RESUMEN
Nutrient availability is a determinant of reproductive success. It is well known that inadequate nutrition results in reproductive failure due to a number of factors including delay of puberty or anoestrous in post-pubertal animals. The lack of nutrients is detected primarily by changes in circulating nutrient molecules and hormones and communicated directly or indirectly to the hypothalamus and brain stem for integration. The general effect is that low nutrition leads to increased appetite stimulation and reduced reproductive performance. When nutrition is adequate, the reverse is true. Both aspects will be the focus of this review. One result of the lack of nutrients is a reduction in luteinizing hormone (LH) concentrations and pulse frequency. Nutrient signals, such as glucose availability, hormonal signals, such as insulin and leptin, and neuroendocrine signals, such as neuropeptide Y and corticotropin-releasing hormone, have been clearly demonstrated to interact to produce changes in LH and reproductive success. Other signals, such as fatty acids, ghrelin, agouti-related peptide, melanin-concentrating hormone, orexin, melanocyte-stimulating hormone, kisspeptin, neurokinin, dynorphin and gonadotropin inhibitory hormone may also play a role in integrating nutrition and reproduction. This review will focus on the major features of the reciprocal control of appetite and reproduction in sheep.
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Hipotálamo/fisiología , Estado Nutricional/fisiología , Reproducción/fisiología , Ovinos/fisiología , Animales , Regulación del Apetito , Hormona Liberadora de Corticotropina , Ácidos Grasos , Femenino , Glucosa , Hormonas , Insulina , Leptina , Hormona Luteinizante/sangre , Hormona Luteinizante/fisiología , Masculino , Neuropéptido Y , NeuropéptidosRESUMEN
This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise nutritional protocols: (1) placebo (EX); (2) carbohydrate only (CHO); and (3) essential amino acid/carbohydrate (EAA/CHO). Samples were analyzed for growth hormone (GH), free IGF-I, IGFBP-1, IGFBP-2, insulin, hematocrit, hemoglobin, serum leucine, matrix metalloproteinase-9 (MMP-9) proteolytic activity, and presence of IGFBP-3 protease activity. No evidence for IGFBP-3 proteolysis was observed. Significant increases in [free IGF-I] and [leucine] were observed in the EAA/CHO group only. Significant differences were noted in [IGFBP-1] and [IGFBP-2] across conditions. Significant increases in [GH] and MMP-9 activity were observed in all groups. These results indicate that post-exercise macronutrient ratio is a determinant of [free IGF-I], [IGFBP-1 and -2] and may play a role in modulating the IGF-I axis in vivo.
Asunto(s)
Aminoácidos Esenciales/metabolismo , Suplementos Dietéticos/estadística & datos numéricos , Ejercicio Físico , Regulación de la Expresión Génica , Factor I del Crecimiento Similar a la Insulina/genética , Adulto , Metabolismo de los Hidratos de Carbono , Suplementos Dietéticos/análisis , Hormona del Crecimiento/sangre , Humanos , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Adulto JovenRESUMEN
Kisspeptin, a regulator of gonadotropin-releasing hormone, has been hypothesized as an integrator of nutrition and hormones critical to metabolism and the regulation of reproduction. Growth hormone (GH) is necessary for optimal reproduction and recent evidence suggests that its secretion may be influenced by kisspeptin. The objectives of this study were to determine whether the effect of kisspeptin to stimulate GH release is due to an interaction with growth hormone-releasing hormone (GHRH) or somatostatin (SS), or an effect at the hypothalamus. Intravenous injection and infusion of kisspeptin [500 pmol/kg BW (650 ng/kg)/h × 5 h] to cows (n = 5) increased serum concentrations of luteinizing hormone (LH) but not GH. Pretreatment with kisspeptin injection and infusion in cows (n = 5) reduced the stimulatory effect of GHRH (0.05 µg/kg BW) on GH secretion. However, the magnitude of the GH response to GHRH (assessed by incremental AUC) was not affected by kisspeptin. In these same cows, administration of kisspeptin prevented the increase in GH induced by SS infusion (0.5 µg/kg BW/ h × 1.5 h) withdrawal. Peripheral administration of kisspeptin [200 and 1,000 pmol/kg BW (260 and 1,300 ng/kg)] increased serum concentrations of LH but not GH in ewes (n = 8). However, concentrations of GH were stimulated by central kisspeptin treatment [100 and 200 pmol/kg BW (130 and 260 ng/kg)] in ewes. In addition to activating the gonadotropic axis, kisspeptin can activate the somatotropic axis in ruminants. Present data support the concept of a central site of action for this effect.
Asunto(s)
Hormona del Crecimiento/sangre , Adenohipófisis/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Área Bajo la Curva , Bovinos , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/metabolismo , Hormona del Crecimiento/metabolismo , Kisspeptinas , Hormona Luteinizante/sangre , Ovariectomía , Adenohipófisis/efectos de los fármacos , Radioinmunoensayo , Ovinos , Somatostatina/administración & dosificación , Proteínas Supresoras de Tumor/administración & dosificaciónRESUMEN
Disease in animals is a well-known inhibitor of growth and reproduction. Earlier studies were initiated to determine the effects of endotoxin on pituitary hormone secretion. These studies found that in sheep, growth hormone (GH) concentration was elevated, whereas insulin-like growth factor-I (IGF-I) was inhibited, as was luteinizing hormone (LH). Examination of the site of action of endotoxin in sheep determined that somatotropes expressed the endotoxin receptor (CD14) and that both endotoxin and interleukin-I beta activated GH secretion directly from the pituitary. In the face of elevated GH, there is a reduction of IGF-I in all species examined. As GH cannot activate IGF-I release during disease, there appears to be a downregulation of GH signalling at the liver, perhaps related to altered nitration of Janus kinase (JAK). In contrast to GH downregulation, LH release is inhibited at the level of the hypothalamus. New insights have been gained in determining the mechanisms by which disease perturbs growth and reproduction, particularly with regard to nitration of critical control pathways, with this perhaps serving as a novel mechanism central to lipopolysaccharide suppression of all signalling pathways. This pathway-based analysis is critical to the developing novel strategies to reverse the detrimental effect of disease on animal production.
Asunto(s)
Citocinas/farmacología , Endotoxinas/farmacología , Hormona del Crecimiento/sangre , Sistemas Neurosecretores/fisiología , Reproducción/efectos de los fármacos , Ovinos/fisiología , Animales , Animales Domésticos , Femenino , Hormona del Crecimiento/fisiología , Hormona Luteinizante/metabolismo , Masculino , Reproducción/fisiología , Ovinos/sangre , Ovinos/crecimiento & desarrollo , Transducción de SeñalRESUMEN
The present research was conducted to model potential mechanisms through which IGFBPs might be affected by a key proinflammatory response initiating cytokine tumor necrosis factor (TNF-)-alpha. Madin-Darby bovine kidney epithelial (MDBK) cells, known to release IGFBPs in response to several stimuli, were grown under several conditions and challenged with forskolin (F) or recombinant TNF-alpha for 24h. Forskolin increased IGFBP-3 gene expression and media content of BP-3 protein. TNF-alpha increased basal and augmented F-mediated IGFBP-3 gene expression. However, TNF-alpha effects on the measurable media content of IGFBPs were influenced by culture conditions; in the absence of added protease inhibitors (PIs) or sufficient media albumin concentration (high BSA, 1mg/ml), the effect of TNF-alpha was to decrease (P<0.02) measurable IGFBPs. In the presence of PI and high BSA, media IGFBP-3 levels were shown to be increased by TNF-alpha consistent with the gene expression data. Changes in media IGFBP-3 protease activity were examined further to explain the observed effects of TNF-alpha on production and destruction of IGFBPs in media. When recombinant human IGFBP-3 (500 ng/ml) was added to PI-free, low BSA 100 microg/ml) media from TNF-treated MDBK cells, less than 10% of the BP-3 was recognizable by Western blot in 30 min; conversely, inclusion of High BSA and PI in media resulted in attenuation of the protease effect on the IGFBPs. The data suggest that the MDBK model of cellular response to proinflammatory stimulus is affected by culture conditions and that TNF-alpha affects media content of IGFBPs through effects on IGFBP gene expression coupled with degradation of IGFBPs via enhanced proteolytic enzyme release.
Asunto(s)
Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Riñón/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Animales , Bovinos , Línea Celular , Expresión Génica/efectos de los fármacos , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Riñón/efectos de los fármacos , Proteínas RecombinantesRESUMEN
Leukemia inhibitory factor (LIF) has been suggested to function as a potent inhibitor of feed intake in rodents. In sheep, intravenous injection of lipopolysaccharide (LPS) resulted in an increase in gene expression for LIF in the arcuate nucleus ( < 0.01). In the same experiment, agouti related protein (AgRP) expression was elevated ( < 0.05) but there were no effects on proopiomelanocortin expression. Another group of sheep were provided intracerebroventricular (ICV) injections of LIF at 250, 500, 1,000, and 2,500 ng per sheep. Cumulative feed intake was inhibited by the 1,000- and 2,500-ng doses at 8 and 10 h after ICV injection ( < 0.03). All doses of LIF elevated temperature above 40°C, indicating a fever. When AgRP was intracerebroventricularly injected before LIF, there was no effect of LIF to reduce feed intake, suggesting the LIF inhibition of feed intake is consistent with the concept that the effect is mediated by the melanocortin-4 receptor. In an experiment to determine whether endocrine and metabolic effects of LIF were similar to reported effects of LPS, sheep were intracerebroventricularly injected with 2,500 ng LIF, and blood samples were collected at 10-min intervals for 6 h for assay of LH, samples from the first 3 h were assayed for GH, and samples at 30-min intervals were assayed for glucose and free fatty acids. The effect of treatment and treatment × time interaction was significant, indicating elevated plasma free fatty acids ( < 0.03 and < 0.001, respectively) and glucose ( < 0.01 and < 0.0001, respectively). There was also a treatment × time interaction on circulating concentrations of LH such that LIF caused LH to decrease ( < 0.0001). Additionally, there was a tendency for LIF treatment to increase circulating concentrations of GH (P = 0.0874). The effects of LIF on feed intake and other parameters was similar to the effects of LPS and leads to a hypothesis that LIF expression in response to LPS may be a component of the mechanism for feed intake inhibition and perhaps for changes in selected hormone and metabolites in disease models.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Factor Inhibidor de Leucemia/farmacología , Lipopolisacáridos/toxicidad , Ovinos/fisiología , Proteína Relacionada con Agouti/administración & dosificación , Proteína Relacionada con Agouti/farmacología , Animales , Apetito/efectos de los fármacos , Ingestión de Alimentos/fisiología , Ácidos Grasos no Esterificados/sangre , Regulación de la Expresión Génica , Factor Inhibidor de Leucemia/administración & dosificación , Hormona Luteinizante , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/metabolismo , Factores de TiempoRESUMEN
Studies were performed to isolate peptides displaying antigonadotropic properties from bovine pineal tissue. Inhibition of compensatory ovarian hypertrophy in adult mice was used as an index of activity to guide the purification of a bovine pineal extract in order to isolate these antigonadal peptides. Defatted bovine pineal glands were extracted with acetic acid and further purified by cation-exchange chromatography, gel filtration and paper electrophoresis. The electrophoretogram revealed sixteen ninhydrin spots, of which four were antigonadotropic. One of these fractions was subjected to paper chromatography which yielded two antigonadal fractions. Amino acid analysis of each of these fractions indicated that one was in pure form and the sequence was found to be threonylserinyllysine. The other fraction was heterogeneous, but contained no lysine. Analysis of the amino acid content of the other antigonadal fractions obtained after electrophoresis indicated the possibility that other peptides were present, but did not suggest the presence of arginine vasotocin.
Asunto(s)
Gonadotropinas/antagonistas & inhibidores , Antagonistas de Hormonas/aislamiento & purificación , Oligopéptidos/aislamiento & purificación , Glándula Pineal/análisis , Secuencia de Aminoácidos , Animales , Bovinos , Cromatografía en Gel , Femenino , Antagonistas de Hormonas/farmacología , Hipertrofia/prevención & control , Oligopéptidos/farmacología , Ovario/patologíaRESUMEN
Reduced appetite combined with increased metabolic rate and decreased lean body mass is a major consequence of disease and other stressors. Studies in rodent species suggest that an understanding of appetite regulation may provide methodologies for intervention to prevent the deterioration of body mass such as observed with cancer or infectious diseases. For example, melanocortin-4 receptor (MC4-R) antagonists have shown a remarkable ability to reverse or prevent cachexia in rodents with sarcoma or treated with endotoxin. Studies in sheep have indicated that a number of peptide neurotransmitters may have a role in regulating appetite in this species. For example, agouti related protein mRNA and protein levels are dramatically altered with fasting in sheep. Moreover, agouti related protein, neuropeptide Y, melanin concentrating hormone and orexin are potent stimuli to increase feed intake in sheep. Recent studies have indicated that one of these neurotransmitters, NPY, can work in principal to improve appetite in endotoxin-treated sheep. Current studies are examining the role that MC4-R antagonists may have in the prevention or correction of body mass wasting diseases as well as practical applications in animal production.
Asunto(s)
Modelos Animales de Enfermedad , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Receptor de Melanocortina Tipo 4/fisiología , Ovinos , Proteína Relacionada con Agouti , Animales , Regulación del Apetito , Caquexia/tratamiento farmacológico , Caquexia/fisiopatología , Enfermedad , Ayuno , Trastornos de Alimentación y de la Ingestión de Alimentos/tratamiento farmacológico , Alimentos , Péptidos y Proteínas de Señalización Intercelular , Neuropéptidos/fisiología , Proteínas/fisiología , Enfermedades de las Ovejas/fisiopatologíaRESUMEN
Melanin-concentrating hormone (MCH) stimulates feeding when injected intracerebroventricularly (ICV) in rats. At present it is not clear whether the function of MCH is similar in ruminants, which are species with a continuous delivery of nutrients. Therefore the current investigation sought to determine the role of MCH in sheep. In the first experiment, six, castrate male sheep were satiated and received one of four treatments [saline, 0.1, or 1.0 nmol/kg MCH, and NPY (0.1 nmol/kg)] injected ICV over 30s, then infused ICV for 6 h ( approximately 500 microl/h). Food intake was measured for 2 h before and at 2, 4, 6, 8, 12 and 24 h. In this experiment, feed intake was increased (PAsunto(s)
Ingestión de Alimentos/efectos de los fármacos
, Hormonas Hipotalámicas/administración & dosificación
, Melaninas/administración & dosificación
, Hormonas Hipofisarias/administración & dosificación
, Ovinos/fisiología
, Animales
, Secuencia de Bases
, Ingestión de Alimentos/fisiología
, Privación de Alimentos/fisiología
, Hormonas Hipotalámicas/genética
, Hipotálamo/efectos de los fármacos
, Hipotálamo/metabolismo
, Inmunohistoquímica/veterinaria
, Inyecciones Intraventriculares/veterinaria
, Masculino
, Melaninas/genética
, Datos de Secuencia Molecular
, Neuropéptido Y/metabolismo
, Hormonas Hipofisarias/genética
, ARN/química
, ARN/genética
, Distribución Aleatoria
, Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria
, Alineación de Secuencia
, Ovinos/metabolismo
RESUMEN
The dog pituitary pars intermedia (PI) appears to consist of relative large numbers of ACTH-containing cells in addition to the more abundant alpha MSH-containing cells. Since regulation of PI secretion probably varies across mammalian species, this study was undertaken to identify substances potentially involved in the control of dog PI POMC peptide secretion and to determine if these substances altered the secretion of immunoreactive (IR) ACTH and IR-alpha MSH in a parallel fashion. Pituitary neurointermediate lobes from dogs were collected and dispersed, and the PI cells obtained were perifused. For comparison, rat PI and pars distalis (PD) cells as well as dog PD cells were similarly collected and perifused. Dog PI cells secreted IR-alpha MSH at a basal rate of 125 +/- 59 (mean +/- SD) pg/min.10(5) cells and IR-ACTH at a rate of 40 +/- 9 pg/min.10(5) cells (molar IR-alpha MSH/IR-ACTH = 10). In contrast, secretion rates for IR-alpha MSH and IR-ACTH from perifused rat PI cells were 171 +/- 108 and 3 +/- 2 pg/min.10(5) cells, respectively (molar IR-alpha MSH/IR-ACTH = 179). Using Sephadex G-50 gel filtration chromatography, virtually all of the IR-beta-endorphin secreted by dog PI cells eluted near beta-endorphin (1-31). In addition, all of the IR-alpha MSH secreted by dog PI cells coeluted with synthetic alpha MSH on the G-50 column, but IR-ACTH appeared in two peaks, one eluting near porcine ACTH-(1-39) and another, apparently larger mol wt species. Dopamine and somatostatin were found to inhibit the secretion of IR-alpha MSH and IR-ACTH from perifused dog PI cells in a parallel and dose-dependent fashion. Norepinephrine and epinephrine similarly inhibited POMC peptide secretion, but this effect was blocked by haloperidol, suggesting that it was mediated through a dopamine receptor. CRF stimulated the secretion of both hormones from dog PI, and this effect was abolished by treatment of the cells with either dopamine or somatostatin. Cortisol had no effect on either basal or CRF-stimulated secretion of IR-alpha MSH or IR-ACTH from dog PI cells, but it did inhibit CRF-stimulated IR-ACTH from perifused dog PD. These results suggest that 1) dog PI secretes considerably more IR-ACTH than that in the rat; 2) the probable separate cell sources of IR-alpha MSH and IR-ACTH in dog PI are regulated in an identical fashion; and 3) dopamine, somatostatin, and CRF may function in the physiological or pathophysiological regulation of dog PI.
Asunto(s)
Péptidos/metabolismo , Hipófisis/metabolismo , Proopiomelanocortina/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Animales , Células Cultivadas , Cromatografía en Gel , Perros , Técnicas In Vitro , Hormonas Estimuladoras de los Melanocitos/metabolismo , Perfusión , Hipófisis/citología , RatasRESUMEN
Rapid onset metabolic impairments accompany the initiation of the acute phase response to many disease stresses, whereas more chronic metabolic perturbations may prolong the recovery period. In the present experiment the application of a mild endotoxin challenge [lipopolysaccharide (LPS)] alone or additive to a chronic subclinical parasitic infection (Sarcocystis cruzi; LPS + PI) in calves was used as a model to investigate and define a dynamic axis coordinated between adrenomedullin (AM) and nitric oxide in response to immune challenge. Plasma AM and NO2/NO3 concentration responses after LPS (0.45 microg/kg, iv) were rapid in onset and of higher magnitude and longer duration in PI + LPS calves than in those challenged with LPS alone. The post-LPS increase in plasma insulin was significantly greater in PI + LPS than in LPS; following refeeding of calves, insulin secretion was most blunted in PI + LPS calves, consistent with the inhibitory effects of NO and AM on insulin secretion. A more chronic response to the immune challenge (organ specific) was in evidence in tissues harvested 24 h after LPS challenge. Where lung and liver showed no immunostaining for inducible nitric oxide (iNOS), iNOS immunostaining was present in the pancreas, localized to islets only. The percentages of iNOS-immunopositive cells in islets were 1.7%, 21%, 6.7%, and 24% for control (C; saline infused), PI, LPS, and PI + LPS calves, respectively. AM immunostaining was not evident in the liver and was present, but not differentially affected by treatment, in airway epithelium in the lung. The number of islet cells with positive immunostaining for AM was increased in LPS, PI, and PI + LPS calves. The percentages ofAM-immunopositive cells in islets were 8%, 27%, 20%, and 33% for C, PI, LPS, and PI + LPS, respectively. Immunostaining for AM and iNOS was colocalized with cells positive for pancreatic polypeptide. By triple label confocal fluorescence immunocytochemistry, colocalization of intense AM and iNOS immunostaining was confirmed in peripheral islet cells. A weaker, more diffuse iNOS signal was also apparent in insulin-containing cells in PI + LPS. We conclude that chronic low level infection potentiates the severity of metabolic perturbations that arise with additive sudden onset immune challenge, as can occur with bacterial toxins. These metabolic disturbances are reflected in and possibly mediated by early onset increases in plasma tumor necrosis factor-alpha, insulin, and AM and up-regulated iNOS activity. These acute complications rapidly progress into a more chronic state characterized by diminished insulin response to feeding stimulus and colocalized increases in pancreatic islet AM and iNOS. The pancreatic responses in AM and iNOS may play a major role in mediating prolonged disturbances in nutrient use by tissues through their influences on temporal patterns of pancreatic hormone secretion during chronic illness.
Asunto(s)
Islotes Pancreáticos/metabolismo , Lipopolisacáridos/farmacología , Óxido Nítrico Sintasa/metabolismo , Péptidos/metabolismo , Estrés Fisiológico/sangre , Adrenomedulina , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/parasitología , Inmunohistoquímica , Islotes Pancreáticos/química , Hígado/química , Pulmón/química , Microscopía Fluorescente , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa de Tipo II , Péptidos/análisis , Péptidos/sangre , Sarcocistosis/inmunología , Sarcocistosis/veterinaria , Estrés Fisiológico/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I (IGF-I) are important hormonal peptides supporting thymic function and affecting growth throughout the body, particularly in the prepubescent period, several components of the GH/IGF-I pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGF-binding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1 mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.
Asunto(s)
Gangliosidosis GM1/veterinaria , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Envejecimiento , Animales , Gatos , Gangliósido G(M1)/genética , Gangliosidosis GM1/metabolismo , Hormona del Crecimiento/genética , Hormona del Crecimiento/farmacología , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Factor I del Crecimiento Similar a la Insulina/genética , Mutación , Hipófisis/metabolismo , ARN Mensajero/metabolismoRESUMEN
Beagle dogs were given saline, insulin or the dopamine antagonist, haloperidol, to examine peripheral concentrations of immunoreactive (ir)-pro-opiomelanocortin (POMC) peptides resulting from pars distalis or pars intermedia stimulation. Six beagles were given each test substance on separate occasions with and without dexamethasone pretreatment. Plasma was assayed directly for glucose, ir-ACTH, ir-alpha-MSH, cortisol and, after Sephadex G-50 Fine gel filtration chromatography, for ir-beta-lipotrophin (ir-beta-LPH) and ir-beta-endorphin (ir-beta-END) content. Injection of 0.5 units insulin/kg lowered (P less than 0.01) plasma glucose from 4.9 +/- 0.3 mmol/l (mean +/- S.D., saline controls) to 2.3 +/- 0.5 mmol/l, coincident with increasing ir-ACTH (9.5 +/- 3.1 to 106 +/- 54 pmol/l), cortisol (52 +/- 27 to 221 +/- 27 nmol/l), ir-beta-LPH (not detectable to 34 +/- 18 pmol/l) and ir-beta-END (not detectable to 52 +/- 22 pmol/l). Plasma ir-alpha-MSH concentrations were not affected by insulin. Pretreatment with dexamethasone abolished the ir-ACTH, cortisol, ir-beta-LPH and ir-beta-END increases in response to 0.75 units insulin/kg. Haloperidol (1 mg/kg) increased (P less than 0.01) plasma ir-ACTH (to 103 +/- 63 pmol/l), cortisol (to 243 +/- 11 nmol/l), ir-beta-LPH (to 16 +/- 6 pmol/l), ir-beta-END (to 136 +/- 73 pmol/l) and additionally raised ir-alpha-MSH (7 +/- 8 pmol/l in saline controls to 131 +/- 80 pmol/l after haloperidol).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Perros/fisiología , Fragmentos de Péptidos/metabolismo , Adenohipófisis/metabolismo , Proopiomelanocortina/metabolismo , Hormona Adrenocorticotrópica/sangre , Animales , Glucemia/análisis , Dexametasona , Femenino , Haloperidol , Insulina , Masculino , alfa-MSH/sangre , betaendorfina/sangre , beta-Lipotropina/sangreRESUMEN
Concentrations of immunoreactive (i) ACTH, cortisol and thyroxine were determined in plasma samples obtained at 20-min intervals for 25 h in nine normal and two adrenalectomized dogs. The dogs were exposed to a 12 h light: 12 h darkness photoperiod for 30 days before the sampling period. Episodic secretion of iACTH and cortisol was evident in each normal dog, with an average of 9.0 iACTH peaks and 10.1 cortisol peaks in a 24-h period. Levels of iACTH and cortisol were significantly correlated in each normal dog, but periods of dissociation between levels of the two hormones were apparent. A sex difference in 24-h mean iACTH and cortisol levels, numbers of cortisol peaks, and amplitude of iACTH peaks was observed, with females showing higher mean levels and greater peak frequency and amplitude in each instance. Adrenalectomy resulted in a 50- to 150-fold increase in mean iACTH concentrations with an apparent increase in iACTH peak amplitude. Cortisol levels were unchanging in the adrenalectomized dogs. Thyroxine concentrations showed episodic variation in each of the normal dogs, but the mean number of peaks (3.3/24-h period) was considerably less than for iACTH or cortisol. Female dogs a had significantly higher 24-h mean levels of thyroxine than did males. No circadian rhythmicity was obvious for the plasma levels of any of the three hormones measured.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Hidrocortisona/sangre , Periodicidad , Tiroxina/sangre , Adrenalectomía , Animales , Ritmo Circadiano , Perros , Femenino , Luz , Masculino , Factores SexualesRESUMEN
Cortisol inhibits growth hormone (GH) release in short-term culture and is stimulatory in long-term cultures of rat and human pituitary cells. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-releasing hormone (GHRH)-stimulated GH release by at least 2 h. In short-term culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH release were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release caused by the calcium ionophore A23187 was unaffected. This suggests a possible action of cortisol on the calcium channels. The inhibition by cortisol of the calcium-dependent secretion of GH release appeared to play a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH release using puromycin, arachidonic acid or pertussis toxin were unsuccessful. Since cortisol inhibition of GH release does not occur via the mechanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a single inhibitory mechanism. The majority of cortisol actions on the somatotroph appear to act at a site distal to the production of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Hidrocortisona/farmacología , Hipófisis/metabolismo , Ovinos/fisiología , Animales , Ácido Araquidónico/farmacología , Bucladesina/farmacología , Calcimicina/farmacología , Células Cultivadas , Colforsina/farmacología , Depresión Química , Hormona del Crecimiento/análisis , Masculino , Toxina del Pertussis , Hipófisis/química , Hipófisis/citología , Hipófisis/efectos de los fármacos , Cloruro de Potasio/farmacología , Puromicina/farmacología , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (IL-1ra) would: first, increase food intake; secondly, decrease concentrations of GH; thirdly, reduce GHRH-induced release of GH; and fourthly, reduce changes to concentrations of IGF-I in plasma during experimental endotoxemia in sheep. Six treatments were given to six castrated male sheep in a 6x6 Latin square treatment order. Osmotic mini-pumps were implanted at 0 h and a jugular vein was cannulated. Each sheep was continuously infused with saline (0.9%) or lipopolysaccharide (LPS) (20 micrograms/kg per 24 h, s.c.) at 10 microliters/h for 72 h via the osmotic mini-pumps. Blood samples (3 ml) were collected at 15-min intervals from 24 to 33 h. At 26 h, one of three treatments (artificial cerebrospinal fluid, NPY or IL-1ra) was injected i.c.v. within 30 s (0.3 microgram/kg), then infused i.c.v. from 26 to 33 h (600 microliters/h) at 0.3 microgram/kg per h. GHRH was injected i.v. (0.075 microgram/kg) at 32 h after which blood samples were collected at 5, 10, 15, 30, 45 and 60 min. Feed intake was reduced up to 50% for 48 h in LPS-treated compared with non-LPS-treated sheep. NPY restored feed intake in LPS-treated sheep and induced hyperphagia in non-LPS-treated sheep from 24 to 48 h. In contrast, IL-1ra did not affect appetite. Injection of NPY increased concentrations of GH from 26 to 27 h, while IL-1ra had no effect. Infusion of NPY suppressed GHRH-induced release of GH. However, no treatment altered pulse secretion parameters of GH. Concentrations of IGF-I were 20% higher at 72 h in LPS-treated sheep given NPY than in sheep treated with LPS alone, and this may reflect increased appetite from 24 to 48 h. We concluded that reduced appetite during endotoxemia is due to down-regulation of an NPY-mediated mechanism. Furthermore, NPY stimulates release of GH in healthy sheep, does not reduce pulse secretion parameters of GH, but does suppress GHRH-induced release of GH in endotoxic sheep. Therefore, NPY may be an important neurotransmitter linking appetite with regulation of GH during endotoxemic and healthy states in sheep.
Asunto(s)
Estimulantes del Apetito/farmacología , Apetito/efectos de los fármacos , Endotoxemia/fisiopatología , Hormona del Crecimiento/sangre , Neuropéptido Y/farmacología , Animales , Temperatura Corporal , Ingestión de Alimentos/efectos de los fármacos , Endotoxemia/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Lipopolisacáridos , Masculino , Receptores de Interleucina-1/antagonistas & inhibidores , Proteínas Recombinantes/farmacología , OvinosRESUMEN
High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.
Asunto(s)
Enfermedades de los Bovinos/tratamiento farmacológico , Endotoxemia/veterinaria , Estradiol/uso terapéutico , Progesterona/uso terapéutico , Animales , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Bovinos , Enfermedades de los Bovinos/metabolismo , Implantes de Medicamentos , Quimioterapia Combinada , Ingestión de Alimentos/efectos de los fármacos , Endotoxemia/tratamiento farmacológico , Endotoxemia/metabolismo , Ácidos Grasos no Esterificados/sangre , Fiebre/tratamiento farmacológico , Fiebre/metabolismo , Hormona del Crecimiento/sangre , Hidrocortisona/sangre , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Análisis de los Mínimos Cuadrados , Masculino , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The interaction of arginine vasotocin (AVT) and norepinephrine (NE) upon pineal gland indoleamine synthesis was investigated. Rat pineal glands were incubated for 10 h in Krebs--Ringer bicarbonate plus 2 mg/ml glucose, 1 mg/ml bovine serum albumin, [14C]tryptophan, NE (10(-6) M), and log doses of AVT ranging from 100 ng to 10 microgram. Incubation media were extracted for [14C]serotonin while the other [14C]indoleamines, melatonin, hydroxyindoleacetic acid (HIAA), methoxyindoleacetic acid (MIAA), N-acetylserotonin (NAS), hydroxytryptophol (HTOL), and methoxytryptophol (MTOH) were separated by thin-layer chromatography. Serotonin metabolism was decreased by 0.1 microgram AVT and NAS decreased by 1.0 microgram AVT. Melatonin synthesis was decreased by both 0.1 and 1.0 microgram AVT. AVT also decreased the conversion of [14C]serotonin to MIAA and to HTOL. The data indicates that AVT decreased NE-stimulated pineal indoleamine synthesis in vitro and further suggests that AVT may participate in the intracellular regulation of melatonin synthesis.
Asunto(s)
Aminas Biogénicas/biosíntesis , Norepinefrina/farmacología , Glándula Pineal/metabolismo , Vasotocina/farmacología , Animales , Masculino , Melatonina/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Glándula Pineal/efectos de los fármacos , Ratas , Serotonina/biosíntesis , Triptófano/metabolismoRESUMEN
Nineteen canine mammary lesions were analyzed for estrogen receptor (ER), progesterone receptor (PR) and luteinizing hormone releasing hormone receptor (LHRHR) content. In addition, nine previously established canine mammary tumor cell lines with known ER and PR were analyzed for LHRHR. The incidence of receptors in the mammary tumor lesions was 21% for LHRHR, 10% for ER and 30% for PR. Statistical correlation was not observed between receptor status and diagnosis of malignant, benign, or hyperplastic lesions. A relationship between LHRHR and ER and PR content of canine mammary lesions or cell lines was not evident. The presence of functional hormone receptors offers opportunity for hormonal treatment of mammary cancer which may not be completely treatable by surgery. The observation of LHRHR in canine mammary tumors may offer therapeutic interventions other than surgery for mammary tumors unresponsive to antiestrogens.