RESUMEN
While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.
Asunto(s)
Leptina , Progesterona , Ratas , Animales , Femenino , Leptina/metabolismo , Progesterona/farmacología , Progesterona/metabolismo , Ingestión de Alimentos , Peso Corporal , Hipotálamo , Proteínas Portadoras , Estrógenos/farmacología , Estrógenos/metabolismo , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Proopiomelanocortina/farmacologíaRESUMEN
OBJECTIVE: Estrogen plays an important role in feeding and energy balance, and the critical role of estrogen in the control of appetite and energy balance is mediated by hypothalamic estrogen receptor (ER) alpha. In undernourished rodents, hypothalamic ER alpha mRNA expression are decreased. Responses of some hypothalamic factors to negative energy balance develop during the early neonatal period. DESIGN: In this study, we examined the developmental changes of fasting-induced alterations in hypothalamic ER alpha mRNA expression in female rats. RESULTS: ER alpha mRNA expression was reduced after a 12-h or 24-h fast at postnatal days 15 and 25, but not at day 5. Serum estradiol levels in postnatal day 25 rats were not changed by fasting. Although serum leptin levels were suppressed by fasting at all ages, hypothalamic ER alpha mRNA expression at postnatal day 25 was not changed by leptin administration after a 24-h fast. CONCLUSIONS: These data show that the sensitivity of hypothalamic ER alpha to negative energy balance may not be established in the early neonatal period, and that it develops by postnatal day 15. Decreased leptin levels might not be involved in the alterations of hypothalamic ER alpha mRNA expression in the undernourished condition.
Asunto(s)
Metabolismo Energético/fisiología , Receptor alfa de Estrógeno/sangre , Receptor alfa de Estrógeno/genética , Privación de Alimentos/fisiología , Hipotálamo/crecimiento & desarrollo , Hipotálamo/fisiología , Factores de Edad , Animales , Animales Recién Nacidos , Peso Corporal/fisiología , Femenino , Leptina/sangre , Leptina/farmacología , Embarazo , ARN Mensajero/metabolismo , RatasRESUMEN
Secretion of glucocorticoids is widely known as a key endocrine response to stresses. Prenatal dexamethasone administration induces intrauterine growth retardation and delayed onset of puberty in female rats independent of the hypothalamic Kiss1-gonadotropin-releasing hormone (GnRH) system. The aim of this study was to evaluate the influence of chronic intracerebroventricular (central, CD) or subcutaneous (peripheral, PD) dexamethasone administration to prepubertal female rats on the onset of puberty and body weight change. Rats administered dexamethasone from day 25 to day 34 (CD and PD) showed significantly reduced body weight gain throughout the experimental period and delayed onset of vaginal opening compared with rats administered saline centrally (CS) or peripherally (PS). At 34 days old, hypothalamic Kiss1r mRNA levels were significantly lower with CD than with CS. No significant differences were seen between rats administered saline and rats administered dexamethasone with regard to hypothalamic Kiss1, GnRH and NPY mRNA levels or serum LH levels. Serum leptin concentrations were higher in CD and PD than in the controls (CS and PS). These results suggest that the delayed onset of puberty induced by prepubertal dexamethasone administration occurs independent of the hypothalamic Kiss1-GnRH system.
Asunto(s)
Glucocorticoides/farmacología , Hormona Liberadora de Gonadotropina/fisiología , Hipotálamo/efectos de los fármacos , Hipotálamo/crecimiento & desarrollo , Kisspeptinas/fisiología , Maduración Sexual/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/fisiología , Femenino , Glucocorticoides/administración & dosificación , Hormona Liberadora de Gonadotropina/genética , Crecimiento/efectos de los fármacos , Hormonas/sangre , Bombas de Infusión , Kisspeptinas/genética , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Vagina/crecimiento & desarrollo , Vagina/fisiologíaRESUMEN
Early-life immune stress may have long-lasting effects, known as programming effects, on the physiological response to stress in adulthood. There may be a critical window after birth during which such a challenge can induce long-lasting alterations. However, there are few reports regarding the consequences of this phenomenon for later reproductive function. Here we report on induction by early-life LPS injection of long-lasting alterations in the adult LH response to homotypic immune stress in male rats. First, we investigated developmental changes in the LH response to LPS, since immune challenge during the stress hyporesponsive period can induce long-lasting effects on physiological functions. Rat serum LH concentrations were decreased by LPS (100 µg/kg) injection on postnatal day 15 or 25, but not day 10, suggesting that the period prior to postnatal day 10 is the stress hyporesponsive period for LH. Serum LH concentrations and body weight were decreased by adult LPS (400 µg/kg) injection in rats given saline or LPS (100 µg/kg) on postnatal day 25, but not in rats given LPS (100 µg/kg) on postnatal day 10. Expression of hypothalamic IL-1ß and TNF-α mRNA, which suppress serum LH during immune stress, were equally increased in these groups by adult LPS (400 µg/kg) injection. The present data suggest that the period prior to postnatal day 10 is the critical window in which immune stress can induce long-lasting alterations in the LH response, but that IL-1ß and TNF-α are not involved in mediating the altered response.
Asunto(s)
Hipotálamo/inmunología , Sistema Inmunológico/fisiología , Hormona Luteinizante/metabolismo , Reproducción , Estrés Fisiológico/inmunología , Animales , Animales Recién Nacidos , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Regulación del Desarrollo de la Expresión Génica/inmunología , Sistema Inmunológico/crecimiento & desarrollo , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Lipopolisacáridos/administración & dosificación , Hormona Luteinizante/sangre , Hormona Luteinizante/genética , Masculino , Neuroinmunomodulación , Ratas , Ratas Sprague-Dawley , Reproducción/inmunología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) is considered to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis. To understand the functional significance of this neuropeptide, we investigated the physiological changes in RFRP at mRNA and peptide levels, as well as at the mRNA level of its cognate receptor, G protein-coupled receptor 147 (GPR147), in the rat hypothalamus during development. We also investigated the effects of gonadal steroids on mRNA expression levels of these molecules. In male rats, mRNA expressions of both RFRP and GPR147 increased from postnatal days 12 and 16, peaking at postnatal days 35 and 42, respectively. However, their expressions fell at postnatal day 49. In female rats, mRNA expression of RFRP continued to increase throughout development; mRNA expression of GPR147 in female rats increased from postnatal day 16, peaking at postnatal day 28, but decreased from postnatal day 35. The hypothalamic contents of RFRP on postnatal days 28 and 42 were significantly higher than on postnatal day 4 in male rats, and those on postnatal day 42 were significantly higher than those on postnatal days 4 and 28 in females. Neither orchidectomy nor ovariectomy influenced mRNA expression levels of RFRP or GPR147 in the prepubertal period when endogenous sex steroid levels were low in males and females. Administration of estradiol-17ß (E2) increased mRNA expression of RFRP in prepubertal females. These results suggest that the hypothalamic RFRP system changes during development. An ovarian sex steroid, E2, may stimulate mRNA expression of RFRP in the prepubertal period when the basal E2 concentration is low.
Asunto(s)
Envejecimiento/fisiología , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Neuropéptidos/metabolismo , Receptores de Neuropéptido/genética , Factores de Edad , Animales , Animales Recién Nacidos , Estradiol/farmacología , Estradiol/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Masculino , Neuropéptidos/genética , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Caracteres Sexuales , Factores de TiempoRESUMEN
Kisspeptin, which is the product of the kiss1 gene and its receptor kiss1r, have emerged as the essential gatekeepers of reproduction. The present study used gonadally intact female rats to evaluate fasting-induced suppression of the KiSS-1 system of anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) under normal physiological conditions. Starting on the day of estrous, one group of rats was subjected to 72 h of food deprivation, while the other group of rats was able to continue feeding ad libitum. The length of the estrous cycle was significantly longer in the food-deprived rats as compared to the feeding rats. At the end of the 72-h food deprivation period, all of the food-deprived rats were at the diestrous phase, with their serum concentrations of LH and leptin significantly lower than that observed in the feeding rats. In addition, as compared to the feeding rats, the expression levels of kiss1 mRNA were significantly lower in the food-deprived rats in the posterior hypothalamic block, which contained the ARC, but not in the anterior hypothalamic block, which contain the AVPV. However, both the kiss1r mRNA expression levels in the anterior and posterior hypothalamic blocks and the neurokinin B and neurokinin 3 receptor mRNA expression levels in the posterior hypothalamic block were not significantly different between the feeding and food-deprived rats. Thus, lower kiss1 mRNA levels in the ARC appear to be responsible for the fasting-induced inhibition of gonadotrophin secretion and subsequent prolongation of the estrous cycle.
Asunto(s)
Privación de Alimentos/fisiología , Hipotálamo/fisiología , Kisspeptinas/metabolismo , ARN Mensajero/metabolismo , Animales , Ciclo Estral/fisiología , Femenino , Hipotálamo/metabolismo , Kisspeptinas/genética , Leptina/sangre , Hormona Luteinizante/sangre , Neuroquinina B/genética , Neuroquinina B/metabolismo , ARN Mensajero/química , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Kisspeptina-1 , Receptores de Neuroquinina-3/genética , Receptores de Neuroquinina-3/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1ß (IL1ß) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1ß mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1ß mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1ß synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency.
Asunto(s)
Peso Corporal/inmunología , Ovariectomía , Ovario/inmunología , Estrés Fisiológico/inmunología , Animales , Peso Corporal/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Humanos , Hipotálamo/inmunología , Hipotálamo/metabolismo , Interleucina-1beta/biosíntesis , Interleucina-1beta/inmunología , Leptina/sangre , Leptina/inmunología , Lipopolisacáridos/farmacología , Menopausia/sangre , Menopausia/inmunología , Modelos Biológicos , Ovario/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/inmunología , Ratas , Ratas Sprague-DawleyRESUMEN
In addition to its role as a regulator of energy homeostasis, leptin plays a pivotal role in some immune/inflammatory responses. Synthesis and secretion of leptin are increased under immune stress conditions, and increased leptin may participate in the development of anorexia and fever. These actions are partially mediated by up-regulation of hypothalamic IL-1ß. Leptin also protects against immune stress-induced lethality. On the other hand, the response and roles of leptin to immune stress conditions in the neonatal period have scarcely been examined. We hypothesized that 1. the response of leptin to immune stress would be suppressed in the early neonatal period, 2. hyporesponse of leptin in the early neonatal period would attenuate the anorectic response and increase the lethal rate under immune stress conditions and 3. supplementation of leptin in the early neonatal period would increase the anorectic response, whereas it would decrease the lethal rate under immune stress conditions. To test these hypotheses, we first examined the developmental changes in the responses of leptin and hypothalamic proinflammatory cytokines, i.e., IL-1ß and TNF-α, to LPS-induced immune stress in female rats. We also examined the developmental changes in the anorectic response and lethality rate under LPS-induced immune stress conditions. Five- and 15-day-old rats showed no leptin response and a weak hypothalamic IL-1ß response to LPS when compared with 25- and 42-day-old rats. Fifteen-day-old rats showed low anorectic responses and high lethality rates when compared with 25- and 42-day-old rats under LPS-induced immune stress conditions. We then examined whether administration of leptin affected the response to the anorectic and lethal effects of LPS in 15-day-old rats. Administration of leptin further attenuated body weight after LPS injection, but not after saline injection. On the other hand, administration of leptin did not affect survival rate. In addition, hypothalamic IL-1ß mRNA levels were not affected by leptin administration. In conclusion, the absence of a leptin response may act to prevent immune stress-induced anorexia during the early neonatal period.
Asunto(s)
Apetito/fisiología , Hipotálamo/metabolismo , Interleucina-1beta/biosíntesis , Leptina/metabolismo , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Animales Recién Nacidos , Apetito/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Femenino , Hipotálamo/efectos de los fármacos , Hipotálamo/crecimiento & desarrollo , Interleucina-1beta/genética , Leptina/administración & dosificación , Leptina/sangre , Embarazo , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Neuropeptide Y (NPY) is an important orexigenic peptide that acts in the brain. The increase in hypothalamic NPY mRNA expression induced by fasting is mainly caused by a decrease in the effects of leptin. We investigated the developmental changes in the sensitivities of leptin and hypothalamic neuropeptide Y to fasting. Hypothalamic NPY mRNA levels were increased by fasting in postnatal days 15 and 25 rats, but not in postnatal day 5 rats. Serum leptin levels were decreased by fasting in rats at all ages (days 5, 15, and 25). In addition, hypothalamic OB-Rb mRNA levels were decreased by fasting in postnatal day 25 rats, but not in postnatal day 5 or 15 rats. Although the percentage of fating-induced decrease in the serum leptin level was larger in the postnatal day 15 rats than in the postnatal day 25 rats, the percentage of increase in the hypothalamic NPY mRNA level in the postnatal day 15 rats was smaller than that in the postnatal day 25 rats. There was a strong inverse correlation between serum leptin levels and hypothalamic NPY mRNA levels in the postnatal day 25 rats, whereas no significant correlation was found between these parameters in the postnatal day 5 or 15 rats. These findings indicate that the sensitivity of hypothalamic NPY mRNA expression to food deprivation and hypoleptinemia has developed by postnatal day 25.
Asunto(s)
Privación de Alimentos/fisiología , Hipotálamo/metabolismo , Leptina/sangre , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , ARN Mensajero/metabolismo , Factores de Edad , Animales , Femenino , Leptina/genética , Privación Materna , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: Reproductive functions are influenced by various feeding regulators. Orexin, which is one of orexinergic peptides, suppresses the pulsatile secretion of luteinizing hormone (LH) in bilaterally ovariectomized (OVX) rats. However, the mechanism of this effect is still not clear. To investigate whether neuropeptide Y (NPY) is involved in the orexin A-mediated suppression of pulsatile LH secretion, we evaluated the effects of NPY antibody on the suppressive effect of orexin A. METHODS: Orexin A was administered intracerebroventricularly (icv) and NPY antibody (NPY-Ab) was injected before icv administration of orexin A in OVX rats. Pulsatile LH secretion was analyzed by measuring serum LH concentrations in the next 2 h in blood samples drawn at 6-min intervals by radioimmunoassay. RESULTS: Administration of orexin A significantly reduced the mean LH concentration and LH pulse frequency. Co-administration of NPY antibody with orexin A significantly restored the suppressive effect of orexin A on the mean LH concentration and LH pulse frequency. CONCLUSION: NPY mediated the suppressive effect of intracerebroventricularly injected orexin A on pulsatile LH secretion, suggesting that hypothalamic orexin suppressed pulsatile gonadotropin-releasing hormone (GnRH) secretion via NPY in the hypothalamus of female rats.
Asunto(s)
Hormona Liberadora de Gonadotropina/metabolismo , Péptidos y Proteínas de Señalización Intracelular/administración & dosificación , Neuropéptido Y/fisiología , Neuropéptidos/administración & dosificación , Animales , Femenino , Hormona Liberadora de Gonadotropina/sangre , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Neuropéptido Y/antagonistas & inhibidores , Orexinas , Ovariectomía , Ratas , Ratas WistarRESUMEN
Intrauterine growth retardation (IUGR) is an important risk factor for the pathogenesis of diseases after birth. Long-lasting alterations in the structure and function of tissues and the neuroendocrine system, which are known as 'programming effects', increase the risks of these diseases. To investigate the pathophysiology of programming effects, several kinds of IUGR rodent models have been used in experiments. Sexual maturation and the onset of puberty are delayed in these models. We have previously reported that decreased action of hypothalamic kisspeptin, which is a positive regulator of GnRH, contributes to the delayed onset of puberty in undernutrition-induced IUGR rats. The aim of this study was to evaluate whether the hypothalamic Kiss1-Kiss1r-GnRH system is also altered in dexamethasone-induced IUGR rats. Compared with offspring from an untreated mother (control), offspring from a dexamethasone administered mother (DEX) showed a significant reduction in body weight throughout the experimental period (from birth to the prepubertal period) and the delayed onset of puberty. There were no significant differences between the control and DEX groups with regard to their hypothalamic Kiss1, Kiss1r, GnRH, CRH, NPY and POMC mRNA levels during the experimental period or their serum LH, FSH, or leptin concentrations at postnatal day 28 or vaginal opening (VO). Compared with the control, DEX showed significantly lower ovarian weight at postnatal day 28, but not at VO. These results suggested that the delayed onset of puberty induced by maternal dexamethasone administration would occur independently of hypothalamic Kiss1-Kiss1r-GnRH system.
Asunto(s)
Glucocorticoides/farmacología , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/efectos de los fármacos , Proteínas/metabolismo , Pubertad Tardía/fisiopatología , Receptores Acoplados a Proteínas G/metabolismo , Animales , Dexametasona/farmacología , Femenino , Retardo del Crecimiento Fetal/fisiopatología , Kisspeptinas , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores de Kisspeptina-1RESUMEN
Decreased activity of kisspeptin, the product of the hypothalamic Kiss1 gene, is the major cause of the suppression of reproductive function in subnutritional conditions. The sensitivities of the endocrine and the hypothalamic neuronal systems to nutritional status develop during the neonatal period. We examined the developmental changes in the sensitivity of hypothalamic mRNA expression of Kiss1 and its receptor, Kiss1r, to nutritional status in female rats. Kiss1 mRNA expression was reduced by 24âh food deprivation (24âh FD) at postnatal day 25, but not at postnatal day 5 or 15. Kiss1r mRNA expression was reduced by the 12 or 24âh FD at postnatal days 5 and 25, but not at postnatal day 15. Kiss1r mRNA level was found to be correlated with the plasma leptin level, and the administration of leptin, which increased the serum leptin concentration above the physiological range, restored the acute FD-induced suppression of Kiss1r mRNA expression. These data suggest that the hypothalamic Kiss1 and Kiss1r mRNA expression is differentially affected by the nutritional condition at different age points. It is speculated that the sensitivity of Kiss1 mRNA, which is expressed in kisspeptin neuron, to nutritional status develops during the neonatal period. On the other hand, it seems that the sensitivity of Kiss1r mRNA, which is expressed in GnRH neuron, to nutritional status has been already established during the early neonatal period. These data also show that hypoleptinemia plays a role in the reduction of hypothalamic Kiss1r mRNA expression under subnutritional conditions.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Estado Nutricional/fisiología , Proteínas/metabolismo , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Femenino , Privación de Alimentos , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas , Leptina/farmacología , Proteínas/genética , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores de Kisspeptina-1RESUMEN
It has been reported that prenatal immune stress induced by lipopolysaccharides or cytokines increases food intake and leads to obesity and other features of metabolic syndrome in adulthood. Using Sprague-Dawley rats, we evaluated whether neonatal LPS injection altered their body weight regulation systems under non-stress and immune stress conditions. On Day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) (PND(10)LPS) or saline (PND(10)Saline). After weaning, body weight was significantly elevated in PND(10)LPS compared with PND(10)Saline. Thereafter, the rats were injected with LPS (100 microg/kg, i.p.) or saline (used as a basal condition) from 7 to 8 weeks of age. Under basal conditions, cumulative food intake were significantly higher, serum leptin concentration was significantly increased, and hypothalamic NPY mRNA expression was significantly decreased in PND(10)LPS compared with PND(10)Saline. Under adult LPS injected conditions, body weight gain and cumulative food intake were suppressed in both the PND(10)LPS and PND(10)Saline groups compared with those observed under basal adult saline-injected conditions. The suppressive effects induced by adult LPS injection were less evident in the PND(10)LPS group than in the PND(10)Saline group. Adult LPS injection increased the serum leptin concentration in the PND(10)Saline rats, but not in the PND(10)LPS rats. In addition, adult LPS injection increased the mRNA expression of anorexinergic factors (IL-1beta, and TNF-alpha), and decreased that of the orexinergic factor NPY in both groups. However, the influence of adult LPS injection upon these factors was less evident in the PND(10)LPS group than in the PND(10)Saline group. These results suggest that neonatal LPS injection alters body weight regulation under both non-stress and immune stress conditions in male rats. Changes in the endocrine, neuropeptide, and cytokine regulation systems might be involved in these alterations.
Asunto(s)
Peso Corporal/inmunología , Peso Corporal/fisiología , Lipopolisacáridos/toxicidad , Envejecimiento , Animales , Animales Recién Nacidos , Corticosterona/sangre , Conducta Alimentaria/fisiología , Hipotálamo/metabolismo , Interleucina-1beta/metabolismo , Leptina/sangre , Masculino , Neuropéptido Y/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Neonatal immune challenges have a long-lasting influence on immune response. Using male Sprague-Dawley rats, we examined whether neonatal lipopolysaccharide (LPS) challenge alters the sensitivity of male reproductive function to adult LPS challenge and at which level (central or testes) the alteration occurs. We also examined the mRNA expression of proinflammatory cytokines in the hypothalamus and testes because they have a pivotal role in immune stress-induced suppression of gonadotropin secretion and testosterone synthesis. On day 10 after birth, all the pups were injected with LPS (100 microg/kg, i.p.) or saline. Thereafter, LPS (100 microg/kg, i.p.) or saline was injected in adulthood at 8 weeks of age. The serum LH concentration was decreased by LPS injection during adulthood in the neonatal saline-injected rats. This suppressive effect was not seen in the neonatal LPS-injected rats. The serum testosterone concentration was decreased by adult LPS injection in both the neonatal LPS-injected and neonatal saline-injected rats. The expression levels of KiSS-1, which encodes kisspeptin, known to have a crucial role in the regulation of gonadotropin secretion, and GnRH mRNA in the hypothalamus and LHbeta mRNA in the pituitary were not influenced by neonatal or adult LPS injection. On the other hand, the expression levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA in the hypothalamus and testes were increased by adult LPS injection in both the neonatal LPS-injected and neonatal saline-injected rats. Furthermore, the expression levels of these factors in the hypothalamus after adult LPS injection were significantly lower in the neonatal LPS-injected rats than in the neonatal saline-injected rats. These findings indicate that neonatal LPS challenge reduces the sensitivity of male reproductive function to the suppressive effects of LPS, mainly at the central level. Attenuation of proinflammatory cytokine synthesis in the hypothalamus might be involved in this alteration.
Asunto(s)
Animales Recién Nacidos , Lipopolisacáridos/farmacología , Hormona Luteinizante/metabolismo , Estrés Fisiológico/efectos de los fármacos , Animales , Femenino , Hipotálamo/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Hormona Luteinizante/sangre , Masculino , Hipófisis/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Testículo/metabolismo , Testosterona/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A single immune challenge with lipopolysaccharide (LPS) in the neonatal period has a long-lasting influence on immune response. Using female Sprague-Dawley rats, we examined whether neonatal LPS challenge influences the life-long neuroendocrine sensitivity of reproductive function and feeding behavior to LPS, and whether stress-related neuropeptides and their receptors are involved in neonatal LPS-induced physiological change. On day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) or saline. Then, in Experiment 1, LPS (100 microg/kg, i.p.) or saline was injected at diestrous in adulthood, and the length of the estrous cycle, 24h food intake and body weight change were recorded. In Experiment 2, the mRNA expression levels of corticotropin-releasing hormone (CRH), urocortin (UCN), urocortin 2 (UCN2), CRH receptor type 1 (CRH-R1) and CRH receptor type 2 (CRH-R2) in the hypothalamus were measured using real-time PCR. LPS injection in adulthood prolonged the estrous cycle in neonatal LPS-injected rats. LPS injection in adulthood decreased food intake and body weight in both neonatal LPS- and saline-injected rats, more so in the latter. Basal expressions of UCN2 and CRH-R2 mRNA were higher in neonatal LPS-injected rats than in saline-injected rats. These findings indicate that neonatal immune challenge influences the anti-stress regulation of the estrous cycle and feeding behavior in adulthood. Increased expression of UCN2 and CRH-R2 might enhance the sensitivity of the estrous cycle in suppressing the effects of LPS.