación permite que este pico se produzca. Cuando se miden los niveles de P séricas en estos animales se observa que permanecen por más tiempo en suero cuando se los compara con los animales que han recibido solución fisiológica. Por otro lado cuando alfa-MSH se infunde en ratas crónicamente ovariectomizadas que han recibido dosis muy bajas de benzoato de estradiol, que de por sí solas disminuyen los niveles de LH en el péptido puede disminuirlos aún más, y cuando se miden los niveles de P éstos han aumentado. Finalmente, alfa-MSH no modifica los niveles de LH en el día del diestro. Los resultados recién comentados demuestran que alfa-MSH influencia la liberación de LH como consecuencia de la modificación de la liberación y/o degradación de P. Esta P sería la responsable de la modificación de los niveles de LH en suero, teniendo un efecto estimulatorio o inhibitorio sobre la liberación de LH dependiendo del tiempo en que permanece alta en suero

Función adaptativa de MSH, potenciales cerebrales y atención selectiva en el hombre / The adaptative function of MSH, brain potentials and selective attention in man

Se valoró el efecto de la hormona estimulante de melanocitos (MSH) sobre la atención selectiva en el hombre por medio de los cambios de amplitud en los componentes temprano y tardío de los potenciales somáticos evocados (PSE). Se tuvo cuidado especial de valorar los cambios concomitantes en el nivel de alerta general y en las pruebas de memoria reciente o de discriminación espacial. Este efecto se comparó con los producidos por fármacos del tipo de la noradrenalina (dextroanfetamina) y morfínicos (fentanil y naloxona). Ninguno de estos compuestos cambió la amplitud de los PSE tempranos, pero modificaron de manera diferencial los tardíos; la MSH y la naloxona aumentaron la amplitud de los PSE tardíos, en tanto que la dextroanfetamina y el fentanil la disminuyeron. La MSH y la naloxona aumentaron la velocidad de reacción, lo mismo que las pruebas de retención visual y discriminación espacial, sin cambios en el nivel de alerta general. La dextroanfetamina y el fentanil disminuyeron las pruebas de retención visual o de discriminación espacial, pero en tanto la primera aumentó la velocidad de reacción y el estado de alerta general, la última disminuyó la velocidad de reacción sin producir cambios en el estado de alerta general. Estos dados sugieren que MSH y otros compuestos relacionados producen cambios en el proceso de la atención del hombre al modificar la excitabilidad de los componentes tardíos de los PSE mediadores del sistema extralemniscal, pero no los propios del sistema lemnisco. Sugieren además que los cambios producidos en los PSE por MSH, fentanil y naloxona ocurrieron a nivel cortical pero no en la parte reticular del sistema extralemniscal, puesto que estos compuestos modificaron la velocidad de reacción y las pruebas de retención visual o de discriminación espacial (parte cortical) sin cambios en el nivel de alerta general (parte reticular). Sin embargo, los cambios producidos por la destroanfetamina en los PSE tardíos y la atención, deben considerarse consecuencias de la activación de los circuitos reticular y motor, que son independientes del relacionado con la atención selectiva

Release of alpha-MSH from the in vitro superfused neuro-intermediate lobe of the pituitary of the rat by antidiuretic hormone.

The effect of antidiuretic hormone (ADH) on the release of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSH) from the superfused neurointermediate lobe of the pituitary of the normal Wistar and Brattleboro (diabetes insipidus) rat was studied in vitro. In control experiments, there was usually an initial peak, after which alpha-MSH release fell exponentially over the course of the perfusion. Following the addition of ADH, the levels of alpha-MSH in the superfusate showed a significant rise. It is suggested that ADH is normally involved in the secretion of alpha-MSH by the pars intermedia of the rat, especially in response to osmotic stimuli.