RESUMO
Following health agencies warning, the use of animal origin supplements should be avoided in biological products proposed as therapy in humans. Platelet lysate and several other growth factors sources are alternatives to replace fetal calf serum, the current gold standard in clinical-grade cell culture. However, the platelet supplement's content lacks data due to different production methods. The principle behind these products relays on the lysis of platelets that release several proteins, some of which are contained in heterogeneous granules and coordinate biological functions. This study aims to analyze the composition and reproducibility of a platelet lysate produced with a standardized method, by describing several batches' protein and particle content using proteomics and dynamic light scattering. Proteomics data revealed a diversified protein content, with some related to essential cellular processes such as proliferation, morphogenesis, differentiation, biosynthesis, adhesion, and metabolism. It also detected proteins responsible for activation and binding of transforming growth factor beta, hepatocyte growth factor, and insulin-like growth factor. Total protein, biochemical, and growth factors quantitative data showed consistent and reproducible values across batches. Novel data on two major particle populations is presented, with high dispersion level at 231 ± 96 d.nm and at 30 ± 8 d.nm, possibly being an important way of protein trafficking through the cellular microenvironment. This experimental and descriptive analysis aims to support the content definition and quality criteria of a cell supplement for clinical applications.
Assuntos
Produtos Biológicos , Células-Tronco Mesenquimais , Somatomedinas , Animais , Plaquetas/metabolismo , Diferenciação Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Meios de Cultura/química , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Proteômica , Reprodutibilidade dos Testes , Soroalbumina Bovina/análise , Soroalbumina Bovina/metabolismo , Somatomedinas/análise , Somatomedinas/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
The study postulated that differential nutritional management during the early lactation period would be reflected in endometrial expression of genes related to embryo growth at the end of the voluntary waiting period. Thus, the effect of the combined use of total mixed ration (TMR) and grazing under different herbage allowances during the first 75 days post-partum (DPP) on endometrial gene expression was evaluated in primiparous dairy cows. Cows were blocked by body weight, age and body condition score and randomly assigned to three grazing treatments: high (HA, 30 kg DM per cow per day), medium (MA, 15 kg DM per cow per day) and low (LA, 7.5 kg DM per cow per day) herbage allowance (mixed pasture, 2,600 kg DM per ha) plus 8 kg DM of supplement or TMR (55% forage, 45% concentrate) fed ad libitum (TMR) from calving to 75 DPP. At 57 DPP, cows were synchronized for oestrus (day 0, 68 DPP) and at day 7, endometrial biopsies were obtained. The nutritional treatment did not affect insulin, IGF-1 and leptin concentrations on days 0, 4 or 7. Expression of IGF1, IGFBP3, IGFBP4, ADIPOR1 and ADIPOR2 mRNA was significantly affected by the nutritional treatment. Endometrial IGF1 and IGFBP4 mRNA were twofold greater in TMR and HA than MA and LA cows. Expression of IGFBP3 and ADIPOR1 mRNAs was greater in TMR and HA than MA cows, but did not differ from LA cows. All groups had greater expression of ADIPOR2 mRNA than MA cows. This study provided solid evidence of the importance of nutritional management during early lactation on uterine environment at the end of the voluntary waiting period. The greater expression of genes related to embryo growth and uterine function (IGF system, progesterone and adiponectin receptors) in cows fed diets maximizing energy intake suggests a favourable environment for embryonic growth, which may explain the improved reproductive performance of cows in good energy balance.
Assuntos
Bovinos/fisiologia , Dieta/veterinária , Endométrio/metabolismo , Regulação da Expressão Gênica , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Feminino , Insulina/sangue , Lactação/fisiologia , Leptina/sangue , RNA Mensageiro , Receptores de Adiponectina/sangue , Somatomedinas/análiseRESUMO
The objective of this study was to evaluate the effects of a single intramammary infusion of Panax ginseng extract (GS) on insulin-like growth factors (IGF) in bovine mammary gland during early involution. Eight mammary quarters from six nonpregnant cows in late lactation were infused with 10 mL of ginseng extract solution (3 mg/mL), six quarters were treated with 10 mL of placebo (vehicle alone) and six quarters were maintained as uninoculated controls. Milking was interrupted after infusion. Concentrations of IGF1 in mammary secretions were higher in GS-treated quarters than in placebo and uninoculated control quarters at 24, 48 and 72 h post-treatment (p<0.05). Treatment with GS did not affect mammary secretion of IGF2 (p=0.942). At 7 d of post-lactational involution, a decrease of immunostained area and mRNA expression for IGF1 was observed in mammary tissue of GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). The IGF2 immunostained area and mRNA expression for this growth factor were not affected by GS treatment (p=0.216 and p=0.785, respectively). An increase in protein levels and mRNA expression in mammary tissue of IGFBP3, IGFBP4 and IGFBP5 was observed in GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). These results provide evidence that intramammary inoculation of GS extract at cessation of milking may promote early mammary involution through the inhibition of IGF1 local production and bioavailability.
Assuntos
Glândulas Mamárias Animais/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Somatomedinas/efeitos dos fármacos , Animais , Bovinos , Feminino , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like II/biossíntese , Fator de Crescimento Insulin-Like II/efeitos dos fármacos , Lactação/efeitos dos fármacos , Glândulas Mamárias Animais/química , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Somatomedinas/análise , Somatomedinas/biossínteseRESUMO
OBJECTIVES: The aim of this study was to evaluate the reactivity of steroid hormone receptors (SHRs), dystroglycans (DGs), matrix metalloproteinases (MMPs), insulin-like growth factor receptor (IGFR-1), and laminin (Lam) in both prostatic stromal and epithelial compartments showing different diseases in elderly men. METHODS: Sixty prostatic samples were obtained from 60- to 90-year-old patients (mean 63 years) with and without prostatic lesions from Hospital of the School of Medicine, State University of Campinas (UNICAMP). The Samples were divided into standard (no lesions); high grade prostatic intraepithelial neoplasia (HGPIN); prostatic cancer (PC); and benign prostatic hyperplasia (BPH) groups. The samples were submitted to immunohistochemistry and Western blotting analyses. Research Ethics Committee of the School of Medicine, University of Campinas/UNICAMP (number 0094.0.146.000-08). RESULTS: The results showed increased IGFR-1 and MMPs protein levels in the PC and HGPIN groups. Decreased αDG and ßDG protein levels were verified in the PC and HGPIN groups. Androgen receptor (AR) reactivity was similar among all groups. Estrogen receptor α (Erα) immunoreactivity was more intense in the epithelium in the PC and HGPIN groups. Estrogen receptor ß (ERß) immunoreactivity was weak in the epithelium of the HGPIN and PC groups. CONCLUSIONS: To conclude, there was an association among IGFR-1, MMPs, and SHRs, indicating IGFR-1 as a target molecule in prostate therapy, considering the IGF proliferative properties. Also, the distinct SHRs reactivities in the lesions in both prostatic compartments indicated different paracrine signals and pointed out the importance of estrogenic pathways in the activation of these disorders.
Assuntos
Distroglicanas/análise , Metaloproteinases da Matriz/análise , Doenças Prostáticas/patologia , Receptores de Esteroides/análise , Somatomedinas/análise , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Western Blotting , Humanos , Imuno-Histoquímica , Laminina/análise , Masculino , Pessoa de Meia-Idade , Próstata/patologiaRESUMO
AIMS: To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. METHODS: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (≥ 48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. RESULTS: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. CONCLUSION: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Desenvolvimento Infantil/efeitos dos fármacos , Transtornos do Crescimento/sangue , Transtornos do Crescimento/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Somatomedinas/análise , Biomarcadores/sangue , Índice de Massa Corporal , Pré-Escolar , Feminino , Transtornos do Espectro Alcoólico Fetal/sangue , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Leptina/sangue , Masculino , Gravidez , Estudos ProspectivosRESUMO
A Síndrome de Noonan (SN) é caracterizada por baixa estatura proporcionada de início pós-natal, dismorfismos faciais, cardiopatia congênita e deformidade torácica. A frequência da SN é estimada entre 1:1000 e 1:2500 nascidos vivos, com distribuição semelhante em ambos os sexos. A herança é autossômica dominante com penetrância completa, porém a maioria dos casos é esporádica. Até o momento, mutações em genes da via RAS-MAPK (PTPN11, KRAS, SOS1, RAF1, MEK1, NRAS e SHOC2) foram identificadas em aproximadamente 70% dos pacientes. Uma das principais características fenotípicas da SN é a baixa estatura pós-natal, embora o mecanismo fisiopatológico do déficit de crescimento nesta síndrome ainda não esteja totalmente esclarecido. Estudos que avaliaram o padrão de crescimento linear em crianças com SN foram realizados anteriormente ao conhecimento do diagnóstico molecular dessa síndrome. No presente estudo, avaliamos a frequência de mutação nos genes PTPN11, SOS1, RAF1 e KRAS em 152 pacientes com SN e o padrão de crescimento linear (altura) e ponderal [índice de massa corpórea (IMC)] dos pacientes com mutação identificada. No total, mutações nos genes relacionados foram encontradas em 99 pacientes (65%) do nosso estudo, com predominância do gene PTPN11 (47%), seguido do SOS1 (9%), RAF1 (7%) e KRAS (3%). Foram construídas curvas específicas para SN de Altura e IMC para idade e sexo utilizando o método LMS. Os pacientes com SN apresentaram crescimento pré-natal preservado, porém o comprometimento do crescimento pós-natal foi observado desde o primeiro ano de vida, atingindo uma altura final de -2,5 e -2,2 desvios-padrão da média para população brasileira em homens e mulheres, respectivamente. O prejuízo da altura foi maior nos pacientes com mutação no gene RAF1 em comparação com os genes PTPN11 e SOS1. O IMC dos pacientes com SN apresentou queda de 1 desvio-padrão em relação à média da população brasileira normal. O comprometimento do IMC foi menor...
Noonan Syndrome (NS) is characterized by distinctive facial features, short stature and congenital heart defects. The estimated prevalence is 1:1000 to 1:2500 live births, affecting equally both sexes. It is an autosomal dominant disorder with complete penetrance, but most cases are sporadic. To date, mutations in the RAS/MAPK pathway genes (PTPN11, KRAS, SOS1, RAF1, MEK1, NRAS and SHOC2) were identified in approximately 70% of patients. One of the cardinal signs of NS is proportional postnatal short stature although the physiopathological mechanism of growth impairment remains unclear. The current knowledge about the natural history of growth associated with NS was described before molecular diagnosis era. In this study, we performed PTPN11, SOS1, RAF1, and KRAS mutation analysis in a cohort of 152 NS patients and studied the natural linear (height) and ponderal growth [body mass index (BMI)] of NS patients with related mutations. Mutations in NS-causative genes were found in 99 patients (65%) of our cohort. The most common mutated gene was PTPN11 (47%), followed by SOS1 (9%), RAF1 (7%) and KRAS (3%). Sex-specific percentile curves for height and BMI were constructed using the LMS method. NS patients had birth weight and length within normal ranges but the postnatal growth impairment was observed during the first year of life, reaching a final height of -2.3 and -2.2 standard deviations from the mean for Brazilian healthy men and women, respectively. Postnatal growth impairment was higher in RAF1 mutation patients than in patients with SOS1 and PTPN11 mutations. BMI values in NS patients were lower in comparison with normal Brazilian population. BMI values were higher in patients with RAF1 mutations than in patients with other genotypes. Patients with mutations in PTPN11 and SOS1 genes were more likely to have pulmonary valve stenosis, whereas hypertrophic cardiomyopathy was more common in patients with mutations in the gene RAF1...
Assuntos
Humanos , Masculino , Feminino , Crescimento/genética , Fator de Crescimento Insulin-Like I/análise , Hormônio do Crescimento/análise , MAP Quinase Quinase Quinases/genética , Proteínas Son Of Sevenless/genética , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/etiologia , Síndrome de Noonan/genética , Somatomedinas/análise , Transtornos do Crescimento/genéticaRESUMO
Simple childhood obesity is characterized by normal or even accelerated growth in spite of reduced growth hormone (GH) secretion. There are conflicting reports on the effects of obesity upon components of the GH-insulin-like growth factor-I (IGF-I)-IGF binding proteins (IGFBPs) system. In the present study we aimed to determine GH, IGF-I, IGFBP-3 and IGFBP-2 as well as some of the less explored components of this axis (IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments, and total acid labile subunit [ALS]) in 22 obese and 17 age-matched control children. We also evaluated not only total GH binding protein (GHBP) serum levels but also GHBP bound to GH (complexed) in both groups. Obese and control groups strongly differed in BMI (obese: 4.7 +/- 0.36 vs control: 0.37 +/- 0.25 SDS, p <0.0001). In the obese group, we found lower GH serum levels, but normal serum levels of GH-GHBP complex, IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Obese children presented higher total circulating GHBP (6.0 +/- 0.44 vs 2.9 +/- 0.29 nmol/l, p <0.001) and insulin levels (10.5 +/- 1.5 vs 5.1 +/- 0.8 mU/l, p <0.001), while IGFBP-2 (4.6 +/- 0.5 vs 6.6 +/- 0.7%, p <0.05) and the ratio IGFBP-2/IGF-I (0.032 +/- 0.019 vs 0.095 +/- 0.01, p = 0.013) were lower than in controls. BMI and insulin were directly, and IGFBP-2 serum levels inversely, correlated to total GHBP serum levels when multiple regression analysis was performed (r = 0.74, p <0.001). By stepwise regression analysis, insulin (r = -0.37, p <0.05) and BMI (r = -0.52, p <0.01) inversely determined IGFBP-2. In summary, obese children present normal growth in spite of reduced GH secretion, probably because the combination of increased total GHBP and normal GH-GHBP complex serum levels (suggesting increased GH receptor [GHR] number and a normal serum GH reservoir, respectively) allow for the achievement of normal levels of IGF-I, IGFBP-3, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Reduced IGFBP-2 serum levels and a lower ratio of IGFBP-2/IGF-I in obese children may suggest an increase of tissue IGF-I bioavailability, thus promoting its action. Normal IGF-I and GH availability may be contributing to maintain normal growth in obese children.
Assuntos
Índice de Massa Corporal , Proteínas de Transporte/sangue , Hormônio do Crescimento Humano/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Obesidade/sangue , Somatomedinas/análise , Composição Corporal , Estatura , Criança , Humanos , Insulina/sangue , Análise por Pareamento , Obesidade/fisiopatologia , Puberdade/metabolismo , Valores de ReferênciaRESUMO
The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.
Assuntos
Corpo Lúteo/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Fase Luteal/fisiologia , Óxido Nítrico/metabolismo , Somatomedinas/metabolismo , Adulto , Arginina/farmacologia , Corpo Lúteo/química , Corpo Lúteo/efeitos dos fármacos , Técnicas de Cultura , Estradiol/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like II/metabolismo , Doadores de Óxido Nítrico/farmacologia , Progesterona/metabolismo , Receptor IGF Tipo 1/análise , Somatomedinas/análiseRESUMO
The partnership the insulin-like growth factor (IGF) in women with polycystic ovary syndrome (PCOS) is characterized by mechanisms underlying alterations in the GH/IGF-1, axis. In the pathogenesis exist a synergism markedly enhanced between IGF-1 and insulin, and IGF-1 with LH to increase androgen production, causing a reduced IGFBPs and SHBG production, the resulting hyperandrogenism, within and outside the ovary, may inhibitor follicular maturation and the biosynthesis of estrogen. At the present, the data suggests up to date paracrine, autocrine as well as endocrine actions in the ovary in normal conditions and the lost of this homeostasis can be followed by neuro-endocrine.
Assuntos
Síndrome do Ovário Policístico/metabolismo , Somatomedinas/metabolismo , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Somatomedinas/análiseRESUMO
In this review main hormones involved in development and muscle growth are shown with special emphasis on growth hormone (GH) and insulin-like growth factors (IGF). Chemist composition, synthesis place, action way and main action mechanisms of these hormones are reviewed. Nutritional factors which modified seric metabolites, and their effects on hormone secretion are detailed. It was observed that GH, IGF, thyroid hormones, insulin, glucocorticoids and sexual steroids act in a complex and cordinated way to produce a productive response to different> nutritional strategies.
Assuntos
Animais Domésticos/crescimento & desenvolvimento , Hormônio do Crescimento Humano/fisiologia , Somatomedinas/fisiologia , Animais , Glucocorticoides/fisiologia , Hormônio do Crescimento Humano/sangue , Insulina/fisiologia , Desenvolvimento Muscular , Estado Nutricional , Somatomedinas/análise , Hormônios Tireóideos/fisiologiaRESUMO
En esta revisión se describen las principales hormonas invlolucradas en el desarrollo y crecimiento muscular, haciendo especial énfasis en la hormona de cricimiento (GH) y los factores del crecimiento semejante a insulina (IGF). Se recopila la composición química, el lugar de síntesis y los principales mecanismos de acción de estas hormonas. Se observó que la GH, IGF, las hormonas tiroideas, la insulina, los glucocorticoides y los esteroides sexuales actuán en una forma compleja y coordinada para producir una respuesta productiva a diferentes estrategias nutricionales.
Assuntos
Animais , Animais Domésticos/crescimento & desenvolvimento , Hormônio do Crescimento Humano/fisiologia , Estado Nutricional , Somatomedinas/fisiologia , Glucocorticoides/fisiologia , Hormônio do Crescimento Humano/sangue , Insulina/fisiologia , Músculos/crescimento & desenvolvimento , Somatomedinas/análise , Hormônios Tireóideos/fisiologiaRESUMO
En esta revisión se describen las principales hormonas invlolucradas en el desarrollo y crecimiento muscular, haciendo especial énfasis en la hormona de cricimiento (GH) y los factores del crecimiento semejante a insulina (IGF). Se recopila la composición química, el lugar de síntesis y los principales mecanismos de acción de estas hormonas. Se observó que la GH, IGF, las hormonas tiroideas, la insulina, los glucocorticoides y los esteroides sexuales actuán en una forma compleja y coordinada para producir una respuesta productiva a diferentes estrategias nutricionales. (AU)
Assuntos
Animais , Estado Nutricional , Hormônio do Crescimento Humano/fisiologia , Somatomedinas/fisiologia , Animais Domésticos/crescimento & desenvolvimento , Hormônio do Crescimento Humano/sangue , Somatomedinas/análise , Músculos/crescimento & desenvolvimento , Hormônios Tireóideos/fisiologia , Insulina/fisiologia , Glucocorticoides/fisiologiaRESUMO
Children with chronic renal failure (CRF) often have retarded growth, and abnormalities of the growth hormone-insulin-like growth factor (GH-IGF) axis in CRF may contribute to this growth failure. The serum GH and IGF levels are normal in these children, but IGF bioactivity is low as a result of excess IGF binding proteins (IGFBPs) in the 35 kd serum fractions. The levels of intact IGFBP-1, -2, and -6 and of a 29 kd IGFBP-3 fragment are all high, and the IGFBP-1 and -2 levels correlate negatively with height. Children with CRF who are treated with GH show catch-up growth that correlates positively with the increase in each component of the 150 kd serum ternary complex (acid-labile subunit, IGFBP-3, IGF-I, and IGF-II). Consistent with this observation, the increase in IGFBP-3 levels is confined to the 150 kd serum fractions. Serum levels of IGFBP-1, -2, and -6 do not rise, but serum IGF bioactivity does. Thus GH appears to induce an increase in the ternary complex in the serum of children with CRF. It is possible that IGFs released by the 150 kd serum complex promote growth by overcoming the inhibitory effects of excess IGFBPs in the 35 kd serum fractions.
Assuntos
Hormônio do Crescimento Humano/fisiologia , Falência Renal Crônica/fisiopatologia , Somatomedinas/fisiologia , Estatura/efeitos dos fármacos , Estatura/fisiologia , Criança , Crescimento/efeitos dos fármacos , Transtornos do Crescimento/tratamento farmacológico , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/fisiologia , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Falência Renal Crônica/complicações , Peso Molecular , Somatomedinas/análiseRESUMO
BACKGROUND: Euglycemic or hyperglycemic clamp and the frequently sampled i.v. glucose tolerance test are the most frequently used methods to assess insulin resistance. However, both are expensive and cumbersome. AIM: To evaluate the relative or discriminatory usefulness of sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and insulin like growth factor binding protein 1 (IGFBP-1) as markers of insulin resistance and to estimate the tissue sensitivity to insulin by means of the insulin tolerance test (ITT) and the frequently sampled i.v. glucose tolerance test (IVGTT) in normal, obese and hyperandrogenic women. SUBJECTS AND METHODS: Six normal, 6 obese and 12 hyperandrogenic women of similar ages, were studied. In two consecutive days, the ITT and the IVGTT were performed and a basal blood sample was obtained to measure SHBG, DHEAS and IGFBP-1. Insulin sensitivity was calculated as the blood glucose slope in the ITT and with the minimal model of Bergman in the IVGTT. RESULTS: Insulin sensitivity, measured with ITT was 0.58 (0.53-0.63) in normal, 0.38 (0.05-0.59) in obese and 0.20 (0.0-0.36) in hyperandrogenic women. The figures for the IVGTT were 7.97 (4.1-15.4), 2.41 (0.81-4.89) and 1.1 (0.46-1.88), respectively. Both methods had a positive correlation coefficient of 0.792 (p < 0.001). SHBG was 87.0 m 37.9 and 18.3 nmol/l in normal, obese and hyperandrogenic women, respectively (p < 0.09). IGFBP-1 values were 3.0, 2.1 and 1.6 ng/ml respectively (p < 0.05). DHEAS values were 132, 190 and 206 ug/dl, respectively (ND). CONCLUSIONS: ITT is a simple and reliable method to assess insulin sensitivity. SHBG discriminates subjects with different levels of insulin sensitivity. Since it is easy to measure, it could be used as a marker on insulin sensitivity.
Assuntos
Hiperandrogenismo/diagnóstico , Resistência à Insulina , Obesidade/diagnóstico , Adulto , Biomarcadores/sangue , Glicemia/análise , Desidroepiandrosterona/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperandrogenismo/sangue , Insulina/sangue , Obesidade/sangue , Globulina de Ligação a Hormônio Sexual/análise , Somatomedinas/análiseRESUMO
Insulin-like growth factors (IGFs) are growth hormone-dependent anabolic peptides that circulate in biologic fluids complexed to a family of IGF binding proteins. Measurement of the serum concentrations of IGF peptides and IGF binding proteins has proved to be an effective means of evaluating functional growth hormone status and makes it possible to establish a diagnosis of IGF deficiency.
Assuntos
Transtornos do Crescimento/diagnóstico , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Somatomedinas/análise , Western Blotting , Ensaio de Imunoadsorção Enzimática , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/deficiência , Hormônio Liberador de Hormônio do Crescimento/uso terapêutico , Humanos , Radioimunoensaio , Somatomedinas/fisiologiaRESUMO
Women in whom anorexia nervosa develops during adolescence have failure of linear growth associated with low levels of insulin-like growth factor I (IGF-1). To investigate the pathophysiology of growth retardation in adolescents with anorexia nervosa, we measured basal growth hormone (GH), growth hormone-binding protein (GHBP), IGF-1, and insulin-like growth factor binding protein-3 (IGFBP-3) in three groups of patients: (1) 28 recently hospitalized female adolescents with anorexia nervosa, (2) 23 of the same patients after partial weight restoration, and (3) 28 healthy control subjects matched for age, sex, and pubertal stage. Fasting GH levels in group 1 did not differ significantly from those in group 3. In contrast, serum GHBP (p < 0.001), IGF-1 (p < 0.001), and IGFBP-3 (p < 0.01) were significantly lower in group 1 than in group 3. Serum GHBP and IGFBP-3 levels were positively correlated with body mass index. Serum GHBP levels were low in patients in all five pubertal stages and even in those shown to have adequate GH secretion. In group 2 (after refeeding) the serum IGF-1 concentration increased significantly and GHBP and IGFBP-3 returned to normal. We conclude that patients with anorexia nervosa have diminished GH action resulting in decreased secretion of IGF-1. The positive correlation with body mass index and the reversibility with refeeding suggest that these changes are secondary to malnutrition. Altered GH function that occurs during the years of active growth can explain the growth retardation seen in anorexia nervosa.
Assuntos
Anorexia Nervosa/fisiopatologia , Hormônio do Crescimento/metabolismo , Somatomedinas/análise , Adolescente , Adulto , Anorexia Nervosa/tratamento farmacológico , Anorexia Nervosa/metabolismo , Metabolismo Basal , Índice de Massa Corporal , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Criança , Feminino , Hormônio do Crescimento/sangue , Inibidores do Crescimento/sangue , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/análiseAssuntos
Fator de Crescimento Insulin-Like I/análise , Somatomedinas/análise , Adolescente , Adulto , Envelhecimento/sangue , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Radioimunoensaio/métodos , Padrões de Referência , Valores de Referência , Análise de RegressãoRESUMO
Because patients with uremia have evidence for growth hormone resistance, we investigated whether this resistance can be overcome by administration of recombinant human growth hormone in supraphysiologic doses in children with severe uremia. Nine stunted children with end-stage renal disease (median age 5.8 years, median bone age 2.7 years) were treated with recombinant human growth hormone, 4 IU/m2/day subcutaneously, for a period of 1 year. Median height velocity was increased from 4.4 cm/yr before therapy to 8.0 cm/yr during treatment. Negative values for height velocity standard deviation scores for chronologic age were improved from a median of -2.6 to +1.5 without advancing bone age more than chronologic age. The growth hormone-insulin-like growth factor I resistance may be explained in part by the increased serum concentration of the high molecular weight insulin-like growth factor binding protein despite normal insulin-like growth factor I serum concentration. Treatment with recombinant human growth hormone improved the ratio between the serum concentrations of insulin-like growth factor I and its binding protein, and normalized the somatomedin bioactivity in the growth cartilage bioassay.
Assuntos
Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Falência Renal Crônica/complicações , Determinação da Idade pelo Esqueleto , Estatura , Superfície Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/administração & dosagem , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Falência Renal Crônica/sangue , Masculino , Proteínas Recombinantes , Dobras Cutâneas , Somatomedinas/análise , Uremia/sangue , Uremia/complicaçõesRESUMO
Somatomedin-C concentrations were measured by a newly available commercial radioimmunoassay in plasma samples from 41 children undergoing clinical evaluation of hypothalamic-pituitary function because of varied disorders of growth. Sequential Sm-C levels were stable; the coefficient of variation remained below 10% over a three-hour period. The Sm-C values of 27% of the children were discordant with the GH responses; of 25 patients with normal provoked-GH levels, seven had low Sm-C values, whereas four of 16 patients with inadequate GH responses had normal Sm-C concentrations. All of the discordant data occurred in 31 patients with diminished linear growth velocity. More patients with decreased growth velocity had diminished Sm-C levels than did short children with normal linear growth velocity. These data suggest that many variables, in addition to adequacy of GH production and plasma Sm-C levels, may affect net Sm-C activity. This possibly reduces the usefulness of the Sm-C radioimmunoassay as a single screening test for abnormalities of GH secretion.