RESUMO
To determine risk factors for running injuries during the Lage Landen Marathon Eindhoven 2012. Prospective cohort study. Population-based study. This study included 943 runners. Running injuries after the Lage Landen Marathon. Sociodemographic and training-related factors as well as lifestyle factors were considered as potential risk factors and assessed in a questionnaire 1 month before the running event. The association between potential risk factors and injuries was determined, per running distance separately, using univariate and multivariate logistic regression analysis. In total, 154 respondents sustained a running injury. Among the marathon runners, in the univariate model, body mass index ≥ 26 kg/m(2), ≤ 5 years of running experience, and often performing interval training, were significantly associated with running injuries, whereas in the multivariate model only ≤ 5 years of running experience and not performing interval training on a regular basis were significantly associated with running injuries. Among marathon runners, no multivariate model could be created because of the low number of injuries and participants. This study indicates that interval training on a regular basis may be recommended to marathon runners to reduce the risk of injury.
Assuntos
Traumatismos em Atletas/prevenção & controle , Extremidade Inferior/lesões , Condicionamento Físico Humano/métodos , Corrida/lesões , Adulto , Traumatismos em Atletas/epidemiologia , Índice de Massa Corporal , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Países Baixos , Condicionamento Físico Humano/estatística & dados numéricos , Estudos Prospectivos , Fatores de Risco , Corrida/estatística & dados numéricos , Adulto JovemRESUMO
Physiological and perceptual effects of wind cooling are often intertwined and have scarcely been studied in self-paced exercise. Therefore, we aimed to investigate (1) the independent perceptual effect of wind cooling and its impact on performance and (2) the responses to temporary wind cooling during self-paced exercise. Ten male subjects completed four trials involving 15 min standardized incremental intensity cycling, followed by a 15-km self-paced cycling time trial. Three trials were performed in different climates inducing equivalent thermal strain: hot humid with wind (WIND) and warm humid (HUMID) and hot dry (DRY) without wind. The fourth trial (W3-12) was equal to HUMID, except that wind cooling was unexpectedly provided during kilometers 3-12. Physiological, perceptual and performance parameters were measured. Subjects felt generally cooler during the WIND than the HUMID and DRY trials, despite similar heart rate, rectal and skin temperatures and a WBGT of ~4 °C higher. The cooler thermal sensation was not reflected in differences in thermal comfort or performance. Comparing W3-12 to HUMID, skin temperature was 1.47 ± 0.43 °C lower during the wind interval, leading to more favorable ratings of perceived exertion, thermal sensation and thermal comfort. Overall, power output was higher in the W3-12 than the HUMID-trial (256 ± 29 vs. 246 ± 22 W), leading to a 67 ± 48 s faster finish time. In conclusion, during self-paced exercise in the heat, wind provides immediate and constant benefits in physiological strain, thermal perception and performance. Independent of physiological changes, wind still provides a greater sensation of coolness, but does not impact thermal comfort or performance.
Assuntos
Desempenho Atlético/fisiologia , Exercício Físico/fisiologia , Percepção , Sensação Térmica , Vento , Adulto , Humanos , Umidade , Masculino , Limiar Sensorial , Temperatura Cutânea , TemperaturaRESUMO
INTRODUCTION: Both mean power output (MPO) and the distribution of the available energy over the race, that is, pacing strategy, are critical factors in performance. The purpose of this study was to determine the relative importance of both pacing strategy and MPO to performance. METHODS: Six well-trained, regionally competitive cyclists performed four 1500-m ergometer time trials (â¼2 min). For each subject, the fastest (Fast) and slowest (Slow) time trials were compared and the relative importance of differences in power output and pacing strategy were determined with an energy flow model. RESULTS: The difference in final time between Fast and Slow was 4.0 (2.5) s. Fast was performed with a higher MPO (437.8 (32.3) W vs 411.3 (39.0) W), a higher aerobic peak power (295.3 (36.8) vs 287.5 (34.7) W) and a higher anaerobic peak power (828.8 (145.4) W vs 649.5 (112.2) W) combined with a relatively higher, but not statistically different anaerobic rate constant (0.051 (0.016) vs 0.041 (0.009) W). The changes in MPO (63% anaerobic, 37% aerobic) largely explained the differences in final times. Athletes chose a different pacing strategy that was close to optimal for their physiological condition in both Fast and Slow. CONCLUSION: Differences in intraindividual performance were mainly caused by differences in MPO. Athletes seemed to be able to effectively adjust their pacing profile based on their "status of the day". Keywords modelling performance, energy expenditure, aerobic, anaerobic, sports.
Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Exercício Físico/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Metabolismo Energético/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Fatores de TempoRESUMO
There is little standardization of how to measure cycling gross efficiency (GE). Therefore, the purposes of these studies were to evaluate the effect of: i) stage duration, ii) relative exercise intensity, iii) work capacity and iv) a prior maximal incremental test on GE. Trained subjects (n=28) performed incremental tests with stage durations of 1-, 3-, and 6-min to establish the effect of stage duration and relative exercise intensity on GE. The effect of work capacity was evaluated by correlating GE with peak power output (PPO). In different subjects (n=9), GE was measured at 50% PPO with and without a prior maximal incremental test. GE was similar in 3- and 6-min stages (19.7 ± 2.8% and 19.3 ± 2.0%), but significantly higher during 1-min stages (21.1 ± 2.7%), GE increased with relative exercise intensity, up to 50% PPO or the power output corresponding to the ventilatory threshold and then remained stable. No relationship between work capacity and GE was found. Prior maximal exercise had a small effect on GE measures; GE was lower after maximal exercise. In conclusion, GE can be determined robustly so long as steady state exercise is performed and RER ≤ 1.0.
Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Tolerância ao Exercício/fisiologia , Adolescente , Adulto , Criança , Teste de Esforço , Feminino , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
Gonadotrophin surge-inhibiting/attenuating factor (GnSIF/AF) has been known for over two decades, but its molecular structure has not been completely characterized yet. In the last 20 years, five different putative GnSIF/AF sequences have been published. In this article, we describe a procedure to isolate and characterize GnSIF/AF from bovine follicular fluid, a GnSIF/AF-derived synthetic peptide (SP-GnSIF/AF) was produced, and the intracellular bioactivity of GnSIF/AF was tested for intracellular action with a MAPK-assay. Two different bioactive molecular weight forms of GnSIF/AF were isolated, a 160 kDa heteromeric and a monomeric 40 kDa protein. The 40 kDa form appeared to be a subunit of the 160 kDa protein. The synthetic peptide mimicked the actions of GnSIF/AF, such as inhibition of GnRH-induced LH secretion and attenuation of the MAPK phosphorylation. The two GnSIF/AF candidates do not show similarities with previously published GnSIF/AF sequences. These are the first data showing the influence of GnSIF/AF on intracellular processes involved in GnRH self-priming and that the biological action of GnSIF/AF was preserved in the produced synthetic peptide. The results provide strong evidence that the identified candidate proteins are the true GnSIF/AF.
Assuntos
Hormônios Gonadais , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/análise , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas , Animais , Bovinos , Feminino , Líquido Folicular/química , Hormônios Gonadais/síntese química , Hormônios Gonadais/isolamento & purificação , Hormônios Gonadais/fisiologia , Hormônio Luteinizante/análise , Hormônio Luteinizante/antagonistas & inibidores , Hormônio Luteinizante/metabolismo , Camundongos , Peso Molecular , Proteínas/síntese química , Proteínas/isolamento & purificação , Proteínas/fisiologia , Ratos , Ratos WistarRESUMO
PURPOSE: Athletes are trained to choose the pace which is perceived to be correct during a specific effort, such as the 1500-m speed skating competition. The purpose of the present study was to "override" self-paced (SP) performance by instructing athletes to execute a theoretically optimal pacing profile. METHODS: Seven national-level speed-skaters performed a SP 1500-m which was analysed by obtaining velocity (every 100 m) and body position (every 200 m) with video to calculate total mechanical power output. Together with gross efficiency and aerobic kinetics, obtained in separate trials, data were used to calculate aerobic and anaerobic power output profiles. An energy flow model was applied to SP, simulating a range of pacing strategies, and a theoretically optimal pacing profile was imposed in a second race (IM). RESULTS: Final time for IM was â¼2 s slower than SP. Total power distribution per lap differed, with a higher power over the first 300 m for IM (637.0 (49.4) vs 612.5 (50.0) W). Anaerobic parameters did not differ. The faster first lap resulted in a higher aerodynamic drag coefficient and perhaps a less effective push-off. CONCLUSION: Experienced athletes have a well-developed performance template, and changing pacing strategy towards a theoretically optimal fast start protocol had negative consequences on speed-skating technique and did not result in better performance.
Assuntos
Desempenho Atlético/fisiologia , Patinação/fisiologia , Metabolismo Energético/fisiologia , Fricção , Humanos , Modelos Biológicos , Consumo de Oxigênio/fisiologia , Adulto JovemRESUMO
Anaerobic capacity (AnC) can be estimated by subtracting VO (2) consumed from VO (2) demand, which can be estimated from multiple submaximal exercise bouts or by gross efficiency (GE), requiring one submaximal bout. This study compares AnC using the MAOD and GE method. The precision of estimated VO (2) demand and AnC, determined by MAOD using 3 power output - VO (2) regressions, based on VO (2) from min 8-10 (10 - Y), during min 4 without (4 - Y) and with forced y-intercept (4+Y), and from GE was evaluated by the 95% confidence interval (CI). Well-trained males (n=15) performed submaximal exercise tests to establish VO (2) demand with the MAOD and GE method. To determine AnC subjects completed a constant power output trial. The 3 MAOD procedures and GE method had no significant difference for VO (2) demand and AnC. The 4+Y MAOD procedure and GE method resulted in a smaller 95% CI of VO (2) demand and AnC than the 10 - Y ( P<0.05; P<0.01) and 4 - Y ( P<0.001; P<0.01) MAOD procedures. Therefore, the 4+Y MAOD procedure and GE method are preferred for estimating AnC, but as individual differences exist, they cannot be used interchangeably.
Assuntos
Limiar Anaeróbio/fisiologia , Ciclismo/fisiologia , Consumo de Oxigênio/fisiologia , Adulto , Desempenho Atlético , Teste de Esforço , Humanos , Masculino , Adulto JovemRESUMO
Severe congenital neutropenia (SCN) is a heterogeneous condition characterized by a drastic reduction in circulating neutrophils and a maturation arrest of myeloid progenitor cells in the bone marrow. Usually this condition can be successfully treated with granulocyte colony-stimulating factor (G-CSF). Here we describe the identification of a novel point mutation in the extracellular domain of the G-CSF receptor (G-CSF-R) in an SCN patient who failed to respond to G-CSF treatment. When this mutant G-CSF-R was expressed in myeloid cells, it was defective in both proliferation and survival signaling. This correlated with diminished activation of the receptor complex as determined by signal transducer and activator of transcription (STAT) activation, although activation of STAT5 was more affected than STAT3. Interestingly, the mutant receptor showed normal affinity for ligand, but a reduced number of ligand binding sites compared with the wild-type receptor. This suggests that the mutation in the extracellular domain affects ligand-receptor complex formation with severe consequences for intracellular signal transduction. Together these data add to our understanding of the mechanisms of cytokine receptor signaling, emphasize the role of GCSFR mutations in the etiology of SCN, and implicate such mutations in G-CSF hyporesponsiveness.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/congênito , Neutropenia/tratamento farmacológico , Mutação Puntual , Receptores de Fator Estimulador de Colônias de Granulócitos/genética , Células da Medula Óssea/metabolismo , Divisão Celular , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Lactente , Ligantes , Modelos Moleculares , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Transdução de SinaisRESUMO
Although several familial cancer genes with high-penetrance mutations have been identified, the major genetic component of susceptibility to sporadic cancers is attributable to low-penetrance alleles. These 'weak' tumor susceptibility genes do not segregate as single Mendelian traits and are therefore difficult to find in studies of human populations. Previously, we have proposed that a combination of germline mapping and analysis of allele-specific imbalance in tumors may be used to refine the locations of susceptibility genes using mouse models of cancer. Here, we have used linkage analysis and congenic mouse strains to map the major skin tumor susceptibility locus Skts1 within a genetic interval of 0.9 cM on proximal chromosome 7. This interval lies in an apparent recombination cold spot, and corresponds to a physical distance of about 15 Mb. We therefore, used patterns of allele-specific imbalances in tumors from backcross and congenic mice to refine the location of Skts1. We demonstrate that this single tumor modifier locus has a dramatic effect on the allelic preference for imbalance on chromosome 7, with at least 90% of tumors from the congenics showing preferential gain of markers on the chromosome carrying the susceptibility variant. Importantly, these alterations enabled us to refine the location of Skts1 at higher resolution than that attained using the congenic mice. We conclude that low-penetrance susceptibility genes can have strong effects on patterns of allele-specific somatic genetic changes in tumors, and that analysis of the directionality of these somatic events provides an important and rapid route to identification of germline genetic variants that confer increased cancer risk.
Assuntos
Alelos , Predisposição Genética para Doença , Neoplasias Cutâneas/genética , Animais , Linhagem Celular , Hibridização in Situ FluorescenteRESUMO
This paper demonstrates the development of indirect potable reuse (IPR) in the United States. A legislative review and a survey of plants show that IPR is becoming an integral part of water reclamation. Public resistance is the limiting factor to its development while technology is not.
Assuntos
Conservação dos Recursos Naturais , Eliminação de Resíduos Líquidos , Abastecimento de Água , Conservação dos Recursos Naturais/legislação & jurisprudência , Conservação dos Recursos Naturais/tendências , Estados Unidos , Purificação da Água/métodosRESUMO
A 73-year old man underwent a segmental liver resection for a solitary liver metastasis from a rectal carcinoma. On post-operative day one, an accidental potassium chloride infusion (total 29 mmol or 1135 mg of KCl) was given via the epidural catheter. Within a few hours this resulted in pruritus, progressive muscle spasms, decreased consciousness and vegetative symptoms such as tachycardia and hypertension. Subsequently respiratory insufficiency developed, necessitating intubation and ventilation of the patient with admission to the Intensive Care Unit. The patient received a single dose of 40 mg of dexamethasone intravenously to prevent or decrease possible myelum edema, and 100 ml x h(-1) of NaCl 0.9% infusion over the epidural catheter for several hours. The patient made a complete recovery, was extubated successfully six hours after ICU-admission and discharged home free of symptoms.
Assuntos
Anestesia Epidural , Erros Médicos , Cloreto de Potássio/efeitos adversos , Idoso , Dexametasona/uso terapêutico , Humanos , Masculino , Cloreto de Potássio/administração & dosagemRESUMO
The development of cancer is influenced both by exposure to environmental carcinogens and by the host genetic background. Epistatic interactions between genes are important in determining phenotype in plant and animal systems and are likely to be major contributors to cancer susceptibility in humans. Several tumor modifier loci have been identified from studies of mouse models of human cancer, and genetic interactions between modifier loci have been detected by genome scanning using recombinant congenic strains of mice (R. Fijneman et al., Nat. Genet., 14: 465-467, 1996; T. van Wezel et al., Nat. Genet., 14: 468-470, 1996; W. N. Frankel et al., Nat. Genet., 14, 371-373, 1996). We demonstrate here that strong genetic interactions between skin tumor modifier loci can be detected by hierarchical whole genome scanning of a complete interspecific backcross [outbred Mus spretus X Mus musculus (NIH/Ola)]. A locus on chromosome 7 (Skts1) showed a highly significant interaction with Skts5 on chromosome 12 (P < 10(-16)), whereas additional significant interactions were detected between loci on chromosomes 4 and 5, and 16 and 15. Some of these quantitative trait loci and their interactions, in particular the Skts1-Skts5 interaction, were confirmed in two completely independent backcrosses using inbred spretus strains (SEG/Pas and SPRET/Ei) and NIH/Ola. These results, therefore, illustrate the general use of interspecific crosses between Mus musculus and Mus spretus for the detection of strong genetic interactions between tumor modifier genes.
Assuntos
Epistasia Genética , Neoplasias Cutâneas/genética , Animais , Feminino , Ligação Genética , Predisposição Genética para Doença , Endogamia , Masculino , Camundongos , Papiloma/genéticaRESUMO
The signal transducer and activator of transcription (STAT) proteins have been implicated in cytokine-regulated proliferation, differentiation and cell survival. Granulocyte colony-stimulating factor (G-CSF), a regulator of granulocytic differentiation, induces a robust and sustained activation of STAT3. Here, we show that introduction of dominant negative (DN) forms of STAT3 interferes with G-CSF-induced differentiation and survival in murine 32D cells. G-CSF induces expression of the cyclin-dependent kinase (cdk) inhibitor p27(KiP1) (but not p21(CiP1)), which is completely blocked by DN-STAT3. The ability of tyrosine-to-phenylalanine substitution mutants of the G-CSF receptor to activate STAT3 strongly correlated with their capacity to induce p27 expression and their ability to mediate differentiation and survival, suggesting a causal relationship between STAT3 activation, p27 expression and the observed cellular responses. We identified a putative STAT binding site in the promoter region of p27 that showed both STAT3 binding in electrophoretic mobility shift assays and functional activity in luciferase reporter assays. Finally, we studied G-CSF-induced responses in primary bone marrow and spleen cells of p27-deficient mice. Compared with wild-type, myeloid progenitors from p27-deficient mice showed significantly increased proliferation and reduced differentiation in response to G-CSF. These findings indicate that STAT3 controls myeloid differentiation, at least partly, via upregulation of p27(Kip1).
Assuntos
Proteínas de Ciclo Celular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Inibidores Enzimáticos , Fator Estimulador de Colônias de Granulócitos/metabolismo , Proteínas Associadas aos Microtúbulos/fisiologia , Transativadores/metabolismo , Proteínas Supressoras de Tumor , Animais , Sítios de Ligação , Diferenciação Celular , Divisão Celular , Sobrevivência Celular , Inibidor de Quinase Dependente de Ciclina p27 , Proteínas de Ligação a DNA/genética , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/genética , Células HeLa , Humanos , Ligantes , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Mutagênese , Neutrófilos/citologia , Regiões Promotoras Genéticas , Fator de Transcrição STAT3 , Células-Tronco/citologia , Transativadores/genética , Transfecção , Células Tumorais CultivadasRESUMO
Anatomical and functional studies show that the hypothalamus is at the junction of mechanisms involved in the exploratory appraisal phase of behaviour and mechanisms involved in the execution of specific consummatory acts. However, the hypothalamus is also a crucial link in endocrine regulation. In natural settings it has been shown that behavioural challenges produce large and fast increases in circulating hormones such as testosterone, prolactin, corticotropin and corticosterone. The behavioural function and neural mechanisms of such fast neuroendocrine changes are not well understood. We suggest that behaviourally specific hypothalamic mechanisms, at the cross-roads of behavioural and endocrine regulation, play a role in such neuroendocrine changes. Mild stimulation of the hypothalamic aggressive area, produces stress levels of circulating prolactin, corticotropin, and corticosterone. Surprisingly luteinizing hormone does not change. This increase in stress hormones is due to the stimulation itself, and not caused by the stress of fighting. Similar increases in corticosterone are observed during electrical stimulation of the hypothalamic self-grooming area. The corticosterone response during self-grooming-evoking stimulation is negatively correlated with the amount of self-grooming observed, suggesting that circulating corticosterone exerts a negative feedback control on grooming. Earlier literature, and preliminary data form our laboratory, show that circulating corticosterone exerts a fast positive feedback control over brain mechanisms involved in aggressive behaviour. Such findings suggest that the hormonal responses caused by the activity of behaviourally specific areas of the hypothalamus may be part of a regulation mechanism involved in facilitating or inhibiting the very behavioural responses that can be evoked from those areas. We suggest that studying such mechanisms may provide a new approach to behavioural dysfunctions associated with endocrine disorders and stress.
Assuntos
Agressão/fisiologia , Agressão/psicologia , Comportamento Animal/fisiologia , Glândulas Endócrinas/fisiologia , Asseio Animal/fisiologia , Hipotálamo/fisiologia , AnimaisRESUMO
The terminals of the hypothalamic gonadotrophin hormone-releasing hormone (GnRH) neurons are located within the median eminence and thereby extend beyond the protection of the blood-brain barrier. Thus, these terminals may be subjected to direct autoimmune action in animals that are actively immunised against GnRH. Boars (male pigs) (n = 108) were actively immunised against GnRH by two successive injections with synthetic GnRH, covalently coupled to KLH and dissolved in CFA or IFA. They were killed at 26 weeks of age. Immunised boars were selected on the basis of the resultant testes size, which indicates the effectiveness of the immunisation. The hypothalami of 25 selected animals were studied by histological and immunocytochemical techniques and compared with the hypothalami of three sham- and nine control animals. In the immunised animals, changes in the GnRH system had taken place. These comprised dystrophy of the perikarya and a sharp decrease of the GnRH immunocytochemical reactivity in the terminals within the median eminence. In addition, various degrees of inflammatory reactions were present, particularly within the median eminence. These consisted of tissue disruption by edema, collapse of the capillaries, fibrosis and infiltration with fibroblasts. In addition, accumulations of neurosecretum within the median eminence in combination with hypertrophy of magnocellular neurons within the hypothalamus were present. The reactions were restricted to the median eminence and did not involve other neurohemal organs or other parts of the hypothalamus. A correlation could be established between the incidence of the lesions and the effectiveness of the GnRH autoimmunity (as indicated by the size and endocrine function of the gonads and the anti-GnRH titres). Changes in extra- and intracellular IgG immunocytochemical reactivity within the median eminence indicated the involvement of IgG. The effects were absent from control and sham vaccinated animals and after vaccinations with other compositions of the vaccine. Thus, hypothalamic lesions have been observed in this selected group of animals, vaccinated against GnRH with this particular vaccine.
Assuntos
Autoanticorpos/imunologia , Hormônio Liberador de Gonadotropina/imunologia , Eminência Mediana/patologia , Sequência de Aminoácidos , Animais , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/imunologia , Hormônio Liberador de Gonadotropina/análise , Imunoglobulina G/imunologia , Masculino , Eminência Mediana/imunologia , Dados de Sequência Molecular , Suínos , VacinaçãoRESUMO
The refractoriness of LH release by pituitary glands from intact female rats was studied during stimulation by luteinizing hormone releasing hormone (LH-RH), monobutyryl cyclic AMP+theophylline or potassium in vitro. Various concentrations of LH-RH (0.1, 0.3 and 10 ng/ml) all caused refractoriness within 24 h. Subsequent exposure to a supramaximally active concentration of LH-RH for 6 h also resulted in a depressed response; the degree of inhibition depended on the concentration of LH-RH to which the glands had been exposed previously. Glands made refractory to LH-RH also showed a depressed response to monobutyryl cyclic AMP+theophylline, although these agents by themselves were unable to induce refractoriness. Incubation in medium containing a high concentration of potassium also resulted in the release of LH, which in all respects was similar to that caused by LH-RH. Glands made refractory to LH-RH showed a decreased response to potassium and, conversely, the release of LH in response to LH-RH was reduced after exposure of glands to potassium. It is concluded that the LH releasing activity of LH-RH, which is mimicked by potassium, deteriorates during continuous exposure to the secretagogue.
Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Hipófise/fisiologia , Animais , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Depressão Química , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Técnicas In Vitro , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Potássio/farmacologia , Ratos , Teofilina/farmacologia , Fatores de TempoRESUMO
When pituitary glands from intact female rats are incubated with LHRH, the resulting LH release shows a biphasic pattern: an initial low rate of LH release (lag phase) is followed by a high rate. When pituitary glands from long-term ovariectomized rats are incubated, the rate of LH release is high throughout stimulation with LHRH. The disappearance of the lag phase might be due to increased LHRH release after ovariectomy and/or the disappearance of ovarian factors. To distinguish between these possibilities, pituitary glands which had been exposed to endogenous LHRH (pituitary glands in situ) or which had been unexposed to endogenous LHRH (pituitary glands transplanted under the kidney capsule) were incubated in the presence or absence of LHRH. Biphasic LH secretion patterns were observed during incubation with LHRH with the animal's own pituitary gland and with the transplanted pituitary gland from intact, but not from ovariectomized rats. Thus the disappearance of the lag phase after ovariectomy results from the absence of ovarian secretory products, rather than from increased release of LHRH.
Assuntos
Hormônio Liberador de Gonadotropina/fisiologia , Hormônio Luteinizante/metabolismo , Ovário/fisiologia , Hipófise/fisiologia , Animais , Bromocriptina/farmacologia , Feminino , Hormônio Luteinizante/sangue , Ovariectomia , Hipófise/efeitos dos fármacos , Hipófise/transplante , Prolactina/sangue , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The effects of discontinuation and restoration of ovarian influences on the pituitary LH response to LHRH in vitro were investigated. When female rat pituitary glands taken on day 2 of dioestrus were incubated with LHRH the release of LH was low during the first hour (lag phase response) and afterwards a progressive, protein synthesis-dependent increase took place (second phase response), this being the self-priming action of LHRH. Short-term discontinuation (less than 1 day) of ovarian influences on the rat pituitary gland in vivo (ovariectomy) or in vitro (incubation in medium only) resulted in an increased LHRH-induced LH response during the lag phase. The biphasic LH response or the self-priming action of LHRH disappeared completely after long-term discontinuation of ovarian influences on the pituitary gland, LH release being at its maximum from the start of the incubation. The biphasic response was reinstated when ovaries were implanted under the kidney capsules of ovariectomized rats. Auto-implantation of an ovary into the spleen immediately after bilateral ovariectomy did not, however, prevent the disappearance of the LHRH self-priming action. Ovarian activity responsible for the presence of the low LH response during the lag phase was thus effectively removed by the liver, but inhibin-like activity suppressing serum FSH levels remained present. Silicone elastomer implants (s.c.) containing oestradiol-17 beta, implanted for 4 weeks, did not reverse the loss of the biphasic LH response to LHRH. It is concluded that liver-labile factors released by the ovaries keep the pituitary gland in a state of low responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Ovário/fisiologia , Hipófise/metabolismo , Animais , Diestro , Feminino , Técnicas In Vitro , Ovariectomia , Ovário/transplante , Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Pituitary glands taken from intact rats on day 2 of dioestrus and incubated with LHRH show a biphasic pattern of LH and FSH release. Initially the release of the gonadotrophins is low (first-phase or lag-phase response), but increases during further incubation with LHRH (second-phase or primed-state response). Removal of the influence of an unidentified ovarian factor either by ovariectomy or prolonged incubation in medium only leads to an increased (lag-phase) response to LHRH. The development of the increased response after prolonged incubation was prevented by the addition of cycloheximide to the media, implicating that this process is dependent upon the synthesis of protein. Steroid-free material (bovine follicular fluid or rat ovarian extracts) prevented the development of this process. In addition, it was shown that steroid-free rat ovarian extracts were also able to induce the development of a lag phase in pituitary glands from ovariectomized rats. Finally, it was found that steroid-free ovarian extracts reversed the self-priming effect of LHRH. The biological activity which reduced the responsiveness of the pituitary gland towards stimulation by LHRH was eliminated after the use of protein-denaturating techniques such as increased temperature or addition of methanol. The presence of this activity in ovaries, did not vary during the oestrous cycle, contrary to inhibin-like activity. Hence the ovarian factor responsible for the low lag-phase response is a protein which is probably not identical to inhibin. It is concluded that a non-steroidal ovarian factor reduces the responsiveness of the anterior pituitary gland to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/fisiologia , Hormônio Luteinizante/metabolismo , Ovário/fisiologia , Adeno-Hipófise/fisiologia , Extratos de Tecidos/farmacologia , Animais , Cicloeximida/farmacologia , Feminino , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
When pituitary glands from intact female, but not from ovariectomized rats, are incubated for 8 h in medium TC199 without further additives, FSH is synthesized. This LHRH-independent (or autonomous) FSH synthesis is prevented when bovine follicular fluid (bFF) is added to the incubation medium. Results from preliminary experiments, however, indicate no clear autonomous FSH synthesis after long-term absence of LHRH. To investigate the regulatory mechanisms involved in autonomous FSH synthesis and release, pituitary glands (exposed to endogenous LHRH) and pituitary grafts (not exposed to endogenous LHRH) from intact and ovariectomized rats were incubated for 8 h in medium TC199. Total FSH content (FSH released plus FSH remaining in the tissue) was compared with that in non-incubated glands or grafts, giving an indication of FSH synthesis. In addition, some of the animals were given LHRH pulses for 40 h before incubation. When pituitary tissue was taken from intact female rats, FSH synthesis occurred in the animals' own glands and in grafts from LHRH-pretreated rats. No FSH synthesis was seen in ovariectomized rats with or without pretreatment with bFF and/or LHRH. However, when ovariectomized rats had been pretreated with oestrogen, FSH synthesis was measured in vitro after pulsatile LHRH treatment in vivo. The results indicate that autonomous FSH synthesis in vitro is dependent upon previous (in vivo) exposure of the glands to both oestrogen and LHRH.