RESUMO
It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normal-weighted subjects. A progressive decline in serum cortisol levels occurred in obese patients after RMET, while an opposite pattern (i. e., a significant cortisol increase) was found in normal-weighted subjects. Optimization of long-term RMET protocols could represent a valid strategy to (physiologically) stimulate GH/IGF-I system in those GH hyposecretory states such as obesity.
Assuntos
Exercícios Respiratórios , Hormônio do Crescimento Humano/sangue , Hidrocortisona/sangue , Obesidade Mórbida/sangue , Resistência Física , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: The abrupt fall in estrogens levels during the menopausal transition may connote an hormonal state predisposing to neurodegenerative disorders, e.g. Alzheimer's disease (AD). Reportedly, the neurotrophic activity of estrogen involves an interaction with IGF-I. AIM: To evaluate the leukocyte gene expression of progesterone receptor (PR-A/B) and interleukin 6 (IL-6), two parameters under the control of estrogens and involved in the pathogenesis of AD. SUBJECTS: The study was conducted in non-demented women divided into two groups according to their pre- or post-menopausal state; each group being further divided into two subgroups based on their circulating levels of IGF-I (normal or low). An additional sample of AD-affected women served as a comparison group. RESULTS: Estrogens maintained their full activity only when IGF-I levels were in the range of normalcy. On the contrary, if the concentrations of one or both hormones were reduced, estrogens were not anymore capable to control the gene expression of PR-A/B or IL-6. CONCLUSIONS: Before administering hormone-based replacement therapy, characterization of the somatotropic function should be performed in the early phase of the menopause.
Assuntos
Estrogênios/uso terapêutico , Terapia de Reposição Hormonal/métodos , Fator de Crescimento Insulin-Like I/fisiologia , Doenças Neurodegenerativas/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Pós-Menopausa/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estrogênios/metabolismo , Estrogênios/fisiologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Pessoa de Meia-Idade , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/metabolismo , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Adulto JovemRESUMO
Repetition of voluntary exercise bouts and of different pharmacological GH-releasing stimuli at 2-h intervals is associated with a complete abolishment of GH responsiveness. By contrast, a different pattern is observed after repeated neuromuscular electrostimulation, which is characterized by preservation of GH responsiveness. Aim of the study was to evaluate GH responses to repeated bouts of respiratory muscle endurance training (RMET) by mean of a specific commercially available device (Spiro Tiger®). Eight healthy men underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH, cortisol and lactate (LA) determinations were collected during the 12th session, which was composed of two consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2 h interval. Baseline GH levels (mean: 0.9±0.4 ng/ml) significantly (p<0.01) increased after the first bout of RMET (peak: 15.7±4.0 ng/ml). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase (peak: 3.9±0.8 ng/ml) in comparison with the first one. Baseline LA levels (mean: 1.2±0.1 mmol/l) significantly increased (p<0.001) after the first bout of RMET (peak: 2.3±0.2 mmol/l). The administration of the second RMET bout resulted in a comparable LA increase (from a basal value of 1.2±0.1 mmol/l up to a peak of 2.0±0.1 mmol/l, p<0.001). The first bout of RMET caused a significant increase of cortisol levels (p<0.01), starting from a basal mean value of 142.9±9.4 ng/ml up to a peak of 188.8±10.3 ng/ml. By contrast, the second bout of RMET did not induce any significant change of cortisol levels (basal: 149.1±9.0 ng/ml, peak: 168.5±5.1 ng/ml). In conclusion, a single bout of RMET is capable of stimulating GH and cortisol secretions and LA production. When a second bout is repeated after 2 h, there is a blunting of GH and cortisol responses with a preservation of LA release. Further studies are needed to schedule long-term RMET protocols capable of persistently stimulating GH-IGF-I release and to maximally enhance the ergogenic and metabolic benefits of this intervention either in normal subjects (e.g. athletes) or patients with an impairment of motor capabilities requested to perform normal daily activities (i.e. severely obese and elderly people).
Assuntos
Exercícios Respiratórios , Hormônio do Crescimento Humano/sangue , Resistência Física/fisiologia , Músculos Respiratórios/fisiologia , Adulto , Equipamentos e Provisões , Exercício Físico/fisiologia , Saúde , Hormônio do Crescimento Humano/metabolismo , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Masculino , Músculos Respiratórios/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
To date, the large majority of studies evaluating growth hormone (GH) response to acute physical exercise has been performed involving gross muscle groups. To the best of our knowledge, none has evaluated the effects of a respiratory muscle endurance training (RMET) on hormonal secretions, particularly on GH release, though some respiratory devices have been widely used in athletes to train respiratory muscles and to improve cardiopulmonary function and physical performance. 8 healthy men underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, ghrelin, glucose, and lactate (LA) levels. GH and cortisol responses significantly increased after a 15-minute RMET session, which, in contrast, inhibited ghrelin secretion. There was a minimal, though significant, increase in LA levels with a significant elevation in glycemia. A 15-minute RMET session, administered after a 11-days incremental progressive RMET protocol, was capable of stimulating GH and cortisol release and suppressing ghrelin secretion. Optimization of incremental progressive RMET protocols would be important to maximize the positive chronic effects of this intervention on somatotropic function and muscle performance.
Assuntos
Exercícios Respiratórios , Hormônio do Crescimento Humano/metabolismo , Resistência Física , Adulto , Feminino , Grelina/sangue , Grelina/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Masculino , Músculos Respiratórios/fisiologia , Adulto JovemRESUMO
Human GH (hGH) is a heterogeneous protein hormone consisting of several isoforms. This heterogeneity is the consequence of multiple hGH genes, mRNA splicing, post-translational modifications, and peripheral metabolism, and it represents one important reason for the disparity among GH assay results from different laboratories. However, other factors are involved: a) interference from endogenous GH binding proteins; b) different specificities of anti- GH (monoclonal and polyclonal) antibodies; c) different matrix effects among the calibrators; d) the use of different calibrators. The measurement of GH levels in response to provocative testing is an essential part of the diagnosis of GH deficiency. For this purpose, an accurate, reproducible and universally valid GH measurement would be highly desirable, but, despite a huge number of efforts in clinical biochemistry, this goal remains elusive.
Assuntos
Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/sangue , Bioensaio , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/genética , Humanos , Família Multigênica , Isoformas de ProteínasRESUMO
Obese patients have decreased fasting and postprandial levels of peptide YY (PYY), an anorexigenic peptide produced by the L cells of the gastrointestinal mucosa. Fatty nutrients are the most powerful stimulus for PYY release. Cholestyramine, an anion exchanger which adsorbs bile salts, reduces digestion of lipids. The aim of the present study was to investigate the effects of cholestyramine or placebo on PYY secretion in obese women administered a high-fat meal [n=8; age: 30.9±2.7 years; BMI: 47.3±3.3 kg/m2]. Postprandial PYY levels in obese women given placebo significantly increased in plasma at 30, 60, 90, and 120 min after meal ingestion. Cholestyramine administration significantly reduced postprandial PYY response at 15, 30, and 60 min. Percent fat mass (FM%) was negatively correlated with the percent increment of plasma PYY concentrations induced by meal administration at 30 min; conversely, there was a positive correlation between FM% and the percent decrement of plasma PYY concentrations induced by cholestyramine at the same time interval. These correlations failed to reach statistical significance when related to BMI. This study implies that in the obese state the altered PYY response to food consumption is a consequence of a dysfunction of L cells, which become less sensitive to the positive feedback effect of lipids.
Assuntos
Adiposidade/efeitos dos fármacos , Resina de Colestiramina/farmacologia , Obesidade/sangue , Obesidade/fisiopatologia , Peptídeo YY/sangue , Período Pós-Prandial/efeitos dos fármacos , Adulto , Glicemia/metabolismo , Colesterol/sangue , Resina de Colestiramina/administração & dosagem , Gorduras na Dieta , Feminino , Humanos , Insulina/sangue , Triglicerídeos/sangueRESUMO
OBJECTIVE: To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise. DESIGN: Clinical longitudinal study on inpatients in a specialised institution. SUBJECTS: A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. MEASUREMENTS: The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. RESULTS: At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (p<0.05), without any significant fat-free mass loss (in % terms). In response to both meals and exercise, after the 3-week intervention, plasma leptin concentration decreased significantly (p<0.05), whereas the other hormones (insulin, ghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. CONCLUSION: This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.
Assuntos
Ingestão de Alimentos/fisiologia , Exercício Físico/fisiologia , Grelina/sangue , Leptina/sangue , Obesidade/terapia , Hormônios Peptídicos/sangue , Adolescente , Criança , Terapia Combinada/métodos , Feminino , Humanos , Comunicação Interdisciplinar , Masculino , Obesidade/sangue , Obesidade/metabolismo , Padrões de Referência , Redução de Peso/fisiologiaRESUMO
Acute exercise is a well-known stimulus for GH secretion but the effect of chronic training on GH secretion still remains equivocal. The aim of our study was to analyse spontaneous pulsatile GH secretion (during a period of 2 hours in the morning) in a group of young elite athletes (EA) compared with non-elite athletes (NEA), and sedentary subjects (SS). Mean and peak GH levels proved significantly higher in EA than in NEA and SS (p=0.0004 and p<0.0001, respectively). The same differences in mean and peak GH levels were also demonstrated in males and females when considered separately (males: p=0.0062 and p=0.0025; females: p=0.0056 and p=0.0032). In addition, GH levels (mean and peak) were higher in females than in males in SS while no differences were demonstrated between the 2 sexes in the EA and NEA groups. IGF-I levels were within the normal range for age in all the subjects with no difference between the 3 groups. Body mass index (BMI) exhibited no difference between groups, while EA showed higher lean mass (p=0.0063) and lower fat mass (p=0.0139) than NEA and SS measured by dual-energy x-ray absorptiometry. A strong positive correlation between GH levels (mean and peak) and hours of training a week was demonstrated (p=0.0101; r2=0.1184; p=0.0022; r2=0.1640, respectively). In conclusion, GH levels were higher in EA than NEA and SS without any modification of IGF-I levels; a strong positive correlation was present between GH levels and intensity of training. An increase in the knowledge of the effect of chronic training on GH secretion could improve the training programme to elicit the greatest exercise- induced GH response.
Assuntos
Exercício Físico/fisiologia , Hormônio do Crescimento Humano/metabolismo , Fluxo Pulsátil , Esportes/fisiologia , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Aptidão Física/fisiologia , Caracteres SexuaisRESUMO
AIM: The aim of this study was to evaluate growth hormone (GH) and ghrelin levels in response to physical exercise in athletes. METHODS: Two different exercise workloads were administered in two different groups of athletes. Group A athletes (19 males, 18 females; mean age +/- standard deviation: 25+/-6.7 years), performing a 60-90 min training session at approximately 80% of VO2max, were sampled for GH and ghrelin determinations before and immediately at the end of a training session on-the-field. Group B athletes (4 males; mean age: 28.2+/-7.2 years) performed two consecutive 30-min cycling sessions at 80% of individual VO2max at different time intervals between bouts (2 and 6 h) in two different days. GH and ghrelin concentrations were determined in blood samples collected at 15-min intervals during exercise and following 1 h of recovery. RESULTS: In group A athletes, GH levels increased after the training session (P<0.0001), with no differences between males and females. In male athletes, ghrelin levels significantly decreased after the training session (from 1 506.4+/-859 to 1 254.8+/-661.7 pg/mL, P<0.05), while no significant changes were found in females. No correlations were observed between GH and ghrelin levels at rest and after training. In group B athletes, GH levels significantly increased after the first exercise bouts (peak: 26.8+/-11.2 and 17.3+/-3.5 ng/mL, respectively), while the pattern of GH response was different after the second bout of exercise performed at 2-h or 6-h interval. In fact, peak GH concentration in response to the second bout (4.3+/-1.6 ng/mL) was lower (P<0.01) than that of the first bout when the interval elapsed was only 2 h, while a recovery of GH responsiveness was evident after the 6-h interval between the two exercise bouts (11.9+/-3.3 ng/mL). As far as ghrelin levels are concerned, no significant changes were observed during and after the two exercise bouts performed at the different time intervals. CONCLUSION: GH responses to prolonged exercise bouts (60-90 min) are associated with changes in ghrelin levels only in male athletes, while repeated exercise bouts of lower duration (30 min), capable to determine marked GH responses, are divorced from changes in ghrelin concentrations.
Assuntos
Desempenho Atlético , Exercício Físico/fisiologia , Grelina/sangue , Hormônio do Crescimento Humano/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aptidão Física , Estudos Prospectivos , Fatores Sexuais , Fatores de TempoRESUMO
Many studies have been prompted in the last few years aimed at clarifying and disentangle the different components involved in the control of metabolism and body weight. Based on a host of neuroanatomic, immunohistochemical and physiological findings, it is now clear that the hypothalamus is activated or deactivated by a series of afferent signals either hormonal or neural originated by peripheral tissues, which reflect changes in the global energy state. These hormonal and neural signals mainly stem from the adipose tissue, which is now considered a true endocrine organ, and, alternatively, by the gastrointestinal tract, in relation to fasting, feeding or refeeding conditions, and are vehicled to the brain where they act on receptors of an increasing family of first and second order peptides. This contribution at first presents the key elements of the complex mechanisms of control of metabolism and body weight, and then reports on recent presented advances in neuroendocrine and autonomic regulation of metabolic functions.
Assuntos
Tecido Adiposo/metabolismo , Regulação do Apetite/fisiologia , Sistema Nervoso Autônomo/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Metabolismo Energético/fisiologia , Sistemas Neurossecretores/metabolismo , Animais , Benzodiazepinas/farmacologia , Endocanabinoides , Hormônios Gastrointestinais/metabolismo , Grelina/fisiologia , Homeostase , Humanos , Fatores de Crescimento Neural/fisiologia , Sistemas Neurossecretores/fisiologia , Olanzapina , Ácidos Oleicos/farmacologia , Fragmentos de Peptídeos/fisiologia , Transdução de Sinais/fisiologiaRESUMO
Since Mycoplasma hyopneumoniae isolation in appropriate media is a difficult task and impractical for daily routine diagnostics, Nested-PCR (N-PCR) techniques are currently used to improve the direct diagnostic sensitivity of Swine Enzootic Pneumonia. In a first experiment, this paper describes a N-PCR technique optimization based on three variables: different sampling sites, sample transport media, and DNA extraction methods, using eight pigs. Based on the optimization results, a second experiment was conducted for testing validity using 40 animals. In conclusion, the obtained results of the N-PCR optimization and validation allow us to recommend this test as a routine monitoring diagnostic method for Mycoplasma hyopneumoniae infection in swine herds.
RESUMO
OBJECTIVE: Biallelic ablation of VGF determines a dwarf phenotype. VGF precursor protein encodes for different biologically active peptides none of which has been related to growth or muscular abnormalities. Here we present the first attempt to fill this gap. We tested the hypothesis that a recently identified VGF-derived peptide, TLQP-21, shown to centrally modulate metabolic functions, could also modulate growth hormone (GH)-axis and muscle strength. DESIGN: Adult male mice were chronically icv injected with TLQP-21 (15 microg/day for 14 days). Physiological, molecular and behavioral parameters related to the GH/IGF-1-axis were investigated. RESULTS: Except for a reduction in the soleus weight, TLQP-21 did not affect GH/IGF-1-axis mediators, muscle strength and muscle weight. CONCLUSIONS: Results collected exclude a role for TLQP-21 in modulating the GH/IGF1-axis and muscle functions. VGF-derived peptides involved in the dwarf phenotype of VGF-/- mice have to be identified yet.
Assuntos
Hormônio do Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Força Muscular/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Camundongos , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacosRESUMO
Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders. In ten, TRH, 500 microgram given intravenously, induced a rise in plasma growth hormone (GH) level, while in eight patients it induced a rise in plasma levels of FSH or LH or both. When LH-RH, 150 microgram was administered intravenously to ten patients, it induced a rise in plasma GH level in one patient and increased plasma prolactin level in three patients. Collectively, in only three of 14 patients was conventional AP responsiveness to hypothalamic neurohormones present. These findings demonstrate the existence of a profound derangement of AP responsiveness to hypothalamic neurohormones in depressed patients and suggest that a primary alteration in the physiologic links between the central nervous system and the AP may be at the origin of the neuroendocrine disturbance.
Assuntos
Transtorno Bipolar/fisiopatologia , Depressão/fisiopatologia , Hormônio Liberador de Gonadotropina/farmacologia , Adeno-Hipófise/fisiopatologia , Hormônio Liberador de Tireotropina/farmacologia , Adulto , Idoso , Transtorno Bipolar/sangue , Depressão/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio do Crescimento/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Adeno-Hipófise/efeitos dos fármacos , Prolactina/sangue , Tireotropina/sangueRESUMO
Intravenous administration of methoxamine ( METHOX , 5 mg, iv), a specific alpha 1-adrenergic agonist, reduced baseline GH levels of four unanesthetized beagle dogs 45 and 60 min post-injection and completely abolished the GH-releasing effect of the alpha 2-adrenergic agonist clonidine ( CLON , 4/ micrograms/kg, iv). Prazosin (PRA, 0.1 mg/kg, iv), an alpha 1-adrenergic antagonist, administered before METHOX re-instituted the GH-releasing effect of CLON . METHOX administered at the starting of an arginine infusion (ARG, 10% solution, 3.3 ml/min X 30 min) reduced consistently the GH releasing effect of the latter while, conversely, pretreatment with PRA, strikingly potentiated the GH-releasing effect of the amino acid (2 dogs). METHOX did not alter the GH-releasing effect of human pancreatic GH-releasing factor (hpGRF-40, 1/microgram/kg, iv), though it consistently delayed the occurrence of the GH secretory peak following hpGRF-40. These data indicate that alpha 1-adrenergic receptors located in the central nervous system, inhibit in the dog tonic and stimulated GH secretion.
Assuntos
Hormônio do Crescimento/metabolismo , Receptores Adrenérgicos beta/fisiologia , Animais , Arginina/farmacologia , Clonidina/farmacologia , Cães , Feminino , Cinética , Masculino , Metoxamina/farmacologia , Prazosina/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacosRESUMO
Homologous anterior pituitaries grafted under the kidney capsule in hypophysectomized rats were studied 30 days after transplantation. Some cells maintained the ultrastructural features peculiar to the various cell types of normotopic glands, while the others were characterized by few, small, dense granules, spherical or polymorphic, located peripherally in the cytoplasm. This picture might be due to a functional adaptation which occurs in pituitary cells still producing different hormones, once removed from central nervous system control. The major change in polypeptide hormone composition of graft homogenates relative to normotopic pituitaries is the fall in GH and PRL concentration. The in vitro incorporation of L-[3H]leucine into the two hormones and the release of radioactive GH and PRL from L-[3H]leucine-prelabeled tissue fragments are also greatly decreased. The decrease in concentration, in vitro biosynthesis, and release of GH per mg tissue protein are approximately 87, 91, and 93%, respectively. These results might be due primarily to a decrease in the number of somatotrophs and/or in their secretory activity, with relatively minor changes in GH intracellular transport and turnover. In contrast, a clear-cut fall in in vitro turnover was detected for PRL, as shown by the fact that decreases in biosynthesis and release per mg tissue protein of this hormone (approximately -95% and -99%, respectively) by far exceed the decrease in the tissue concentration (-74%). These data indicate that in in vitro secretory activity of mammotrophs is greatly reduced in the grafts with respect to the normotopic glands. Thus, the high secretory activity previously reported in hypophysectomized rats bearing pituitary grafts should be attributed to the lack of the inhibitory control of the central nervous system rather than to an increase in secretory capacity under nonrestrained conditions.
Assuntos
Hormônio do Crescimento/metabolismo , Hipófise/transplante , Prolactina/metabolismo , Animais , Feminino , Hipofisectomia , Hipófise/citologia , Hipófise/metabolismo , Biossíntese de Proteínas , Ratos , Transplante HomólogoRESUMO
Administration of human pancreatic GH-releasing factor 1-40 (hpGRF-40) at doses of 1, 10, 20, 100, and 500 ng/100 g BW sc induced in 10-day-old rats a clear-cut rise in plasma GH 15-min post-injection, although the effect was not dose-related and peak GH levels were already present after the lowest GRF dose. In 25-day-old rats, hpGRF induced only a slight rise in plasma GH at the dose of 500 ng/100 g BW sc, whereas it was completely ineffective at the lower doses. In 5-day-old rats, hpGRF (20 ng/100 g BW sc twice daily), administered for 5 days, induced a marked rise in pituitary GH content and plasma GH levels determined 14 h after the last hpGRF injection. In these rats, at the end of treatment, a challenge hpGRF dose (20 ng/100 g BW) induced a rise in plasma GH significantly higher than in infant rats receiving only the challenge hpGRF dose. These data show that: 1) pituitary responsiveness to hpGRF is strikingly higher in infant than in post-weaning rats; 2) in infant rats, subacute administration of hpGRF stimulates GH synthesis and release.
Assuntos
Animais Recém-Nascidos/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Animais , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Endogâmicos , Fatores Sexuais , Fatores de Tempo , DesmameRESUMO
LHRH (median eminence) and LH (pituitary and plasma) from male and female Sprague-Dawley rats were assayed 1 month after streptozotocin injection and compared with values in controls either fed ad libitum or offered a restricted diet. Plasma LH was also assayed after stimulation with exogenous LHRH or naloxone. In diabetic males, the median eminence LHRH content and the plasma LH response to exogenous LHRH were unaltered, pituitary LH was increased, and plasma LH was decreased under basal conditions and after naloxone treatment. In diabetic females, while the median eminence LHRH content and the plasma LH response to exogenous LHRH or naloxone were reduced, pituitary and plasma LH levels were not different. Measurements made in undernourished rats excluded the possibility that the alterations found in diabetic animals were nutrition dependent. In parallel experiments, hypothalami and pituitaries were examined morphologically. In diabetic animals, degenerate axons, mainly of the LHRH type, were found in the arcuate nucleus and median eminence, and LH gonadotrophs were altered and more numerous. Strong differences between control males and females were revealed by morphometry; moreover, diabetic females had higher brain weights and fewer LH gonadotroph changes than diabetic males. These studies indicate that 1) the hypothalamo-pituitary changes that occur early in our streptozotocin-treated rats are unrelated to undernourishment and are possibly caused by insulin deficiency; 2) the LHRH axonal lesions might play a primary pathogenic role in the hypothalamo-pituitary disorder; 3) some anatomical data indicate that the brain and pituitary are less severely affected by diabetes in female than in male animals; and 4) differences between control males and females may account for some of the dissimilarities between the sexes observed under diabetic conditions.
Assuntos
Diabetes Mellitus Experimental/patologia , Hipotálamo/patologia , Hipófise/patologia , Animais , Biometria , Peso Corporal , Diabetes Mellitus Experimental/fisiopatologia , Feminino , Privação de Alimentos/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/fisiopatologia , Hormônio Luteinizante/metabolismo , Masculino , Microscopia Eletrônica , Naloxona/farmacologia , Tamanho do Órgão , Hipófise/fisiopatologia , Ratos , Ratos Endogâmicos , Fatores SexuaisRESUMO
We have evaluated the role of gamma-aminobutyric acid (GABA) in the neuroendocrine control of beta-endorphin (beta-EP) secretion in the rat. Plasma beta-EP and beta-lipotropin (beta-LPH) levels and beta-EP-like immunoreactivity (beta-EPLI) in the anterior pituitary (AP) and neurointermediate lobe (NIL) were determined after administration of GABA antagonist or agonist drugs in male rats under resting conditions or after potent physical stresses. Bicuculline (0.1-0.8 mg/kg BW ip), a GABA receptor antagonist, induced a dose-related rise in plasma beta-EP and beta-LPH levels and a concomitant decrease in beta-EPLI concentrations in the AP but not in the NIL. Muscimol, a potent GABA-mimetic drug, did not alter baseline plasma beta-EP and beta-LPH levels, whether given systemically (1.0-2.0 mg/kg BW ip) or intracerebroventricularly (500 ng/kg BW), but prevented the effect of bicuculline on plasma and AP-beta-EP and beta-LPH concentrations. Administration of foot shock or restraint stress induced a clear-cut activation of the AP-related beta-EP secretion, an effect that was prevented by pretreatment with muscimol. Together, these data show that GABA-ergic mechanisms, probably operating at a central nervous system level, exert an inhibitory action on resting and stimulated beta-EP and beta-LPH secretion. Since no alterations in beta-EP concentrations in the NIL occurred after manipulations with GABA-ergic drugs or stress, and these were detected only in the AP, an interaction between GABA-ergic neurons and CRF neurons is the most likely explanation for the reported findings.
Assuntos
Endorfinas/metabolismo , Adeno-Hipófise/metabolismo , Neuro-Hipófise/metabolismo , Ácido gama-Aminobutírico/farmacologia , Animais , Bicuculina/farmacologia , Masculino , Muscimol/farmacologia , Adeno-Hipófise/efeitos dos fármacos , Neuro-Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Estresse Fisiológico/metabolismo , beta-EndorfinaRESUMO
The demonstration that GH-releasing factor (GRF) stimulates GH synthesis and release in rat pups prompted studies to evaluate the effects on the same indices of clonidine (CLO), an alpha 2-adrenoceptor and potent GH secretagogue, purported to act in adult rats via GRF release. Our first aim was to ascertain whether CLO elicits GH release in rat pups via GRF, and if this is the case, to evaluate the ontogenetic development in 1- to 10-day-old pups of the GH response to acute CLO or GRF administration and, finally, the effects of short term CLO or GRF treatment on plasma and pituitary GH concentrations and on the GH response to an acute challenge with the homologous secretagogue. CLO (15 micrograms/100 g BW, sc) induced a clearcut GH rise in 10-day-old rats but not in pups pretreated with a specific anti-GRF serum. Moreover, unlike GRF (10(-8) M), CLO (10(-6) to 10(-5) M) did not stimulate GH release in vitro from anterior pituitaries of 10-day-old rats. In 1-day-old rats, neither CLO (15 micrograms/100 g BW, sc) nor GRF (20 ng/100 g BW, sc) stimulated GH release, whereas significant GH stimulation was elicited by GRF, but not CLO, in 5-day-old rats and by both secretagogues in 10-day-old rats. Short term treatment with CLO (15 micrograms/100 g BW, sc, twice daily) or GRF (20 ng/100 g BW, sc, twice daily) on postnatal days 1 through 5 did not modify either plasma or pituitary GH concentrations 14 h after the last drug administration, but did so when either secretagogue was administered on postnatal days 5 through 9. Finally, an acute challenge with GRF, but not with CLO, induced a further rise in the already elevated plasma GH levels of pups pretreated from postnatal day 5 through 9, but neither secretagogue did so in pups pretreated from postnatal days 1 to 5. Viewed together, these data indicate that in infant rats CLO releases GH via GRF release and that the somatotropes respond earlier to GRF (5 days) than the GRF-secreting structures do to alpha 2-adrenergic stimulation (10 days). Both GRF and CLO stimulate GH synthesis when administered repeatedly. However, whereas repeated GRF treatment has a priming effect on the somatotropes, CLO does not, probably because of down-regulation of hypothalamic alpha 2-adrenoceptors.
Assuntos
Animais Recém-Nascidos/metabolismo , Clonidina/farmacologia , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/biossíntese , Animais , Hormônio do Crescimento/metabolismo , Soros Imunes , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The aim of this study was to evaluate whether in infant rats, as in adult rats, the brain adrenergic mechanisms regulate plasma GH levels and, if so, to determine the contribution of GH-releasing hormone (GHRH) and/or somatostatin (SS) pathways. In 10-day-old rats, activation of alpha 2-adrenoceptors by clonidine (CLO) was effective to stimulate GH release starting from 50 micrograms/kg ip and up to 450 micrograms/kg ip, though no dose-related effect was evident. Conversely, alpha 2-adrenoceptor blockade by yohimbine (YOH, 10 mg/kg, ip) decreased baseline GH levels. Administration of methoxamine (METHOX, 10 micrograms/rat, ip), a alpha 1-adrenoceptor agonist, significantly reduced plasma GH concentrations, while prazosin (5 mg/kg BW, ip), a specific alpha 1-adrenoceptor antagonist, stimulated plasma GH secretion. Administration of an anti-SS serum (SS-ab, 300 microliters, ip) induced a significant rise in plasma GH levels, while administration of an anti-GHRH serum (GHRH-ab, 100 microliters, ip) was associated with a striking fall in GH levels. In rats pretreated with SS-ab, administration of CLO induced a further rise in plasma GH levels. GHRH-ab significantly reduced plasma GH levels, and this effect was not altered by subsequent CLO administration. Administration of SS-ab and YOH resulted in plasma GH levels intermediate between those of rats treated with SS-ab alone or YOH alone, while pretreatment with GHRH-ab induced a lowering of plasma GH greater than when YOH was given alone. in rats pretreated with SS-ab, the GH-lowering effect of METHOX was completely lacking, while GHRH-ab and METHOX induced a lowering of plasma GH similar to that ensuing after METHOX alone or GHRH-ab alone. Administration of prazosin in rats pretreated with SS-ab did not elicit any further rise in plasma GH, while combined administration with GHRH-ab elicited a GH-lowering effect comparable to that elicited by GHRH-ab alone. These data demonstrate that in the infant rat: brain adrenergic mechanisms involved in the neural regulation of GH secretion are operative; different neuropeptide mechanisms mediate the effect of activation or inhibition of alpha 1- and alpha 2-adrenoceptors. In particular, activation of alpha 2-adrenoceptors stimulates GH secretion via endogenous GHRH release, although a mechanism operating to inhibit hypothalamic SS release cannot be excluded; stimulation of alpha 1-adrenoceptors is inhibitory to GH secretion exclusively via an increased release of hypothalamic SS.