RESUMO
PURPOSE: Liver-expressed antimicrobial peptide 2 (LEAP-2) has been recently identified as the endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). In rodents, LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status, being decreased upon fasting and increased in high-fat diet (HFD) fed mice. Clinical data support the regulation of circulating LEAP-2 by nutrient availability in humans. In this work, our primary objective was to examine the chronic effects of ghrelin and LEAP-2 administration on food intake, adiposity, and energy expenditure in young mice subjected to standard and HFD at both room temperature and at thermoneutrality. Furthermore, we aimed to assess the impact of these two hormones on aging mice. RESULTS: Our results indicate that LEAP-2 produces a significant decrease of body weight and adiposity, an increase in energy expenditure, and activation of the thermogenic program in white and brown adipose tissue depots. However, this effect is not maintained under HFD or under thermoneutral conditions and is only partially observed in aging mice. CONCLUSION: In summary our studies describe the central effects of LEAP-2 within distinct experimental contexts, and contribute to the comprehension of LEAP-2's role in energy metabolism.
Assuntos
Envelhecimento , Dieta Hiperlipídica , Metabolismo Energético , Grelina , Homeostase , Animais , Grelina/farmacologia , Grelina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Envelhecimento/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Masculino , Peptídeos Catiônicos Antimicrobianos/metabolismo , Camundongos Endogâmicos C57BL , Termogênese/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Adiposidade/fisiologia , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Proteínas SanguíneasRESUMO
PURPOSE: Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. METHODS: Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. RESULTS: Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. CONCLUSIONS: Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.
Assuntos
Mucosa Intestinal/metabolismo , Leptina/farmacologia , Peptídeos Natriuréticos/sangue , Estado Nutricional , Animais , Dieta Hiperlipídica , Metabolismo Energético , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Peptídeos Natriuréticos/genética , Regulação para CimaRESUMO
In this study, we compare the effects of pre- and post-natal food deprivation on the relative proportion of fibre types and contractile responses in the extensor digitorum longus (EDL) muscle of female and male rats at different post-natal ages. EDL muscles from undernourished male (UM) rats showed a higher proportion of Type IIB than IIA fibres and larger normalized twitch responses (with respect to muscle weight) than those of controls (CM). In contrast, EDL muscles from control (CF) and undernourished female rats (UF) showed no significant differences in their fibre type composition and normalized twitch forces at most of the ages analysed. Our data are indicative that the EDL muscles from undernourished males are more susceptible to the effects exerted by low food income than the EDL muscles from female rats. It is proposed that changes in the reactive oxygen species (ROS) concentration and hormonal factors, due to undernutrition, are involved in the alterations observed in the fibre type composition and force production of EDL muscles in undernourished male rats and that estrogens may have an antioxidant protective role on the undernourished EDL muscles in female rats.
Assuntos
Desnutrição , Fibras Musculares de Contração Rápida/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ingestão de Alimentos , Ingestão de Energia , Feminino , Privação de Alimentos/fisiologia , Masculino , Ratos , Ratos WistarRESUMO
Ghrelin, the endogenous ligand of GH secretagogue receptor type 1a, has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and, recently, reproduction. Although inhibitory actions of ghrelin on LH secretion and puberty onset have been reported previously, the receptor mechanisms mediating these actions, and the potential gonadotropic effects of the unacylated isoform of ghrelin (UAG), remain unclear. In this work, the effects of single and repeated administration of ghrelin or UAG on LH secretion were compared in pubertal and adult male rats. In addition, the effects of ghrelin were assessed in models of transient or persistent hypergonadotropism. Daily injection of ghrelin or UAG throughout puberty similarly decreased LH levels and partially delayed balanopreputial separation. Likewise, chronic infusion of ghrelin or UAG to adult males resulted in significant decreases in circulating LH and FSH concentrations. Moreover, acute injection of ghrelin induced a transient reduction in LH levels in freely moving males, an effect that was fully mimicked by administration of UAG. Yet in contrast to ghrelin, UAG failed to modify GH secretion. Finally, injection of ghrelin moderately, but significantly, reduced the duration of LH secretory responses to the potent gonadotropin secretagogue kisspeptin-10, whereas ghrelin infusion in a model of chronic elevation of serum gonadotropin levels (the transgenic growth retarded male rat) evoked a significant reduction of LH concentrations. Altogether our present results further substantiate the inhibitory effect of ghrelin on basal and stimulated LH secretion in a wide array of experimental conditions. Moreover, our data are the first to demonstrate the ability of UAG, originally considered an inert form of the molecule, to mimic the actions of acylated ghrelin on LH release. These observations reinforce the contention that ghrelin, as putative signal for energy insufficiency, may operate as negative modifier of male puberty and LH secretion, an effect that might be, at least partially, conducted through a GH secretagogue receptor type 1a-independent mechanism.
Assuntos
Hormônio Luteinizante/metabolismo , Hormônios Peptídicos/farmacologia , Animais , Hormônio Foliculoestimulante/metabolismo , Grelina , Gonadotropinas/metabolismo , Hormônio do Crescimento/metabolismo , Homeostase , Hipotálamo/metabolismo , Kisspeptinas , Ligantes , Masculino , Hormônios Peptídicos/metabolismo , Proteínas/metabolismo , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Fatores de TempoRESUMO
The ability of kisspeptins, ligands of the G protein-coupled receptor 54, to potently elicit LH secretion is now undisputed. Yet, most of the pharmacological characterization of their gonadotropin-releasing effects has been conducted after intracerebral administration. In contrast, the effects of peripheral injection of kisspeptin remains less well defined. In this study, dynamic LH secretory responses to iv administration of kisspeptin-10 in different experimental settings are presented, and compared with those evoked by kisspeptin-52, using a protocol of serial blood sampling in conscious, freely moving male rats. LH responsiveness to peripheral administration of kisspeptin appeared extremely sensitive, as doses as low as 0.3 nmol/kg (0.1 microg/rat) evoked robust LH bursts, the magnitude of which was dose-dependent and apparently maximal in response to 3.0 and 30 nmol/kg kisspeptin-10. The ability of kisspeptin-10 to stimulate LH release was fully preserved, and even doubled in terms of relative increases, after short-term fasting despite suppression of prevailing LH levels. Repeated injections of kisspeptin-10 (four boluses, at 75-min intervals) evoked associated LH secretory pulses, the magnitude of which remained constant along the study period. Moreover, in this setting, in vivo LH responses to a terminal injection of GnRH were preserved, whereas basal and depolarization-induced GnRH release ex vivo was significantly enhanced. Finally, iv administration of kisspeptin-52 elicited dynamic LH responses analogous to that of kisspeptin-10; yet, their net magnitude and duration was slightly greater. In summary, we present in this study a series of experiments on the effects of systemic (iv) injection of single or repeated doses of kisspeptin upon dynamic LH secretion in conscious male rats. Aside from potential physiologic relevance, our present data might contribute to setting the basis for the rational therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis.
Assuntos
Hormônio Luteinizante/metabolismo , Oligopeptídeos/farmacologia , Animais , Hormônio Liberador de Gonadotropina/metabolismo , Injeções Intravenosas , Kisspeptinas , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
Loss-of-function mutations of the gene encoding GPR54, the putative receptor for the KiSS-1-derived peptide metastin, have been recently associated with hypogonadotropic hypogonadism, in both rodents and humans. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored. To initiate such analysis, the effects of KiSS-1 peptide on LH secretion were monitored using in vivo and in vitro settings under different experimental conditions. Central intracerebroventricular administration of KiSS-1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KiSS-1 appeared to be mediated via the hypothalamic LHRH. However, no effect of central administration of KiSS-1 was detected on relative LHRH mRNA levels. Likewise, systemic (i.p. and i.v.) injection of KiSS-1 markedly stimulated LH secretion. This effect was similar in terms of maximum response to that of central administration of KiSS-1 and might be partially attributed to its ability to stimulate LH secretion directly at the pituitary. Finally, the LH-releasing activity of KiSS-1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant neurotransmitters in the neuroendocrine control of LH secretion. In summary, our results provide solid evidence for a potent stimulatory effect of KiSS-1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further document a novel role of the KiSS-1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion.
Assuntos
Hormônio Luteinizante/metabolismo , Proteínas/farmacologia , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Aminoácidos Excitatórios/metabolismo , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Intraventriculares , Kisspeptinas , Ligantes , Camundongos , Óxido Nítrico/metabolismo , Hipófise/efeitos dos fármacos , Proteínas/administração & dosagem , Proteínas/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G , Receptores de Kisspeptina-1 , Receptores de Neuropeptídeos/metabolismoRESUMO
Ghrelin, the endogenous ligand of the GH secretagogue receptor, has been recently involved in a wide array of biological functions, including signaling of energy insufficiency and energy homeostasis. On the basis of the proven reproductive effects of other regulators of energy balance, such as the adipocyte-derived hormone leptin, we hypothesized that systemic ghrelin may participate in the control of key aspects of reproductive function. To test this hypothesis, the effects of daily treatment with ghrelin were assessed in rats, pair-fed with control animals, in two relevant reproductive states, puberty and gestation, which are highly dependent on proper energy stores. Daily sc injection of ghrelin (0.5 nmol/12 h; between postnatal d 33 and 43) significantly decreased serum LH and testosterone levels and partially prevented balano-preputial separation (as an external index of puberty onset) in pubertal male rats. On the contrary, chronic administration of ghrelin to prepubertal females, between postnatal d 23 and 33, failed to induce major changes in serum levels of gonadotropins and estradiol, nor did it modify the timing of puberty, as estimated by the ages at vaginal opening and first estrus. Moreover, females treated with ghrelin at puberty subsequently displayed normal estrous cyclicity and were fertile. Conversely, ghrelin administration (0.5 nmol/12 h) during the first half of pregnancy (d 1-11) resulted in a significant decrease in pregnancy outcome, as estimated by the number of pups born per litter, without changes in the number of successful pregnancies at term or gestational length. Overall, our data indicate that persistently elevated ghrelin levels, as a putative signal for energy insufficiency, may operate as a negative modifier of key reproductive states, such as pregnancy and (male) puberty onset.
Assuntos
Hormônios Peptídicos/sangue , Resultado da Gravidez , Prenhez/sangue , Maturidade Sexual , Animais , Esquema de Medicação , Feminino , Grelina , Injeções Subcutâneas , Masculino , Hormônios Peptídicos/administração & dosagem , Hormônios Peptídicos/farmacologia , Gravidez , Ratos , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Fatores de TempoRESUMO
Activation of the gonadotropic axis critically depends on sufficient body energy stores, and conditions of negative energy balance result in lack of puberty onset and reproductive failure. Recently, KiSS-1 gene-derived kisspeptin, signaling through the G protein-coupled receptor 54 (GPR54), has been proven as a pivotal regulator in the control of gonadotropin secretion and puberty. However, the impact of body energy status upon hypothalamic expression and function of this system remains unexplored. In this work, we evaluated the expression of KiSS-1 and GPR54 genes at the hypothalamus as well as the ability of kisspeptin-10 to elicit GnRH and LH secretion in prepubertal rats under short-term fasting. In addition, we monitored the actions of kisspeptin on food intake and the effects of its chronic administration upon puberty onset in undernutrition. Food deprivation induced a concomitant decrease in hypothalamic KiSS-1 and increase in GPR54 mRNA levels in prepubertal rats. In addition, LH responses to kisspeptin in vivo were enhanced, and its GnRH secretagogue action in vitro was sensitized, under fasting conditions. Central kisspeptin administration failed to change food intake patterns in animals fed ad libitum or after a 12-h fast. However, chronic treatment with kisspeptin was able to restore vaginal opening (in approximately 60%) and to elicit gonadotropin and estrogen responses in a model of undernutrition. In summary, our data are the first to show an interaction between energy status and the hypothalamic KiSS-1 system, which may constitute a target for disruption (and eventual therapeutic intervention) of pubertal development in conditions of negative energy balance.
Assuntos
Hipotálamo/fisiologia , Desnutrição/fisiopatologia , Proteínas/genética , Proteínas/metabolismo , Animais , Ingestão de Alimentos/fisiologia , Feminino , Privação de Alimentos/fisiologia , Expressão Gênica , Kisspeptinas , Masculino , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G , Receptores de Kisspeptina-1 , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Índice de Gravidade de Doença , Maturidade Sexual/fisiologiaRESUMO
KiSS-1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, namely kisspeptins, which acting through the G protein-coupled receptor GPR54 are able to inhibit tumor progression. Unexpectedly, a reproductive facet of this newly discovered system has recently arisen, and characterization of the role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion has been initiated. However, such studies have been so far mostly restricted to LH, and very little is known about the actual contribution of this system in the regulation of FSH release. To address this issue, the effects of KiSS-1 peptide on FSH secretion were monitored in vivo and in vitro under different experimental conditions. Intracerebroventricular administration of KiSS-1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED(50) value for the FSH-releasing effects of KiSS-1 of 400 pmol, i.e. approximately 100-fold higher than that of LH. In addition, systemic (ip and iv) injection of KiSS-1 significantly stimulated FSH secretion in vivo. However, KiSS-1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, mechanistic studies revealed that the ability of KiSS-1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e. relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, our results extend previous recent observations on the role of KiSS-1 in the control of LH secretion and provide solid evidence for a stimulatory effect of KiSS-1 on FSH release, acting at central level. Overall, it is proposed that the KiSS-1/GPR54 system is a novel, pivotal downstream element in the neuroendocrine network governing gonadotropin secretion.
Assuntos
Hormônio Foliculoestimulante/metabolismo , Proteínas/farmacologia , Receptores de Neuropeptídeos/fisiologia , Animais , Aminoácidos Excitatórios/farmacologia , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Kisspeptinas , Hormônio Luteinizante/metabolismo , Masculino , Óxido Nítrico/fisiologia , Radioimunoensaio , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G , Receptores de Kisspeptina-1RESUMO
Peroxisome proliferator activated-receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily and, in addition to its relation with obesity and insulin sensitivity, it has recently been localized in human and mice pituitary, indicating a functional significance of PPARgamma in adenopituitary tumours. In the present study, we localized the PPARgamma mRNA and protein in different cell types of rat pituitary. Moreover, using the real-time polymerase chain reaction, we assessed the mRNA expression of PPARgamma in different physiological and pathological settings known to be associated with alterations in anterior pituitary cell proliferation and/or function. Our experiments have shown that PPARgamma mRNA levels were repressed by oestrogen through an oestrogen receptor-alpha effect. However, PPARgamma protein levels were only modified in males but not in females. On the other hand, PPARgamma mRNA expression was increased in dwarf rats in comparison with Lewis rats. Finally, nutritional, thyroid status or pregnancy did not change PPARgamma expression. Taken together, we provide new data regarding the regulation of pituitary PPARgamma mRNA by hormonal and metabolic status.
Assuntos
Nanismo Hipofisário/metabolismo , Estrogênios/fisiologia , Hormônio do Crescimento/fisiologia , PPAR gama/metabolismo , Adeno-Hipófise/metabolismo , Animais , Modelos Animais de Doenças , Receptor alfa de Estrogênio/metabolismo , Feminino , Hormônio do Crescimento/deficiência , Masculino , PPAR gama/genética , Gravidez , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Ratos Sprague-Dawley , Ratos Zucker , Fatores Sexuais , Especificidade da Espécie , Hormônios Tireóideos/metabolismoRESUMO
Ghrelin is a growth hormone-releasing acylated peptide from stomach. The purified peptide consist of 28 amino acids in which the serine 3 residue is n-octanoylated. Ghrelin has been reported to increase in vitro GH secretion as well as in vivo plasma GH levels in pentobarbital anaesthetized rats. The aim of this work was to characterize the stimulatory effect of Ghrelin on in vivo GH secretion in freely-moving rats. Furthermore, we compare the effect of Ghrelin with GHRH. In addition to vehicle, we administered different doses of Ghrelin (3 nmol/Kg, 12 nmol/Kg and 60 nmol/Kg); GHRH (3 nmol/Kg and 12 nmol/kg). Plasma GH levels were measured in blood samples taken at 5, 10, 15, 20, 30 and 45 min after their administration as an i.v. bolus at 0 min. Administration of Ghrelin led to an increase in plasma GH levels at all time-points tested (5, 10, 15, 20 and 30 min, P<0.01; and 45 min, P<0.05) in comparison to control untreated rats. A maximal stimulatory effect on plasma GH was observed following administration of 12 nmol/Kg of Ghrelin, the effect being similar to the one obtained with 60 nmol/Kg in terms of both AUC and mean peak GH levels. At the dose of 3 nmol/Kg GHRH and Ghrelin exhibited a similar stimulatory effect in term of both, AUC and mean peak GH levels. However following administration of a dose of 12 nmol/Kg, the effect of Ghrelin was much greater than the same dose of GHRH in terms of both AUC and mean peak GH levels. In summary, this study provides the first evidences that Ghrelin exert a marked stimulatory effect in plasma GH levels in freely-moving rats and provides further evidences that Ghrelin may play an important role in the physiological control of GH secretion.
Assuntos
Hormônio do Crescimento/metabolismo , Hormônios Peptídicos , Peptídeos/farmacologia , Animais , Área Sob a Curva , Grelina , Hormônio do Crescimento/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Estimulação QuímicaRESUMO
OBJECTIVE: To assess whether some of the alterations in energy homeostasis present in thyroid function disorders and GH deficiency could be mediated by ghrelin. DESIGN: To assess the influence of thyroid status on ghrelin, adult male Sprague-Dawley rats were treated with vehicle (euthyroid), amino-triazole (hypothyroid) or l-thyroxine (hyperthyroid). The influence of GH on ghrelin was assessed in wild-type (control) and GH-deficient (dwarf) Lewis rats. Evaluation of gastric ghrelin mRNA expression in the stomach was carried out by Northern blot. Circulating levels of ghrelin were measured by radioimmunoassay. RESULTS: Hypothyroidism resulted in an increase in gastric ghrelin mRNA levels (euthyroid: 100+/-3.2% vs hypothyroid: 127.3+/-6.5%; P<0.01), being decreased in hyperthyroid rats (70+/-5.4%; P<0.01). In keeping with these results, circulating plasma ghrelin levels were increased in hypothyroid (euthyroid: 124+/-11 pg/ml vs hypothyroid: 262+/-39 pg/ml; P<0.01) and decreased in hyperthyroid rats (75+/-6 pg/ml; P<0.01). Using an experimental model of GH deficiency, namely the dwarf rat, we found a decrease in gastric ghrelin mRNA levels (controls: 100+/-6% vs dwarf: 66+/-5.5%; P<0.01) and circulating plasma ghrelin levels (controls: 124+/-12 pg/ml vs dwarf: 81+/-7 pg/ml; P<0.01). CONCLUSION: This study provides the first evidence that ghrelin gene expression is influenced by thyroid hormones and GH status and provides further evidence that ghrelin may play an important role in the alteration of energy homeostasis and body weight present in these pathophysiological states.
Assuntos
Hormônio do Crescimento/deficiência , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Hormônios Peptídicos , Peptídeos/sangue , Glândula Tireoide/fisiologia , Animais , Metabolismo Energético/fisiologia , Expressão Gênica/fisiologia , Grelina , Masculino , Peptídeos/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND/AIMS: Orexins (OXs) are a newly described family of hypothalamic neuropeptides. Based on the distribution of OX neurons and their receptors in the brain, it has been postulated that they could play a role in the regulation of neuroendocrine function. GH secretion is markedly influenced by nutritional status and body weight. To investigate the role OX-A plays in the neuroregulation of GH secretion we have studied its effect on spontaneous GH secretion as well as GH responses to GHRH and ghrelin in freely moving rats. Finally, we also assessed the effect of OX-A on in vitro GH secretion. METHODS: We administered OX-A (10 microg, i.c.v.) or vehicle (10 microl, i.c.v.) to freely moving rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. RESULTS: Administration of OX-A led to a decrease in spontaneous GH secretion in comparison with vehicle-treated rats, as assessed by mean GH levels (means+/-s.e.m. 4.2+/-1.7 ng/ml vs 9.4+/-2.2 ng/ml; P<0.05), mean GH amplitude (3.6+/-0.5 ng/ml vs 20.8+/-5.6 ng/ml; P<0.01) and area under the curve (848+/-379 ng/ml per 4 h vs 1957+/-458 ng/ml per 4 h; P<0.05). In contrast, OX-A failed to modify in vivo GH responses to GHRH (10 microg/kg, i.v.) although it markedly blunted GH responses to ghrelin (40 microg/kg, i.v.) (mean peak GH levels: 331+/-71 ng/ml, vehicle, vs 43+/-11 ng/ml in OX-A-treated rats; P<0.01). Finally, OX-A infusion (10(-7), 10(-8) or 10(-9) M) failed to modify in vitro basal GH secretion or GH responses to GHRH, ghrelin and KCl. CONCLUSIONS: These data indicate that OX-A plays an inhibitory role in GH secretion and may act as a bridge among the regulatory signals that are involved in the control of growth, nutritional status and sleep regulation.
Assuntos
Proteínas de Transporte/farmacologia , Hormônio do Crescimento/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular , Neuropeptídeos/farmacologia , Ciclos de Atividade , Animais , Área Sob a Curva , Grelina , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Masculino , Orexinas , Hormônios Peptídicos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Leptin, the product of the ob gene, is a hormone secreted by adipocytes that regulates food intake and energy expenditure. The hypothalamus-pituitary-thyroid axis is markedly influenced by the metabolic status, being suppressed during food deprivation. The aim of the present study was to assess whether leptin can act as a metabolic signal connecting the adipose tissue with the pituitary-thyroid axis. We studied the effect of leptin administration (10 microg, i.c.v.) on spontaneous TSH secretion and TSH responses to TRH in euthyroid and hypothyroid food-deprived rats. Spontaneous TSH secretion was assessed over 6 h with samples taken every 7 min. Administration of leptin to food-deprived euthyroid rats led to a reversal of the inhibitory effect exerted by fasting on spontaneous TSH secretion. This stimulatory effect of leptin on spontaneous TSH appears to be dependent on the thyroid status since it could not be observed in hypothyroid rats. This data suggests that blunted spontaneous TSH secretion in food-deprived rats is a functional and reversible state, and that the decreased leptin concentrations could be the primary event responsible for the suppression of the hypothalamic-pituitary-thyroid-axis in food-deprived rats.
Assuntos
Leptina/metabolismo , Tireotropina/metabolismo , Animais , Feminino , Privação de Alimentos , Ratos , Ratos Sprague-Dawley , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/metabolismoRESUMO
Rheumatic fever is the most common cause of acquired heart disease in children and young adults worldwide, mainly in developing countries, and is the reason that a large number of patients with mitral stenosis will require some modality of treatment during their life span. The early therapeutic approach for this condition was solely surgical, but since the early 1960s, several balloon catheter interventional techniques have emerged as alternatives to surgical treatment. In 1976 Inoue described a novel single-balloon device designed specifically for percutaneous transvenous mitral commissurotomy (PMC), and in 1982 the first clinical application of Inoue's technique was successfully accomplished. Ever since several clinical trials established PMC as an effective and safe procedure for severe mitral stenosis in more than 30,000 patients worldwide, percutaneous balloon techniques have been considered the method of choice in selected patients (functional class >II, mitral valve area <1.5 cm2, and Wilkins' score <8) for several reasons. PMC is a nonsurgical method with results similar to those of surgical intervention, but without the unnecessary risks and complications of general anesthesia and extracorporeal circulation pump. Both PMC and surgical commissurotomy yield comparable acute and long-term results and similar restenosis rates. Moreover, PMC is the strategy of choice in symptomatic pregnant women with mitral stenosis, as well as in some cases with restenosis after a previous PMC. Patient selection and procedural technique are reviewed in detail.
Assuntos
Cateterismo/instrumentação , Estenose da Valva Mitral/terapia , Cardiopatia Reumática/terapia , Adolescente , Adulto , Criança , Ensaios Clínicos como Assunto , Contraindicações , Desenho de Equipamento , Feminino , Humanos , Masculino , Seleção de Pacientes , Gravidez , Resultado do TratamentoRESUMO
The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several studies have demonstrated the role of this subfamily on glucose metabolism, insulin sensitivity and energy balance. These studies have focused mainly in liver and skeletal muscle. However, its potential role in white adipose tissue (WAT), one of the most important tissues involved in the regulation of energy homeostasis, is not well-studied. The aim of this work was to elucidate the regulation of NR4A in WAT under different physiological and pathophysiological settings involved in energy balance such as fasting, postnatal development, gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since the expression of the 3 isoforms is increased after fasting in a leptin-independent manner and sex steroid hormones also modulate NR4A expression in males and females. Our findings indicate that NR4A are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status.
Assuntos
Tecido Adiposo Branco/metabolismo , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Tecido Adiposo Branco/patologia , Animais , Restrição Calórica , Proteínas de Ligação a DNA/metabolismo , Metabolismo Energético , Jejum , Feminino , Glucose/metabolismo , Hormônios Esteroides Gonadais/genética , Hormônios Esteroides Gonadais/metabolismo , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/genética , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Injeções Intraventriculares , Leptina/administração & dosagem , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Orquiectomia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais , Transdução de SinaisRESUMO
Resumen OBJETIVO: exponer el caso clínico de una paciente con fístula arteriovenosa uterina secundaria a legrado instrumentado, asociada con pólipos placentarios. CASO CLÍNICO: paciente de 29 años de edad, que acudió a consulta médica por deseo de embarazo, obtenido de manera espontánea, que finalizó en aborto por embarazo anembriónico de 8 semanas. El médico tratante efectuó legrado uterino instrumentado. Cinco meses después del evento, la paciente tuvo sangrado uterino anormal (abundante), que requirió hospitalización. El ultrasonido reportó útero con aumento de vascularización en la pared posterior, con sospecha de fístulas arteriovenosas, velocimetría Doppler normal y diástole alta de baja resistencia. El médico le sugirió embolización arterial selectiva. Una vez valorada por el equipo médico, se efectuó la evaluación integral de la patología uterina mediante ultrasonido, en el que se observó una masa intracavitaria con ecos mixtos, sugerentes de retención de restos ovuloplacentarios, comprobados posteriormente con histeroscopia. Durante el procedimiento histeroscópico (efectuado con histeroscopio Hopkins II Karl Storz de 2 mm y "camisa" diagnóstica de 2.8 mm de grosor) se detectó una masa compatible con restos ovuloplacentarios adheridos a la cara posterior del útero. Después de la valoración integral se decidió efectuar la evacuación uterina, por vía histeroscópica, con resectoscopio sin energía. El estudio histopatológico reportó restos ovuloplacentarios con marcados cambios por retención, decidua necrótica y hemorrágica, con inflamación subaguda severa. La paciente evolucionó satisfactoriamente durante el periodo posquirúrgico. La evaluación ultrasonográfica de control no mostró la fístula arteriovenosa uterina (desapareció la imagen en "ovillo").
Abstract OBJECTIVE: We report a case of a patient with arteriovenous fistula secondary to an instrumented uterine curettage, related to presence of placental polyps. CLINICAL CASE: A 29-year-old woman, who went to a doctor's office for a pregnancy protocol, reached spontaneously, but its finalized in abortion for an anembrionrary pregnancy of 8 weeks. The Doctor performed instrumented uterine curettage. Five months after the event, the patient had abnormal (abundant) uterine bleeding, which required hospitalization. Ultrasound with increased vascularization in the posterior wall, with suspected venereal arteries, normal Doppler velocimetry, and low diastole with low resistance. The physician suggested selective arterial embolization. A comprehensive evaluation of the pathology was performed by ultrasound, in which an intracavitary mass was observed with mixed echoes, suggestions of retention of ovuloplacental remains, later verified with hysteroscopy. During the hysteroscopic procedure (with Hopkins II, Karl Storz of 2 mm and a 2.8 mm "diagnostic" shirt), a mass compatible with the ovuloplacental remains attached to the posterior aspect of the uterus was detected. After the integral evaluation, it was decided to perform the uterine evacuation, using hysteroscopy, with a resectoscope without energy. The histopathological study reported ovuloplacental remains with marked changes by retention, necrotic and hemorrhagic decidua, with severe subacute inflammation. The patient progressed satisfactorily during the postoperative period. The ultrasonographic evaluation of control did not show the arteriovenous fistula.
RESUMO
La disrupción del tallo hipofisario es una patología infrecuente que causa hipogenesia de la pituitaria anterior y agenesia o ectopia \r\nde la hipófisis posterior. El diagnóstico se realiza tardíamente cuando aparecen mayores alteraciones antropométricas o disminu\r\n-\r\nciones en la velocidad de crecimiento. Se estima que solo el 23% de los casos se diagnostica en el periodo neonatal, con lo cual \r\nse logra disminuir la mortalidad y morbilidades secundarias. Este estudio describe el caso de un recién nacido con hipoglicemia \r\npersistente desde el nacimiento, micropene e incisivo único central. Se solicitó resonancia magnética cerebral y determinación \r\nsérica hormonal para confirmar el diagnóstico de panhipopituitarismo congénito secundario a la disrupción del tallo hipofisario. \r\nSe inició el reemplazo hormonal de forma temprana.
The disruption of the pituitary stalk is a rare disease that causes \r\nhypogenesis of the anterior pituitary and agenesis or ectopic \r\nposterior hypophysis. The diagnostic is carried out late, when \r\ngreater anthropometric alterations or decreases in the growth \r\nspeed materialize. Only 23% of the cases are diagnosed during \r\nthe neonatal period, therefore decreased in mortality and \r\nsecondary morbidities is achieved. This study describes the \r\ncase of a newborn that had persistent hypoglycemia from \r\nbirth, micropenis, and a single central incisor. A brain magnetic \r\nresonance and determination of serum hormones were \r\nrequested to confirm the diagnostic of congenital panhypo\r\n-\r\npituitarism secondary to the disruption of the pituitary stalk. \r\nHormone replacement was initiated early.
A interrupção da haste hipofisária é uma patologia pouco \r\nfrequente que causa hipogenesia da pituitária anterior e \r\nagenesia, ou ectopia, da hipófise posterior. O diagnóstico é \r\nrealizado tardiamente quando aparecem maiores alterações \r\nantropométricas ou diminuições na velocidade do crescimento. \r\nEstima-se que apenas 23% dos casos são diagnosticados no \r\nperíodo neonatal, com o que se atinge redução da morta\r\n-\r\nlidade e morbidades secundárias. Este estudo descreve o \r\ncaso de um recém-nascido com hipoglicemia persistente \r\ndesde o nascimento, micro pênis e incisivo central único. Foi \r\nsolicitada ressonância magnética cerebral e determinação \r\nsérica hormonal para confirmar o diagnóstico de pan-hipo\r\n-\r\npituitarismo congênito secundário na interrupção da haste \r\nhipofisária. A reposição hormonal foi iniciada precocemente.
Assuntos
Recém-Nascido , Hormônio do Crescimento , Crescimento , Hipoglicemia , HipopituitarismoRESUMO
Este es un estudio cualitativo de tipo fenomenológico para determinar las percepciones sobre la lactancia humana en \r\nmujeres gestantes que asisten al Hospital San Martín de Porres en Chocontá (Cundinamarca). Algunas han experi\r\n-\r\nmentado esta práctica y otras son primigestantes y nunca lo han hecho. La población fue seleccionada por efecto de \r\nbola de nieve y la muestra por medio del efecto de saturación. Se realizó una entrevista estructurada a los dos grupos. \r\nLos datos se analizaron definiendo categorías y codificando las respuestas y hallazgos.\r\nLa asistencia juiciosa de estas mujeres embarazadas a sus controles prenatales y cursos psicoprofilácticos incide en \r\nla decisión y motivaciones para la lactancia humana de manera positiva. Se concluye que la implementación de polí\r\n-\r\nticas hospitalarias permite que los profesionales de salud y otros agentes comunitarios emitan conocimientos claros y \r\nsencillos acerca de la lactancia para las familias gestantes con el fin de garantizar como mínimo la lactancia humana \r\nexclusiva durante los seis primeros meses de vida.
This paper present a phenomenological qualitative study \r\nto determine the perceptions of human breastfeeding \r\nin women who have breastfed, those who are pregnant \r\nfor the first time, and those who have not breastfed, in \r\nHospital San Martín de Porres in Chocontá, using a \r\nstructured interview. The population was selected by \r\nsnowball effect and the sample was defined by means of \r\nsaturation effect. The data analysis was performed to the \r\ntwo groups defining categories, coding the responses and \r\nfindings, allowing the approximation to the experiences \r\nof the women interviewed.\r\nRegular prenatal checkups and courses positively impact \r\nthe decision and motivations for human breastfeeding, \r\nindicating that a hospital's policy implementation helps \r\nhealth professionals and other community agents convey \r\nclear and simple concepts about breastfeeding to expec\r\n-\r\ntant families, in order to ensure only human breastfeeding \r\nfor at least the first 6 months of life.
Este artigo apresenta um estudo qualitativo fenomeno\r\n-\r\nlógico para determinar as percepções de amamentação \r\nem mulheres, no hospital em San Martin de Porres \r\nEm Chocontá através de entrevista estruturada, que se \r\nsubmeteram a esta prática e aquelas que estão grávidas \r\npela primeira vez. A população foi selecionada por efeito \r\nde bola de neve e a amostra introduzida por efeito de \r\nsaturação. A análise dos dados foi realizada sobre os \r\ndois grupos determinando categorias, codificação das \r\nrespostas e resultados, permitindo a aproximação das \r\nexperiências das mulheres entrevistadas.\r\nConsultas pré-natais dessas mulheres grávidas impactam \r\npositivamente a decisão e as razões para participar em \r\namamentação concluiu que a implementação de políticas \r\ndos hospital ajudam os profissionais e outros agentes \r\ncomunitários emitem conhecimento claro e simples sobre \r\na amamentação para as mulheres grávidas, a fim de \r\ngarantir o aleitamento materno a mínimo dos primeiros \r\nseis meses de vida.