The aim of this diploma thesis was association analysis of single nucleotide polymorphism of IGFBP-2 and MC4R genes in a selected group of Czech Large White pigs with indicators of pork quality. The surveyed traits were pH value, color of meat, electrical conductivity, drip loss, contents of intramuscular fat and fatty acids. The polymorphisms were detected by the PCR and RFLP procedures. The allele and genotype frequencies were calculated and results were statistically evaluated using SAS program. In the case of the IGFBP-2 gene was discovered, that the observed set of animals is marked out by the higher percentage of allele B (99,5 %), the relative frequency of the BB genotype was 99 %, AB 1 % and genotype AA has not been found. For this reason, an association analysis could not be performed. The MC4R gene showed a higher frequency of the G allele (74.52%), with the relative frequency of AA genotypes being 2.88%, AG 45.19% and GG 51.92%. On the basis of the association analysis, statistically significant differences were found in the content of the linoleic acid at significance level of P ≤ 0,05 between genotypes AG×GG and to the drip loss where was the difference between the genotypes AA×GG. No statistically significant differences were found for other meat quality indicators, not even value close to significant difference (P ≤ 0,1).

Insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the insulin-like growth factor (IGF-I). However, their precise role is as yet unclear. Further, recent studies have indicated that IGFBP-3 has a receptor mediated growth inhibitory response of its own. In the present study, we quantified the binding characteristics of IGFBP-3 to bovine aortic endothelial (BAE) cells. Binding studies at 4 ^oC were conducted and a specific binding curve for IGFBP-3 was obtained. IGFBP-3 was found to bind with an equilibrium dissociation constant (K_D) value of 3.1 x 10^-10 M. The role of heparan sulfate proteoglycans (HSPG) in the IGFBP-3 binding mechanism was also examined. It was seen that inactivation of the cell surface HSPGs with 75 mM sodium chlorate did not affect IGFBP-3 binding. Further, there have been reports of inhibition of IGFBP-3 binding by heparin in the media. Hence, the most probable interaction of HSPG with IGFBP-3 occurs in the extracellular region, with soluble HSPGs acting as receptors for IGFBP-3 and decreasing the net cell associated ligand receptor interaction. This is likely, since IGFBP-3 is known to possess a heparin binding domain. Simultaneous introduction of IGF-I and IGFBP-3 into the extracellular media decreased IGFBP-3 binding to the cell surface, which might imply that IGF-I and IGFBP-3 regulate each other's action. / Master of Science

No description available.

INTRODUÇÃO Na puberdade, tanto fisiológica quanto precoce, um dos eventos marcantes é o estirão de crescimento. Análogos do GnRH tem sido utilizado como tratamento da puberdade precoce central (PPC) tendo como consequência o bloqueio do eixo gonadal e diminuição da velocidade de crescimento, porém mantém níveis séricos elevados de IGF-I e IGFBP-3. Não existem relatos sobre a expressão do IGF1R durante a puberdade. Considerando-se que este poderia ser um ponto de regulação da velocidade de crescimento, o presente estudo propõe avaliar a expressão do IGF1R em meninas com PPC antes e durante o tratamento. MÉTODOS: Avaliamos meninas com PPC que foram divididas em dois grupos: Grupo A foi constituído por 16 meninas avaliadas antes do início do tratamento com idade média de 8,0+-0,7anos e o Grupo B constituído por 16 pacientes em uso regular do análogo do GnRH com idade média de 9,4+-0,8 anos. O grupo controle foi composto por 18 crianças saudáveis, pré-púberes com idade média 7,1+-1,3 anos. RESULTADOS: A expressão do mRNA do gene do IGF1R foi maior no grupo B quando comparado ao grupo A (p= 0,04) e ao grupo controle (p=0,004). Não foi observado diferença estatística entre o Grupo A e o grupo controle (p=0,17). Os níveis séricos de IGF-I e IGFBP3 assim como a relação molar IGF-I/IGFBP3 foram significativamente maiores no grupo A em relação ao grupo controle. (p<0,0001). Não encontramos diferença nas concentrações de IGF-I, IGFBP3 ou na relação molar entre os grupos A e B. O grupo controle apresentou níveis mais elevados de IGFBP1 quando comparado com os grupos A e B (p<0,001). Ao compararmos somente os grupos A e B, o grupo B apresentou número estatisticamente maior de valores indetectáveis de IGFBP1 quando comparado com o grupo A (p=0,01) mostrando uma tendência a valores menores no grupo B. A dosagem de insulina foi significativamente menor no grupo controle quando comparado ao grupo A (p<0,001) e não apresentou diferença entre os grupos A e B. Ao analisarmos os 3 grupos (controle, A e B) não encontramos a correlação negativa entre insulina e IGFBP-1. Essa correlação aparece quando avaliamos somente o grupo controle e o grupo A (r= - 0,5; p=0,007) e desaparece quando acrescentamos o grupo B na análise. CONCLUSÃO: As variações nas concentrações séricas de IGF-I, IGFBP-3, IGFBP-1 e insulina não explicam a desaceleração da velocidade de crescimento durante o tratamento de meninas com puberdade precoce central com análogos do GnRH. O aumento da expressão do IGF1R parece refletir uma redução da sinalização intracelular do IGF1R com consequente diminuição da bioatividade do IGF-I em um mecanismo de feedback de alça ultra curta. O aumento da secreção do hormônio de crescimento devido a redução do feedback negativo na hipófise, explica as concentrações encontradas de IGF-I, IGFBP3 e IGFBP1.Estudos outros serão necessários para confirmar esta hipótese, avaliando diferentes pontos de sinalização na cascata pós-receptor / BACKGROUND: Growth spurt is a major event in central precocious puberty (CPP). GnRH analogues (GnRHa) treatment inhibit gonadal axis and decrease height velocity. However, serum IGF-I and IGFBP-3 remain high as before treatment. No reports regarding IGF type 1 receptor (IGF1R) in CPP is available. Considering that this could be a point of regulation of height velocity, the present study aims to study IGF1R mRNA expression in girls with CPP before and during GnRHa treatment. MÉTHODS: Sixteen girls with CPP (8.0±0.7yr) were evaluated before treatment (Group A) and sixteen (9.4±0.8yr) in use of GnRHa (Group B). Age-matched pre pubertal children were studied as controls (n=18). Fasting blood sample were collect for IGF1R mRNA expression analysis in peripheral lymphocytes (RT-PCR) and serum IGF-I, IGFBP-3, IGFBP-1 and insulin determination. RESULTS: The expression of IGF1R mRNA was higher in Group B than in Group A (p=0.04) and Controls (p=0.004). No difference was observed between Groups A and Controls. IGF-I, IGFBP-3 and IGF-I/IGFBP3 molar ratio were similar in Group A and B but higher than in Controls (p<0.0001). IGFBP-1 was higher (p<0.0001) in Controls than in Groups A and B. When we compare only Groups A and B, group B showed more IGFBP1 undetectable values than group A (p = 0.01) showing a tendency to lower values in group B. Insulin levels were lower in Controls than in Group A (p<0.001), but no difference were observed between Groups B and A. Negative correlation was found between insulin and IGFBP-1 when controls and Group A were put together (r= -0.5; p=0.007). This correlation disappear if Group B is included in the analysis. CONCLUSION: Serum concentrations of IGF-I, IGFBP-3, IGFBP-1 and insulin do not explain the decrease in height velocity during CPP treatment with GnRH analogue. The increase in IGF1R mRNA expression suggest impairment of IGF-I signaling and compensatory up regulation of the IGF1R. Increased GH concentrations due to reduction of IGF-I feedback could explain the IGF-I, IGFBP-3 and IGFBP-1 findings. Other studies are necessary to confirm this hypothesis by studying different signaling points in post-receptor cascade

INTRODUÇÃO Na puberdade, tanto fisiológica quanto precoce, um dos eventos marcantes é o estirão de crescimento. Análogos do GnRH tem sido utilizado como tratamento da puberdade precoce central (PPC) tendo como consequência o bloqueio do eixo gonadal e diminuição da velocidade de crescimento, porém mantém níveis séricos elevados de IGF-I e IGFBP-3. Não existem relatos sobre a expressão do IGF1R durante a puberdade. Considerando-se que este poderia ser um ponto de regulação da velocidade de crescimento, o presente estudo propõe avaliar a expressão do IGF1R em meninas com PPC antes e durante o tratamento. MÉTODOS: Avaliamos meninas com PPC que foram divididas em dois grupos: Grupo A foi constituído por 16 meninas avaliadas antes do início do tratamento com idade média de 8,0+-0,7anos e o Grupo B constituído por 16 pacientes em uso regular do análogo do GnRH com idade média de 9,4+-0,8 anos. O grupo controle foi composto por 18 crianças saudáveis, pré-púberes com idade média 7,1+-1,3 anos. RESULTADOS: A expressão do mRNA do gene do IGF1R foi maior no grupo B quando comparado ao grupo A (p= 0,04) e ao grupo controle (p=0,004). Não foi observado diferença estatística entre o Grupo A e o grupo controle (p=0,17). Os níveis séricos de IGF-I e IGFBP3 assim como a relação molar IGF-I/IGFBP3 foram significativamente maiores no grupo A em relação ao grupo controle. (p<0,0001). Não encontramos diferença nas concentrações de IGF-I, IGFBP3 ou na relação molar entre os grupos A e B. O grupo controle apresentou níveis mais elevados de IGFBP1 quando comparado com os grupos A e B (p<0,001). Ao compararmos somente os grupos A e B, o grupo B apresentou número estatisticamente maior de valores indetectáveis de IGFBP1 quando comparado com o grupo A (p=0,01) mostrando uma tendência a valores menores no grupo B. A dosagem de insulina foi significativamente menor no grupo controle quando comparado ao grupo A (p<0,001) e não apresentou diferença entre os grupos A e B. Ao analisarmos os 3 grupos (controle, A e B) não encontramos a correlação negativa entre insulina e IGFBP-1. Essa correlação aparece quando avaliamos somente o grupo controle e o grupo A (r= - 0,5; p=0,007) e desaparece quando acrescentamos o grupo B na análise. CONCLUSÃO: As variações nas concentrações séricas de IGF-I, IGFBP-3, IGFBP-1 e insulina não explicam a desaceleração da velocidade de crescimento durante o tratamento de meninas com puberdade precoce central com análogos do GnRH. O aumento da expressão do IGF1R parece refletir uma redução da sinalização intracelular do IGF1R com consequente diminuição da bioatividade do IGF-I em um mecanismo de feedback de alça ultra curta. O aumento da secreção do hormônio de crescimento devido a redução do feedback negativo na hipófise, explica as concentrações encontradas de IGF-I, IGFBP3 e IGFBP1.Estudos outros serão necessários para confirmar esta hipótese, avaliando diferentes pontos de sinalização na cascata pós-receptor / BACKGROUND: Growth spurt is a major event in central precocious puberty (CPP). GnRH analogues (GnRHa) treatment inhibit gonadal axis and decrease height velocity. However, serum IGF-I and IGFBP-3 remain high as before treatment. No reports regarding IGF type 1 receptor (IGF1R) in CPP is available. Considering that this could be a point of regulation of height velocity, the present study aims to study IGF1R mRNA expression in girls with CPP before and during GnRHa treatment. MÉTHODS: Sixteen girls with CPP (8.0±0.7yr) were evaluated before treatment (Group A) and sixteen (9.4±0.8yr) in use of GnRHa (Group B). Age-matched pre pubertal children were studied as controls (n=18). Fasting blood sample were collect for IGF1R mRNA expression analysis in peripheral lymphocytes (RT-PCR) and serum IGF-I, IGFBP-3, IGFBP-1 and insulin determination. RESULTS: The expression of IGF1R mRNA was higher in Group B than in Group A (p=0.04) and Controls (p=0.004). No difference was observed between Groups A and Controls. IGF-I, IGFBP-3 and IGF-I/IGFBP3 molar ratio were similar in Group A and B but higher than in Controls (p<0.0001). IGFBP-1 was higher (p<0.0001) in Controls than in Groups A and B. When we compare only Groups A and B, group B showed more IGFBP1 undetectable values than group A (p = 0.01) showing a tendency to lower values in group B. Insulin levels were lower in Controls than in Group A (p<0.001), but no difference were observed between Groups B and A. Negative correlation was found between insulin and IGFBP-1 when controls and Group A were put together (r= -0.5; p=0.007). This correlation disappear if Group B is included in the analysis. CONCLUSION: Serum concentrations of IGF-I, IGFBP-3, IGFBP-1 and insulin do not explain the decrease in height velocity during CPP treatment with GnRH analogue. The increase in IGF1R mRNA expression suggest impairment of IGF-I signaling and compensatory up regulation of the IGF1R. Increased GH concentrations due to reduction of IGF-I feedback could explain the IGF-I, IGFBP-3 and IGFBP-1 findings. Other studies are necessary to confirm this hypothesis by studying different signaling points in post-receptor cascade

In den letzten Jahren wurde gezeigt, dass die Serumkonzentration des insulinähnlichen Wachstumsfaktorbindungsproteins-2 (IGFBP-2) bei Krebserkrankungen, die mit dem Verlust des Tumorsuppressorgens PTEN einhergehen, erhöht ist und daher möglicherweise einen Marker für den PTEN-Status und die Aktivität des PI3K/AKT/mTOR-Signalweges darstellt. Schmid et al. haben 2014 einen Patienten mit PTEN-Hamartom-Tumor-Syndrom (PHTS) mit einer heterozygoten PTEN-Keimbahndeletion und massiver Lipomatose beschrieben, bei dem erhöhte IGFBP-2 Serumspiegel gemessen wurden. Ziel dieser Arbeit war es zu analysieren, ob PTEN-defiziente Lipomzellen des Patienten im Vergleich zu Kontrollfettzellen mehr IGFBP-2 produzieren, sowie den Einfluss verschiedener pharmakologischer Inhibitoren des AKT/PI3K/mTOR - und des MAPK- Signalwegs auf die IGFBP-2 Produktion zu untersuchen. In der PTEN-defizienten Lipomzellkultur, gewonnen aus reseziertem Lipomgewebe des Patienten, wurden vergleichbare Mengen an IGFBP-2 wie in den nicht PTEN-defizienten Kontrollzellen gefunden. Die pharmakologische Hemmung der PI3K und AKT bewirkten eine signifikante Senkung der IGFBP-2 Expression und Sekretion, wohingegen sich bei Hemmung der MEK und des mTORC1 keine Effekte zeigten. Diese Ergebnisse weisen darauf hin, dass eine heterozygote PTEN-Deletion in Lipomzellen nicht zu einer erhöhten IGFBP-2 Produktion führt und daher die erhöhten Serumspiegel des Patienten nicht darauf zurückzuführen sind. Des Weiteren bestätigen die in vitro Ergebnisse die klinische Beobachtung, dass unter der Therapie mit dem mTORC1-Inhibitor Rapamycin die IGFBP-2 Serumspiegel des Patienten nicht zurückgingen. Möglicherweise stellt IGFBP-2 jedoch einen geeigneten Verlaufsmarker für eine Therapie mit PI3K- oder AKT-Inhibitoren dar.

Master of Science / Department of Animal Sciences and Industry / J. Ernest Minton / Enteric disease and immune challenge are processes that have detrimental effects on growth performance of young swine. The current study tested the hypothesis salmonellae-induced enteric disease would perturb the endocrine growth axis in a serovar dependent fashion. Specifically, we evaluated effects of Salmonella enterica serovar Typhimurium (Typhimurium) and serovar Choleraesuis (Choleraesuis) on critical regulatory components of growth in young swine. Weaned pigs were housed 2 per pen with ad libitum access to feed and water in a 14 d experiment. Pigs were then repeatedly fed either 10[superscript]8 CFU Choleraesuis or 10[superscript]8 Typhimurium in dough balls, with control pigs receiving dough without bacteria. Bacteria were re-fed twice weekly. Rectal temperatures were monitored daily from d 0 to7 and ADFI was measured through d 14. Pigs were weighed and samples of serum were obtained for circulating IGF-I on days 0, 7, and 14. At the conclusion of the study, samples of semitendinosus muscle and liver were obtained and subsequently assayed for IGF-I, IGFBP-3, and IGFBP-5 mRNA. Rectal temperatures were elevated in pigs given Choleraesuis pigs from d 2 through d 7 (P < 0.05) when compared to control pigs and pigs fed Typhimurium. Pigs receiving Choleraesuis had substantially decreased feed intake on days 2, 3, 4, 7, 8, 9, and 10 (P < 0.01), with a trend for reduction on d 5 (P = .08), and they experienced an approximate 25% reduction in BW compared to control and Typhimurium pigs by the conclusion of the study. Pigs given Choleraesuis also experienced marked reductions in circulating IGF-I on d 7 (P < 0.01 vs. control and Typhimurium) with reductions of lesser magnitude on d 14 (P = 0.07 vs. control and P < 0.05 vs. Typhimurium). Treatment tended to affect liver IGFBP-3 mRNA (P = 0.08), where expression tended to be elevated in Typhimurium and Choleraesuis pigs. In contrast, IGFBP-3 mRNA relative abundance was increased (P < 0.03) in pigs given Typhimurium versus control pigs. Muscle IGF-I mRNA was reduced in Choleraesuis pigs compared to control and Typhimurium (P < 0.05). Treatment tended to affect muscle IGFBP-3 mRNA (P = 0.10), where Choleraesuis had numerically less relative abundance than controls. Oral inoculation of growing pigs with Choleraesuis disrupted feed intake and BW gain, and this was accompanied by decreases in circulating IGF-I and reduced muscle expression of mRNA for IGF-I and IGFBP-3.

The ability of exogenous growth hormone (GH) to increase milk yield through insulin-like growth factor-1 (IGF-I) in dairy cows is well characterized. However, recent studies utilizing mammary epithelial cell lines indicate a direct effect of GH on mammary epithelial cells (MEC). To test if these observations are relevant in vivo and if this response differs between dairy breeds, three mammary models were utilized. Mammary explants from a lactating Jersey cow were cultured in classical lactogenic media (dexamethasone, insulin, and prolactin) with 0 or 10 ng/mL of recombinant bovine GH for 12h. Primary MEC from lactating Holstein and Jersey cows were cultured in classical lactation media with 0 or 10 ng/mL of GH for 2, 4, and 7 days. And lastly, MEC isolated from pooled Holstein or pooled Jersey milk were cultured in the same conditions as primary MEC. The response to GH was quantified by the relative abundance of mRNA for two milk protein genes (α-lactalbumin and αS1-casein), the GH receptor, IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) as determined by quantitative RT-PCR. The abundance of α-lactalbumin mRNA in explants was increased in response to GH. After 2 days, Jersey primary MEC showed an increase in GH receptor mRNA, in addition to a noteworthy trend of increasing abundance of IGFBP-3 regardless of GH treatment. After 4 days, Holstein primary cells cultured with GH had decreased IGFBP-3 mRNA. After 7 days, primary cells isolated from Holstein and Jersey mammary tissue showed a slight response to GH. Mammary cells from milk mirrored the responses to GH observed in primary cells: MEC isolated from Holsteins had decreased IGFBP-3 mRNA after 4 days of treatment with GH and MEC isolated from Jerseys showed the same trend of increasing IGFBP-3 abundance between 2 and 4 days, but with no difference between GH treatments. These results indicate that the effect of GH may differ between breeds and indicate GH has a direct effect on mammary epithelial cells, possibly including effects on the abundance of IGFBP-3 mRNA.

Os hormônios de crescimento, principalmente os do eixo GH/IGF-I são responsáveis pelo crescimento tecidual e estrutural desde o nascimento. O GH produzido na hipófise é um hormônio com funções metabólicas e anabólicas e é o principal estimulador da síntese e liberação do IGF-I no fígado que tem suas ações endócrinas, parácrinas e autócrinas mediadas pelas IGFBPs. O exercício físico está intimamente ligado à função anabólica, estimulando a secreção e a ação dos hormônios do eixo GH/IGF-I.Existe a hipótese de haver um comportamento bifásico do eixo durante uma temporada de treinamento,caracterizado por uma fase catabólica, seguida de uma fase anabólica dependendo das fases do treinamento, porém vários estudos têm resultados controversos. O objetivo desse projeto foi investigar o impacto de uma temporada de treinamento em atletas de voleibol sobre o eixo GH/IGF-I e IGFBP-3 e sua relação com desempenho em testes físicos. A amostra foi composta por 10 jogadores de Voleibol categoria adulto da equipe de Franca-SP que foram analisados no início(A1), durante(A2) e ao final(A3) de 15 semanas de treinamento. Foram analisados dados antropométricos, altura de salto e potência de membros inferiores no Squat Jump (SJ), Counter Moviment Jump(CMJ)e Drop Jump 40 cm (DJ40), Índice de Força Reativa (IFR), Razão de Utilização Excêntrica (RUE) e concentrações deIGF-I e IGFBP-3. Para as análises estatísticas foram utilziadas ANOVA de medidas repetidas, Magnitude de Efeito (ES) e Probabilidade Quantitativa de Chances (QC). Os resultados mostram redução dos valores de Massa Coporal Total (MCT), Percentual de Gordura Coporal (%GC), Massa Magra (MM) e Massa Gorda (MG), com menor valor em A3, os resultados dos saltos apresentaram aumento linear com diferença estatísitca (p < 0,05) no DJ40 em A3. A sessão de treino não teve influência sobre as concentrações de IGF-I e IGFBP-3, indicando que a intensidade de disputa dessa modalide não é capaz de alterar as concentrações desses hormônios. Não foi verificada diferença estatísitca (p < 0,05) entre as coletas durante o período de treinamento, mas, as análises de ES e QC indicam tendência de aumento do IGF-I em A3. O comportamento bifásico do eixo GH/IGF-I não foi observado nesse estudo, possivelmente devido a forma de planejamento do período de treinamento, contudo, o IGF-I apresentou maiores concentrações em A3 coincidindo com os maiores resultados de altura de salto. Com esses resultados foi possível inferir que a concentração de IGF-I está correlacionada positivamente com o desempenho físico de atletas de voleibol e que a redução ou a incapacidade de aumento de IGF-I pode ser um sinal de alerta para atletas e treinadores. Ainda assim, são necessários novos estudos para investigar se o treinamento terá efeitos semelhantes durante longos períodos de treinamento, períodos de treinamento com maior intensidade, diferentes fases durante o período de preparação ou competição produzirão respostas hormonais semelhantes / Growth hormones, especially the GH/IGF-I axis is responsible for tissue and structural growth from birth. GH produced in the pituitary gland is a hormone with metabolic and anabolic functions and is the main stimulator for the synthesis and release of IGF-I in the liver that has its endocrine, paracrine and autocrine actions mediated by IGFBPs. Physical exercise is closely linked to anabolic function, stimulating the secretion and action of the hormones of the GH/IGF-I axis. There is a hypothesis of a biphasic behavior of the axis during a training season, characterized by a catabolic phase, followed by an anabolic phase depending on the training phases, but several studies have controversial results. The objective of this project was to investigate the impact of a training season on volleyball athletes on the GH/IGF-I axis and IGFBP-3 and its relation to performance in physical tests. The sample consisted of 10 adult category Volleyball players from the Franca-SP team who were analyzed at baseline (A1), during (A2) and at the end (A3) of 15 weeks of training. Anthropometric data, jump height and power of lower body in Squat Jump (SJ), Counter Movement Jump (CMJ) e Drop Jump 40 cm (DJ40), Reactive Force Index (RFI), Eccentric Usability Ratio (EUR) and IGF-I and IGFBP-3 concentrations were analyzed. Statistical analyzes were performed using repeated measures ANOVA, Effect Size test (ES) and Probability of Quantitative Chances(QC). The results show a reduction in Total Body Mass (TBM) values, Percentage of Body Fat (%BF), Lean Mass (LM) and Fat Mass (FM), with a lower value in A3, the jump results showed a linear increase with a statistical difference (p <0.05) in DJ40 in A3. The training session had no influence on the concentrations of IGF-I and IGFBP-3, indicating that the intensity of contention of this modality is not able to alter the concentrations of these hormones. There was no statistically significant difference (p <0.05) between the collections during the training period, but the ES and QC analyzes indicated an upward trend in IGF-I in A3. The biphasic behavior of the GH/IGF-I axis was not observed in this study, possibly due to the planning of the training period, however, IGF-I presented higher concentrations in A3 coinciding with higher jump height results. With these results it was possible to infer that the concentration of IGF-I is positively correlated with the physical performance of volleyball athletes and that the reduction or inability to increase IGF-I may be a warning signal for athletes and coaches. Still, further studies are needed to investigate whether training will have similar effects during long periods of training, more intense training periods, different phases during the preparation or competition period will produce similar hormonal responses.

O eixo GH/IGF-I (hormônio do crescimento - fatores de crescimento insulina-símile) é um sistema de mediadores de crescimento, receptores e proteínas de ligação que controlam o crescimento somático e tecidual em muitas espécies e programas de exercícios estão relacionados a esta função anabólica por meio da ação deste eixo. Partindo deste pressuposto, o objetivo do presente estudo foi analisar a cinética das concentrações séricas de IGF-I, IGFBP-3 e ALS, das citocinas IL-6, IL-10 e TNF-? e comparar com o desempenho físico e a composição corporal de nadadores adolescentes nas diferentes fases de uma temporada de treinamento. A amostra foi composta por 9 nadadores adolescentes do sexo masculino com idade entre 16 e 19 anos, que faziam parte de uma equipe de natação universitária da cidade de Ribeirão Preto. Os níveis de IGF-I, IGFBP-3, ALS, IL-6, IL-10 e TNF-? foram determinados na fase básica, específica e final do polimento. A fim de comparar a cinética do sistema IGF-I/IGFBP-3-ALS e das citocinas com o desempenho físico e a composição corporal dos atletas, também foram avaliadas a resistência aeróbia em nado livre, a aptidão anaeróbia em nado atado, a massa corporal, o percentual de gordura e a massa magra nos diferentes momentos da temporada. Para a análise da cinética do sistema IGF-I/IGFBP-3-ALS e das citocinas nas diferentes fases do treinamento e antes e após a sessão de treino padronizada foram utilizados os testes não-paramétricos de Friedman e Wilcoxon, respectivamente, adotando-se um nível de significância de 0,05. A correlação entre duas variáveis foi analisada por meio do coeficiente de correlação de Spearman. Resultados: o IGF-I é sensível aos efeitos agudos e crônicos do treinamento, apresentando um comportamento em duas fases ao longo da temporada - uma fase catabólica (fase específica) e uma fase anabólica (polimento). O IGFBP-3 mostrou-se sensível apenas aos efeitos crônicos do treinamento, não sendo possível identificar um comportamento diferenciado intra-fase (pré x pós). A ALS manteve-se constante, mostrando que não foi afetada pelos efeitos agudos ou crônicos do treinamento. A IL-10 mostrou-se sensível aos efeitos agudos e crônicos do treinamento, aumentando significativamente durante a fase de polimento. A IL-6 não apresentou variação significante em resposta a uma sessão de treinamento (efeito agudo), apesar disso, apresentou uma correlação negativa com o IGF-I na fase específica de treinamento. O TNF-? apresentou concentrações mais estáveis ao longo da temporada. A composição corporal e a condição cardiorrespiratória dos nadadores não foram alteradas ao longo da temporada. O Pico de Força e a Força Média acompanharam a variação do IGF-I e do IGFBP-3, ou seja, diminuíram durante a fase específica e apresentaram uma elevação significativa durante o polimento. Conclusão: o IGF-I e a IGFBP-3 podem ser considerados um dos sensíveis marcadores de estado de treinamento, podendo orientar treinadores e atletas a dosar a intensidade de treinamento, especialmente de jovens que se encontram na puberdade. Foi possível observar algumas faces de interação com as citocinas, onde a soma das ações das citocinas provavelmente explicariam as mudanças nas concentrações séricas de IGF-I e IGFBP-3. / The GH/IGF-I axis is a system of growth mediators, receptors, and binding proteins that regulate somatic and tissue growth; and it has been shown that exercise programs are related to the anabolic function of this axis. The aim of this study was to analyse the kinetics of serum IGF-I, IGFBP-3, ALS, IL-6, IL-10 and TNF-? concentration in adolescent swimmers at different stages of a training season, and compare them with physical performance parameters and body composition of the athletes. Nine male athletes, aged 16 to 19 years and who trained regularly throughout the season were included in this study. Serum IGF-I, IGFBP-3, ALS, IL- 6, IL-10, and TNF-? concentrations were recorded before and after (pre x post) standardized training sessions during the different stages of a training season (extensive x intensive x tapering). Aerobic endurance in freestyle, anaerobic fitness in tied swimming (Peak Force and Average Force), body mass, fat percentage, and lean body mass were also analysed at the different stages of training in order to compare the behaviour of the IGF-I/IGFBP/ALS system with the physical performance and body composition of the athletes. Variations in the cytokines and IGF-I/IGFBP-3/ALS system before and after a standardized training session, and at the different stages of training were analysed by the Wilcoxon and Friedman nonparametric tests, respectively. The correlation between the two variables was analysed by the Spearman\'s correlation coefficient. Significance was considered at P<0.05. Results: IGF-I was sensitive to the acute and chronic effects of training, exhibiting biphasic behaviour throughout the season. The catabolic phase was characterized by a reduction in serum IGF-I levels during the intensive stage while the anabolic phase was marked by an increase in posttraining serum IGF-I levels during the tapering stage. IGFBP-3 was only sensitive to the chronic effects of training, with a reduction in post-training serum levels during the intensive stage and an increase during the tapering stage. No difference was observed in pre- or posttraining IGFBP-3 levels at the different stages. ALS and TNF-? remained estable throughout the training season. IL-10 was sensitive to the acute and chronic effects of training, increasing significantly during the tapering phase. IL-6 showed no variation in response to a training session (acute effect); nevertheless, it had a negative correlation to IGF-I at the intensive phase. The body composition and cardiorespiratory function of the swimmers remained unaltered throughout the season. Peak Force and Average Force followed IGF-I and IGFBP-3 variations, with a decrease during the intensive stage and a significant increase during the tapering stage. The body composition and cardiorespiratory condition of the swimmers did not vary significantly throughout the season, exhibiting behaviour independent of IGF-I or IGFBP-3. Conclusion: Serum IGF-I and IGFPB-3 concentrations have proven to be sensitive markers of training status and, thus, may be used as guides for coaches and athletes in the challenging task of modulating training intensity in young athletes. The cytokine interactions observed suggest that the combined effects of these cytokines may be responsible for the serum IGF-I and IGFBP-3 variations recorded.