RESUMEN
Magnetic properties of dinuclear nickel(II) complex [Ni2(sym-hmp)2](BPh4)2·3.5DMF·0.5(2-PrOH) (1), where (sym-hmp)- is 2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate anion and DMF indicates dimethylformamide, were investigated using high-frequency and -field electron paramagnetic resonance (HFEPR). To magnetically characterize the mononuclear nickel(II) species forming the dimer, its two dinuclear zinc(II) analogues, [Zn2(sym-hmp)2](BPh4)2·3.5DMF·0.5(2-PrOH) (2) and [Zn2(sym-hmp)2](BPh4)2·2acetone·2H2O (2'), were prepared. One of them (2') was structurally characterized by X-ray diffractometry and doped with 5% mol nickel(II) ions to prepare a mixed crystal 3. From the HFEPR results on complex 1 obtained at 40 K, the spin Hamiltonian parameters of the first excited spin state (S = 1) of the dimer were accurately determined as |D1| = 9.99(2) cm-1, |E1| = 1.62(1) cm-1, and g1 = [2.25(1), 2.19(2), 2.27(2)], and for the second excited spin state (S = 2) at 150 K estimated as |D2| ≈ 3.5 cm-1. From these numbers, the single-ion zero-field splitting (ZFS) parameter of the Ni(II) ions forming the dimer was estimated as |DNi| ≈ 10-10.5 cm-1. The HFEPR spectra of 3 yielded directly the single-ion parameters for DNi = +10.1 cm-1, |ENi| = 3.1 cm-1, and giso = 2.2. On the basis of the HFEPR results, the previously obtained magnetic data (Sakiyama, H.; Tone, K.; Yamasaki, M.; Mikuriya, M. Inorg. Chim. Acta 2011, 365, 183) were reanalyzed, and the isotropic interaction parameter between the Ni(II) ions was determined as J = -70 cm-1 (Hex = -J SA·SB). Finally, density functional theory calculations yielded the J value of -90 cm-1 in a qualitative agreement with the experiment.
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Kisspeptin, which is encoded by the Kiss1 gene, and its receptor, the G protein-coupled receptor 54 (Kiss1r), play important roles in the regulation of reproductive functions in mammals. Several studies have shown that the Kiss1 and Kiss1r genes are expressed in the rat, primate, and human ovaries, and that the ovarian kisspeptin system plays a pivotal role in ovulation at the proestrous stage in adulthood. The purpose of this study was to evaluate development-related changes in the expression of ovarian Kiss1 and Kiss1r genes and in kisspeptin levels, and to identify the regulatory factors for these genes during the prepubertal period. The serum kisspeptin level was also measured to examine whether ovarian kisspeptin affects serum kisspeptin levels. Variations in the ovarian Kiss1 and Kiss1r mRNA levels were observed during the prepubertal period in female rats, with levels peaking around postnatal days 20 and 15, respectively. Nevertheless, the ovarian kisspeptin content per total protein level was stably maintained. Serum kisspeptin levels at postnatal days 30 and 35 were higher than those at earlier postnatal days. The pattern of the ovarian Kiss1 mRNA levels was similar to that of the serum luteinizing hormone (LH) levels, and the ovarian Kiss1 mRNA level increased after injection with human chorionic gonadotropin (HCG) on postnatal day 20, but not on postnatal days 10 and 30. These data indicate that ovarian Kiss1 and Kiss1r mRNA levels are increased on postnatal days 20 and 15, respectively, and that changes in the serum LH level and the ovarian sensitivity to LH may be involved in the alteration of ovarian Kiss1 mRNA levels.
Asunto(s)
Gonadotropina Coriónica/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Kisspeptinas/metabolismo , Ovario/metabolismo , Receptores de Kisspeptina-1/metabolismo , Animales , Femenino , Kisspeptinas/genética , Ovario/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Kisspeptina-1/genéticaRESUMEN
Purpose: To assess the kisspeptin concentrations in follicular fluid and their relationship with clinical outcomes during assisted reproductive technology. Methods: Thirty-nine patients who were aged 24-40 years and underwent oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection participated in this study. In 65 follicular fluid samples that had been obtained from 30 patients and their blood samples, the kisspeptin levels were measured in order to investigate the correlations with their gonadal hormone levels. Venous blood samples were collected from 14 patients to investigate their plasma kisspeptin levels across different phases of assisted reproductive technology. Results: The follicular fluid kisspeptin level was significantly higher than that of the plasma level and was positively associated with the follicular fluid estradiol concentration and with the serum estradiol and number of mature oocytes. In the plasma, the maximum concentration of kisspeptin was observed on the day of ovum pick-up and on the day of embryo transfer during ovarian stimulation for assisted reproductive technology. Conclusion: Kisspeptin was present in the follicular fluid and the plasma kisspeptin concentration was affected by ovarian stimulation. Kisspeptin appears to affect oocyte maturation and ovulation.
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Resistin is involved in the inflammatory response, as well as in insulin resistance. In rodents, resistin levels are partially regulated by ovarian hormones. Thus, ovariectomy-induced changes in resistin levels and their response to lipopolysaccharide (LPS)-induced septic stress were evaluated. Ovariectomized (OVX) rats exhibited higher serum resistin concentrations and visceral and subcutaneous white adipose tissue (WAT) resistin mRNA levels than sham-operated (sham) rats under the saline-injected (basal) conditions. The serum resistin levels of the gonadal intact male rats were higher than those of the sham rats, whereas the serum resistin levels of the male and OVX rats did not differ. In both the sham and OVX rats, the serum resistin concentration and the resistin mRNA levels of WAT were increased by LPS injection. At 24h after the LPS injection, no difference was detected in the serum resistin concentrations or WAT mRNA resistin levels between the sham and OVX rats. These results suggest that ovarian hormones partially regulate the basal resistin levels of female rats.
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Endotoxemia/inducido químicamente , Lipopolisacáridos/toxicidad , Ovariectomía , Resistina/metabolismo , Tejido Adiposo/metabolismo , Animales , Femenino , Masculino , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Resistina/sangre , Resistina/genéticaRESUMEN
PURPOSE: We evaluated the role of tumor necrosis factor alpha (TNFα) in rat ovulation and granulosa cell death of ovarian follicles during the periovulatory stage. METHODS: Immature rats primed with pregnant mare serum gonadotropin were injected intraperitoneally with human chorionic gonadotropin (hCG), and TNFα was injected into the bursa 48 h later. The total number of released oocytes was counted. Apoptosis was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the expression of cleaved caspase 3 and Bax/Bcl-2. Autophagy was assessed by the expression of light chain protein 3 (LC3) and autophagosomes under transmission electron microscopy. RESULTS: TNFα significantly decreased the number of released oocytes, and many unruptured follicles were observed. TUNEL analysis revealed a larger number of apoptotic cells, and the cleaved caspase 3 and Bax/Bcl-2 increased more than that of the control 12 h after hCG administration. Furthermore, the expression of LC3 wwas significantly higher than that of the control, and autophagosomes were observed in the cytoplasm. CONCLUSIONS: Our data indicated that TNFα is an important mediator of ovulation in terms of decreasing the number of released oocytes and inducing granulosa cell death of unruptured follicles via apoptosis and autophagy for remodeling ovarian tissues.
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The aim of this study, we evaluated a complex between thiourea (TU) and carbamazepine (CBZ) of a poorly soluble drug by using powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, X-ray crystallography and the solubility test. PXRD of TU/CBZ=2/1, 1/1, and 1/2 prepared by solvent evaporation (EVP) revealed characteristic diffraction peaks at 2θ = 6.7°, 8.8°, 13.5°, and 20.4°, therefore molecular interaction between TU and CBZ presumably occurred. Results of the FT-IR spectroscopy, asymmetric and symmetric NH stretching vibration of TU were shifted to high region by TU/CBZ = 2/1, 1/1, and 1/2 EVP. TU/CBZ = 2/1 and 1/1 EVP had absorption derived from TU. It was considered that complex were formed by TU/CBZ = 1/2. X-Ray crystallography of TU and CBZ revealed a crystal structure with one TU molecule arranged near two CBZ molecules. Molecules of the same type overlap in this layer. When doing a solubility test by using CBZ and samples of EVP, physical mixture and crystals in TU/CBZ = 1/2 to confirm the solubility in water of TU/CBZ complex, there is no difference with the CBZ. It considered that the structure of a complex differs from the tunnel structure of inclusion complexes that has been previously reported contribute to result it.
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Analgésicos no Narcóticos/química , Carbamazepina/química , Tiourea/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Modelos Moleculares , Solubilidad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
A novel electrophilic-type trifluoromethylthiolation reagent, a trifluoromethanesulfonyl hypervalent iodonium ylide, was designed and reacted well with various nucleophiles to afford the desired CF3S-substituted products. In situ reduction of the trifluoromethanesulfonyl group to give the trifluoromethylthio group, which is the key step in this process, was realized in the presence of copper(I) chloride.
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Aminas/química , Cobre/química , Hidrocarburos Fluorados/química , Indoles/química , Compuestos de Sulfhidrilo/química , Catálisis , Ésteres/química , Cetonas/química , Compuestos Onio/química , Oxidación-ReducciónRESUMEN
This report details the development of a spirobiindane-based chiral hypervalent iodine reagent, especially focusing on its structural elucidation for effective asymmetric induction of the chiral spiro center during the oxidative dearomatizing spirolactonization of naphthols. In this study we synthesized a new series of ortho-functionalized spirobiindane catalysts and demonstrated that the enantioselectivity can be dramatically improved by the presence of the substituents ortho to the iodine atom. The structural elucidation of a spirobiindane-based hypervalent iodine catalyst has led to further improvement in the stereoselective construction of the spiro center during the oxidative dearomatizing spirolactonization of naphthols. Thus, catalytic oxidation with the highest reported level of enantioselectivity in hypervalent iodine chemistry has been achieved with also an excellent level of asymmetric induction (92% ee for substrate 3a). As a result, this study, dealing with a series of modified iodine catalysts, can provide important clues about the transition state and reaction intermediate to help scientists understand the origin of the stereoselectivity. A plausible transition-state model and intermediate in the reaction for the stereoselective formation of spirolactone products are postulated by considering the ortho-substituent effect and the results of X-ray analysis. In this reaction model, the high enantiomeric excess obtained by using the spirobiindane catalysts could be well explained by the occupation of the equatorial site and extension of the surroundings around the hypervalent iodine bonds by the introduced ortho-substituent. Thus, this study would contribute to estimation of the chiral hypervalent iodine compounds in asymmetric reactions.
Asunto(s)
Indanos/química , Yodo/química , Lactonas/química , Naftoles/química , Compuestos de Espiro/química , Catálisis , Modelos Moleculares , EstereoisomerismoRESUMEN
The mol-ecule of the title compound, C(16)H(11)N(3)O(3), exists in the keto form and the C=O and N-H bonds are mutually cis in the crystal structure. There are two crystallographically independent mol-ecules per asymmetric unit with broadly similar structural data. The only noticeable difference between the two is the dihedral angles between the benzene and the quinoline rings: 1.04â (4) and 3.07â (4)°. In the structure, intra-molecular N-Hâ¯O(carbon-yl) and N-Hâ¯N(pyridine) hydrogen bonds exist but there is no evidence of formal inter-molecular hydrogen-bonding associations.
RESUMEN
The ins and outs of spin: Using the microporous coordination polymer {Fe(pz)[Pt(CN)(4)]} (1, pz=pyrazine), incorporating spin-crossover subunits, two-directional magnetic chemo-switching is achieved at room temperature. In situ magnetic measurements following guest vapor injection show that most guest molecules transform 1 from the low-spin (LS) state to the high-spin (HS) state, whereas CS(2) uniquely causes the reverse HS-to-LS transition.
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The crystal structure of a new magnesium(ii) complex, [Mg(dmso)6][BPh4]2 (1) (dmso: dimethylsulfoxide), was determined, and the reason for the observed structure was clarified by conformational analysis. For a dmso-ligand arm, three conformations, α, ß, and γ, are possible. The α-arm is the most energetically favourable and is suitable for reducing the steric repulsion between the arms; the ß-arm is less energetically favourable, but can be stabilized by interaction with surroundings (e.g. CHπ interaction); the γ-arm is not energetically favourable, but is effective in reducing the size of the complex cation. From the conformational analysis, the most stable conformer of the [Mg(dmso)6]2+ complex cation was found to be the α6 conformer, and the complex cation in dmso solution was predicted to exist as a mixture of α6, α5ß, and trans-α4ß2 species. On the contrary, in the crystal structure, the trans-ß2γ4 species, considered to be unstable, was observed. From the conformational analysis in the tetraphenylborate surroundings, the trans-ß2γ4 structure was found to become more stable, due to its small size suitable for crystal packing with bulky tetraphenylborate anions.
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Prenatal undernutrition and postnatal overnutrition increase the risk of some metabolic disorders in adulthood, and hypothalamic leptin resistance makes an important contribution to these effects. Leptin plays important roles in the maintenance of reproductive function, and its actions might be partially mediated by kisspeptin, which is a potent positive regulator of gonadotropin-releasing hormone. In this study, the effects of prenatal undernutrition and postnatal overnutrition on reproductive parameters and sexual maturation during the peripubertal period were evaluated. Rats subjected to prenatal undernutrition (IUGR) and fed a postnatal high-fat diet (HFD) (n = 7) exhibited 40% higher serum leptin levels and 30% lower hypothalamic Kiss1 (the gene encoding kisspeptin) mRNA levels than those subjected to prenatal undernutrition (IUGR) and fed a normal diet (n = 7). No such HFD-induced postnatal alterations were observed in the rats fed a normal diet during the prenatal period (control) (n = 7 per group). Although the consumption of the HFD did not affect the serum luteinizing hormone levels or body weight of the IUGR or control rats, it did promote vaginal opening in both groups (evaluated in 14 rats per group). These findings indicate that hypothalamic leptin resistance might occur in IUGR-HFD rats, but these changes do not influence downstream effectors of the reproductive endocrinological system. They also suggest that the relationships between nutritional conditions, body weight, reproductive factors, and sexual maturation are complex.
Asunto(s)
Hipotálamo/metabolismo , Kisspeptinas/genética , Leptina/sangre , Desnutrición/sangre , Desnutrición/patología , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/patología , ARN Mensajero/metabolismo , Animales , Animales Recién Nacidos , Peso Corporal , Femenino , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/metabolismo , Kisspeptinas/metabolismo , Masculino , Neuropéptidos/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Kisspeptina-1 , Receptores de Neuropéptido/genética , Receptores de Neuropéptido/metabolismoRESUMEN
Oxytocin (OT) affects the central nervous system and is involved in a variety of social and non-social behaviors. Recently, the role played by OT in energy metabolism and its organizational effects on estrogen receptor alpha (ER-α) during the neonatal period have gained attention. In this study, the developmental changes in the hypothalamic mRNA levels of OT, the OT receptor (OTR), and ER-α were evaluated in male and female rats. In addition, the fasting-induced changes in the hypothalamic mRNA levels of OT and the OTR were evaluated. Hypothalamic explants were taken from postnatal day (PND) 10, 20, and 30 rats, and the mRNA level of each molecule was measured. Hypothalamic OT mRNA expression increased throughout the developmental period in both sexes. The rats' hypothalamic OTR mRNA levels were highest on PND 10 and decreased throughout the developmental period. In the male rats, the hypothalamic mRNA levels of ER-α were higher on PND 30 than on PND 10. On the other hand, no significant differences in hypothalamic ER-α mRNA expression were detected among the examined time points in the female rats, although hypothalamic ER-α mRNA expression tended to be higher on PND 30 than on PND 10. Significant positive correlations were detected between hypothalamic OT and ER-α mRNA expression in both the male and female rats. Hypothalamic OT mRNA expression was not affected by fasting at any of the examined time points in either sex. These results indicate that hypothalamic OT expression is not sensitive to fasting during the developmental period. In addition, as a positive correlation was detected between hypothalamic OT and ER-α mRNA expression, these two molecules might interact with each other to induce appropriate neuronal development.
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Ayuno , Regulación del Desarrollo de la Expresión Génica/fisiología , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Oxitocina/genética , ARN Mensajero/metabolismo , Receptores de Oxitocina/genética , Caracteres Sexuales , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Masculino , Oxitocina/metabolismo , Distribución Aleatoria , Ratas , Receptores de Oxitocina/metabolismo , Estadística como AsuntoRESUMEN
Hypothalamic pro-inflammatory cytokine expression exhibits a weaker response to lipopolysaccharides (LPS) during the early neonatal period than during the later developmental period. Although toll-like receptor 4 (TLR4), which recognizes bacterial molecules, activates pro-inflammatory cytokine responses, the developmental changes in hypothalamic TLR4 expression have not been evaluated. In this study, the hypothalamic TLR4 mRNA levels of saline-injected and LPS-injected rats were measured during the neonatal, pre-pubertal, and post-pubertal periods. The rats' hypothalamic TLR4 mRNA levels gradually increased from the neonatal to pubertal period and were altered by the injection of LPS at all examined ages (postnatal day (PND) 5, 15, 25, and 42). LPS injection resulted in decreased hypothalamic TLR4 mRNA expression at PND5, whereas it increased hypothalamic TLR4 mRNA expression at PND15, 25, and 42. After the injection of LPS, the hypothalamic mRNA levels of the pro-inflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor α, and IL-6 were attenuated during the early developmental period and increased acutely on PND42. The expression profiles of these pro-inflammatory cytokines exhibited similar, but not entirely consistent, changes to those displayed by TLR4 during the developmental period. Hypothalamic TLR4 mRNA expression gradually increased throughout the developmental period, whereas the mRNA expression levels of the pro-inflammatory cytokines increased acutely at PND42. Thus, it is assumed that hypothalamic TLR4 hypoactivity contributes to the low sensitivity of pro-inflammatory cytokines to LPS during the early developmental period.
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Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hipotálamo/metabolismo , Lipopolisacáridos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/patología , ARN Mensajero/metabolismo , Receptor Toll-Like 4/genética , Factores de Edad , Animales , Animales Recién Nacidos , Citocinas/genética , Citocinas/metabolismo , Femenino , Hipotálamo/crecimiento & desarrollo , Embarazo , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas , Receptor Toll-Like 4/metabolismoRESUMEN
Neuropeptide Y (NPY) is an important hypothalamic orexigenic neuropeptide that acts in the brain. It has been established that the fasting-induced up-regulation of NPY expression is mainly caused by a reduction in the activity of leptin, which is a hormone secreted by adipose tissue. We have reported that in female rats hypothalamic NPY mRNA expression does not respond to fasting during the early neonatal period, but subsequently becomes sensitive to it later in the neonatal period. In this study, we compared the developmental changes in the responses of NPY and leptin expression to fasting between male and female rats during the neonatal to pre-pubertal period. Fasting was induced by maternal deprivation during the pre-weaning period (postnatal days 10 and 20) and by food deprivation during the post-weaning period (postnatal day 30). Hypothalamic NPY mRNA expression was not affected by fasting on postnatal day 10, whereas it was increased by fasting on postnatal day 20 and 30 in both males and females. On the other hand, the serum leptin level was decreased by fasting at all examined ages in both sexes. Namely, hypothalamic NPY mRNA expression was not correlated with the reduction in the serum leptin level at postnatal day 10 in either sex. Under the fasted conditions, the hypothalamic NPY mRNA levels of the males were higher than those of the females on postnatal days 20 and 30, whereas no such differences were observed under the normal nourishment conditions. The serum leptin levels observed under the fasted conditions did not differ between males and females at any examined age. These results suggest that some hypothalamic NPY functions develop during the neonatal period and that there is no major difference between the sexes with regard to the time when NPY neurons become sensitive to fasting. They also indicate that hypothalamic NPY expression is more sensitive to under-nutrition in male rats than in female rats, at least during the pre-pubertal period.
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Privación de Alimentos/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Hipotálamo/metabolismo , Leptina/genética , Neuropéptido Y/genética , ARN Mensajero/metabolismo , Caracteres Sexuales , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Femenino , Leptina/metabolismo , Masculino , Neuropéptido Y/metabolismo , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
It has been reported that intrauterine undernutrition is closely associated with the pathogeneses of certain diseases in adulthood; i.e., insulin resistance and diabetes, and that leptin resistance plays a pivotal role in the pathology of such intrauterine growth restriction (IUGR)-related conditions. Therefore, examinations of IUGR-induced leptin resistance in early developmental period are important for protecting against future disease. In this study, the effects of prenatal undernutrition on the serum leptin levels and central leptin responses of rats during the neonatal and/or pre-pubertal period were examined. The 50% food-restricted undernourished dams' offspring (UNO) exhibited a significantly lower birth weight than the normal nutrition dams' offspring (NNO). However, the UNO grew rapidly, and their mean body weight had caught up with that of the NNO by postnatal day 8. Thus, there were no significant differences between the body weights of the two groups at postnatal day 12, 16, 20, or 28. The serum leptin levels of the UNO were significantly higher than those of the NNO at postnatal days 20 and 28. At postnatal day 28, no significant difference in the hypothalamic mRNA level of neuropeptide Y, which is the main target of leptin, or that of ObRb, which is the leptin receptor, was detected between the NNO and UNO. The chronic intracerebroventricular injection of leptin attenuated body weight gain in both the NNO and UNO; however, there were no significant differences between the body weights of the two groups at any of the examined postnatal time points, indicating that the UNO and NNO exhibited similar central sensitivity to leptin during the pre-pubertal period. These results suggest that prenatal undernutrition induces leptin resistance until the neonatal to pre-pubertal period and that these alterations might be caused by impaired transportation of leptin to central tissues.
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Envejecimiento/sangre , Retardo del Crecimiento Fetal/fisiopatología , Trastornos de la Nutrición del Lactante/fisiopatología , Leptina/administración & dosificación , Leptina/sangre , Complicaciones del Embarazo/fisiopatología , Aumento de Peso/efectos de los fármacos , Animales , Animales Recién Nacidos , Peso al Nacer/efectos de los fármacos , Femenino , Retardo del Crecimiento Fetal/prevención & control , Humanos , Recién Nacido , Inyecciones Intraventriculares , Masculino , Embarazo , Pubertad/sangre , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Prokineticin (PK2) and its receptors (PKRs) are expressed in several regions of the central nervous system, including the hypothalamus. It has been reported that PK2 inhibits food intake via PKR1 and that the hypothalamic PK2 mRNA levels of adult rodents were reduced by food deprivation. However, some hypothalamic factors do not exhibit sensitivity to undernutrition in the early neonatal period, but subsequently become sensitive to it during the neonatal to pre-pubertal period. In this study, we investigated the changes in the sensitivity of hypothalamic PK2 and PKR1 mRNA expression to fasting during the developmental period in male rats. Under the fed conditions, the rats' hypothalamic PK2 and/or PKR1 mRNA levels were higher on postnatal day (PND) 10 than on PND20 or PND30. In addition, the hypothalamic PK2 and/or PKR1 mRNA levels of the male rats were higher than those of the females at all examined ages (PND10, 20, and 30). Hypothalamic PK2 mRNA expression was decreased by 24h fasting at PND10 and 30, but not at PND20. In addition, hypothalamic PKR1 mRNA expression was decreased by 24h fasting at PND10, but not at PND20 or 30. These results indicate that both PK2 and PKR1 are sensitive to nutritional status in male rats and that this sensitivity has already been established by the early neonatal period. It can be speculated that the PK2 system might compensate for the immaturity of other appetite regulatory factors in the early neonatal period.
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Privación de Alimentos/fisiología , Hormonas Gastrointestinales/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Neuropéptidos/metabolismo , Receptores de Péptidos/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Femenino , Hormonas Gastrointestinales/genética , Masculino , Neuropéptidos/genética , Embarazo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/genética , Factores SexualesRESUMEN
Glucocorticoid secretion is a key endocrine response to stress. It has been reported that prenatal stress induces long-lasting alterations in body weight regulation systems, which persist after the stress has ceased. In this study, the long-term effects of prenatal glucocorticoid exposure on body weight changes and the expression of appetite-regulating factors were examined in female rats. Pregnant rats were given normal drinking water (control) or dexamethasone (1 µg/mL) dissolved in drinking water (DEX) from day 13 of pregnancy until delivery. Then, the body weight change, serum leptin levels, and hypothalamic NPY mRNA levels of their offspring were examined. The DEX dams gained significantly less body weight during pregnancy than the control dams. The DEX dams' offspring exhibited a significantly lower birth weight than the offspring of the control dams, and the same was true for body weight at postnatal days 20 and 28. The offspring of the DEX dams displayed significantly higher serum leptin levels and significantly lower hypothalamic NPY mRNA levels compared with the offspring of the control dams. Significant inverse correlations were detected between body weight and the serum leptin level, and between the serum leptin level and the hypothalamic NPY mRNA level. On the other hand, a significant positive correlation was detected between body weight and the hypothalamic NPY mRNA level. These results indicate that leptin production is increased in a long-lasting manner in offspring exposed to glucocorticoids during the prenatal period and that this results in attenuated body weight gain and hypothalamic NPY expression during the pre-pubertal period.
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Peso Corporal/efectos de los fármacos , Glucocorticoides/efectos adversos , Hipotálamo/metabolismo , Leptina/sangre , Neuropéptido Y/metabolismo , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Dexametasona/farmacología , Femenino , Hipotálamo/efectos de los fármacos , Masculino , Neuropéptido Y/genética , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Prokineticin 2 (PK2) is highly expressed in several regions of the central nervous system, including the hypothalamus. Recently, it has been suggested that PK2 plays a role in appetite regulation. In adult male rodents, the administration of PK2 decreased food intake, and PK2 mRNA expression was reduced by food deprivation. Usually, the changes in the expression levels of appetite-regulating factors induced in response to fasting are not fully established during the neonatal period. Thus, we investigated the developmental changes in hypothalamic PK2 mRNA expression and the alterations in hypothalamic PK2 mRNA expression induced by fasting during the pre-pubertal period in female rats. The changes in hypothalamic neuropeptide Y (NPY) mRNA expression were also examined because NPY is a potent appetite regulatory factor. Hypothalamic PK2 mRNA expression was extremely high during the early neonatal period (postnatal day (PND) 5) compared with that observed during subsequent periods (PND15, 25, and 42), while hypothalamic NPY mRNA expression did not differ among any of the examined periods. A fasting-induced reduction in hypothalamic PK2 mRNA expression was observed on PND5, but no fasting-induced increase in hypothalamic NPY mRNA expression was seen during the same period. In addition, the fasting-induced reduction in hypothalamic PK2 mRNA expression observed on PND5 was more marked than that seen on PND25. These results suggest that the sensitivity of hypothalamic PK2 expression to undernutrition develops during the early neonatal period, when the responses of other appetite regulatory factors to such pressures remain immature.