Molecular heterogeneity of human GH: From basic research to clinical implications

Boguszewski, César Luiz

doi:10.1007/bf03345170

Cited by 23 publications

(19 citation statements)

References 142 publications

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“…In addition, the stomach derived peptide ghrelin represents an additional stimulus for GH secretion, acting through the GH secretagogue (GHS) receptors expressed in somatotroph cells. After secretion, roughly 40-45% of circulating GH binds to a high-affinity GH binding protein (GHBP), which represents the extracellular domain of the GH receptor (GHR) [9]. GHRs are ubiquitously distributed and they are present as constitutive dimers in the cell membranes.…”

Section: Gh and Igf Systemmentioning

confidence: 99%

“…Growth hormone stimulates the production of IGF-I primarily by the liver, which is the major source of circulating IGF-I, IGFBPs, and, plausibly, IGF-II [9,11]. IGF-I is also produced in several other tissues in response to GH and exerts a negative feedback effect on GH secretion by stimulation of somatostatin release in the hypothalamus and inhibition of GH gene transcription in the pituitary.…”

Section: Gh and Igf Systemmentioning

confidence: 99%

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Growth hormone, insulin-like growth factor system and carcinogenesis

Boguszewski

Kopchick

2015

Endokrynologia Polska

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The growth hormone (GH) and insulin-like growth factor (IGF) system plays an important role in the regulation of cell proliferation, differentiation, apoptosis, and angiogenesis. In terms of cell cycle regulation, the GH-IGF system induces signalling pathways for cell growth that compete with other signalling systems that result in cell death; thus the final effect of these opposed forces is critical for normal and abnormal cell growth. The association of the GH-IGF system with carcinogenesis has long been hypothesised, mainly based on in vitro studies and the use of a variety of animal models of human cancer, and also on epidemiological and clinical evidence in humans. While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, with several of its components being currently tested as central targets for cancer therapy, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker. In this review, we will attempt to consolidate this data. StreszczenieOś hormon wzrostu (GH)-insulinopodobny czynnik wzrostu (IGF) odgrywa istotną rolę w regulacji proliferacji i różnicowania komórek, apoptozy i angiogenezy. Oś GH-IGF wpływa na regulację cyklu komórkowego przez pobudzenie szlaku wzrostu komórki w stosunku do szlaków sygnałowych prowadzących do śmierci komórki, a ostateczny efekt oddziaływania tych dwóch sił ma podstawowe znaczenie dla prawidłowego lub nieprawidłowego wzrostu komórki. Hipotezy na temat powiązań osi GH-IGF z karcynogenezą pojawiły się wiele lat temu, głównie w oparciu o wyniki badań in vitro oraz badań z wykorzystaniem różnych zwierzęcych modeli raka występującego u ludzi. Chociaż liczne dane doświadczalne potwierdzają rolę osi GH-IGF sprzyjającą rozwojowi i progresji nowotworów, a nad kilkoma składowymi tej osi trwają obecnie badania oceniające ich przydatność jako główne cele terapii przeciwnowotworowej, to jednak siła dowodów uzyskanych u chorych z akromegalią, niedoborem GH lub osób leczonych GH jest znacznie słabsza. W niniejszej pracy przeglądowej spróbowano zebrać wszystkie te dane.

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Section: Gh and Igf Systemmentioning

confidence: 99%

Section: Gh and Igf Systemmentioning

confidence: 99%

Growth hormone, insulin-like growth factor system and carcinogenesis

Boguszewski

Kopchick

2015

Endokrynologia Polska

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“…Tentou-se criar ensaios mais sensíveis e específicos, e que apresentassem boa acurácia. Desenvolveram-se, então, ensaios chamados não competitivos, como, por exemplo, os ensaios imunoenzimáticos, imunoquimioluminescentes e imunofluorométricos (19). Esses ensaios diferem um pouco do RIE tradicional porque o reagente "marcado" não é o antígeno, mas o anticorpo.…”

Section: Ensaiosunclassified

“…A calibração de ensaios ultra-sensíveis, que utilizam anticorpos monoclonais, com calibradores biossintéticos representa outra possibilidade de erro, porque o GH da amostra e o GH do calibrador não reagem identicamente com o anticorpo (19).…”

Section: Calibradoresunclassified

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

Casagrande

Czepielewski

2007

Arq Bras Endocrinol Metab

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RESUMOA dosagem do GH no soro é essencial para confirmar ou excluir o seu excesso. Na acromegalia, a ausência de critérios clínicos suficientemente sensíveis para monitorizar o sucesso do tratamento faz com que o GH sérico seja o procedimento de escolha e, para isso, é essencial que a sua dosagem seja realizada de forma confiável, capaz de permitir interpretações uniformes. Vários critérios hormonais têm sido propostos para caracterizar remissão da acromegalia, incluindo níveis séricos de GH randômico inferior a 2,5 µg/l, nadir de GH durante o teste de tolerância oral a glicose inferior a 1,0 µg/l e IGF-I normal para sexo e idade. A importância do tratamento adequado consiste na possibilidade de reverter a mortalidade prematura da acromegalia através da diminuição dos níveis de GH para valores menores que 2,5 µg/l. Com o surgimento de ensaios ultra-sensíveis para medida do GH, tornaram-se necessários critérios mais estritos para determinar cura ou remissão da doença. Nesta revisão, descreveremos aqui as modificações decorrentes da evolução dos ensaios, as conseqüências nos resultados de GH e os pontos de corte propostos na literatura para caracterização da atividade e remissão da acromegalia. ABSTRACT Growth Hormone (GH) and IGF-I Assays: Methodological Aspects and its Implications in Acromegaly Diagnosis and Follow-Up.Growth hormone quantification in serum is essential for confirming or ruling out its excess. The absence of clinical criteria sufficiently sensitive to evaluate the treatment success enables GH as the key diagnostic procedure and for that, its measurements must be done in a reliable way and must allow uniform interpretation. Several different biochemical criteria for remission have been suggested in the past, including a random GH measurement less than 2.5 µg/l, mean GH value from a day curve less than 2.5 µg/l, nadir GH value after an oral glucose tolerance test (OGGT) less than 1.0 µg/l and a normal age-related IGF-I level. The importance of adequate treatment is highlighted by data indicating that lowering GH levels to less than 2.5 µg/l reverses the premature mortality of acromegaly. With the advances of ultrasensitive assays for GH measurement, strictest remission criteria to determine remission or cure were necessary. In this review, we describe the changes of assay methodology and its consequences in serum GH results and cut off point values to define activity and remission of acromegaly.

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“…A forma 22kDa (191 aminoácidos) é a mais comum, sendo decorrente da transcrição do gene GH-N. Um mecanismo de splicing alternativo do gene GH-N dá origem à forma 20kDa e alterações pós-translacionais às formas 5kDa e 17kDa. Há também formas acidificadas, glicosiladas e oligoméricas (34). Os ensaios imunométricos se baseiam na utilização de dois anticorpos monoclonais de alta especificidade.…”

Section: -Ensaios De Gh Utilizados No Brasilunclassified

Diagnóstico e tratamento da acromegalia no Brasil

Donangelo

Une

Gadelha

2003

Arq Bras Endocrinol Metab

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RESUMOAcromegalia é uma doença debilitante e desfigurante que, se não controlada adequadamente, reduz a expectativa de vida do paciente.Complicações cardiovasculares e respiratórias representam as principais causas de morte nos acromegálicos. Atualmente, o diagnóstico é realizado de acordo com as diretrizes do consenso de 2000: ausência de supressão do GH para um valor <1ng/mL e IGF-1 elevado. Avanços em todas as modalidades terapêuticas têm ocorrido, propiciando o controle bioquímico da doença em um número cada vez maior de pacientes. Estudos prévios mostraram que a obtenção de níveis seguros de GH (GH médio <2,5ng/mL) e de IGF-1 normal reduz a taxa de mortalidade para o normal. Em 2002, foram publicadas diretrizes para o manejo da acromegalia, o qual envolve, muitas vezes, uma abordagem multidisciplinar. Neste artigo, fazemos uma avaliação crítica do que dispomos no Brasil para seguirmos as diretrizes estabelecidas nos consensos sobre diagnóstico e tratamento da acromegalia. ABSTRACT Diagnosis and Treatment of Acromegaly in Brazil.Acromegaly is a disabling and disfiguring illness, which, if not adequately controlled, decreases life expectancy. Cardiovascular and respiratory complications represent the main causes of death in acromegalic patients. Nowadays, the diagnosis is made following the guidelines reported in the 2000 consensus: Failure of GH to suppress to less than 1ng/mL and an increased IGF-1. Progress in all therapeutic modalities has been made, allowing biochemical disease control in more patients. Previous studies demonstrated that achieving safe GH levels (mean GH <2.5ng/mL) and normal IGF-1 decreases mortality rate to normal. In 2002, the guidelines for management of acromegaly were published which encompass, many times, a multidisciplinary approach. In this article, we critically evaluate what is available in Brazil that allows us to follow the guidelines established in the diagnosis and treatment consensus.

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Molecular heterogeneity of human GH: From basic research to clinical implications

Cited by 23 publications

References 142 publications

Growth hormone, insulin-like growth factor system and carcinogenesis

Growth hormone, insulin-like growth factor system and carcinogenesis

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

Diagnóstico e tratamento da acromegalia no Brasil

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