Insulin signaling in the whole spectrum of GH deficiency

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

Growth hormone in the tumor microenvironment

ABSTRACT Tumor development is a multistep process whereby local mechanisms enable somatic mutations during preneoplastic stages. Once a tumor develops, it becomes a complex organ composed of multiple cell types. Interactions between malignant and non-transformed cells and tissues create a tumor microenvironment (TME) comprising epithelial cancer cells, cancer stem cells, non-tumorous cells, stromal cells, immune-inflammatory cells, blood and lymphatic vascular network, and extracellular matrix. We review reports and present a hypothesis that postulates the involvement of growth hormone (GH) in field cancerization. We discuss GH contribution to TME, promoting epithelial-to-mesenchymal transition, accumulation of unrepaired DNA damage, tumor vascularity, and resistance to therapy. Arch Endocrinol Metab. 2019;63(6):568-75

O Sistema do Hormônio de Crescimento: interações com a pele / Growth Hormone System: skin interactions

O artigo descreve o Sistema do Hormônio de Crescimento (GH), enfatizando suas possíveis ações nas células da epiderme, nas estruturas da derme e na cicatrização de feridas cutâneas. Para tanto, fez-se uma revisão dos conhecimentos sobre o hormônio do crescimento, seu receptor, a proteína carreadora deste hormônio e demais proteínas envolvidas no mecanismo que o GH utiliza para a sua manifestação nos tecidos cutâneos.

This paper describes the growth hormone system, emphasizing its possible effects on epidermal cells, dermal structures and wound healing. A review of the literature was conducted on studies concerning the growth hormone molecule, its receptor and carrier proteins and the other proteins involved in the mechanisms of its manifestation in dermal tissue.

Prostate cancer and acromegaly: [review] / Câncer de próstata e acromegalia: [revisão]

Acromegalic patients have an increased prevalence of prostatic disorders compared to age-matched healthy subjects. Increased size of the whole prostate or the transitional zone, together with an elevated incidence of other structural changes, such as nodules, cysts, and calcifications, have been reported. Prostate enlargement in young acromegalic patients with low testosterone levels due to central hypogonadism supports the hypothesis that chronic GH and IGF-I excess cause prostate hyperplasia. The relationship between prostatic carcinoma and acromegaly is, until now, only circumstantial. Long-term follow-up of these patients is necessary since epidemiologic studies showed association between serum IGF-I levels in the upper normal limit and prostate cancer in the general population. This review approaches prostate diseases in patients with acromegaly.

Pacientes com acromegalia têm uma prevalência aumentada de desordens prostáticas em comparação a controles saudáveis da mesma idade. Aumento do tamanho de toda a próstata ou da zona de transição, juntamente com uma incidência elevada de outras alterações estruturais, como nódulos, cistos e calcificações, foi descrito. O aumento da próstata em acromegálicos jovens e com níveis baixos de testosterona devido ao hipogonadismo central sugere que o excesso crônico do GH e do IGF-I cause hiperplasia prostática. A relação entre câncer de próstata e acromegalia é, até o momento, apenas circunstancial. Entretanto, um seguimento prolongado desses pacientes é necessário uma vez que estudos epidemiológicos reportaram uma associação entre níveis séricos de IGF-I no limite superior da normalidade e câncer de próstata na população geral. Esta revisão aborda as patologias prostáticas em pacientes com acromegalia.

Fisiologia do eixo GH-sistema IGF / Physiology of the GH-IGF axis

O crescimento, principal característica da infância e da adolescência, apresenta padrão semelhante na maioria dos indivíduos. A herança genética e os componentes do eixo GH-IGF são os fatores que diretamente influenciam esse processo. O GH, produzido na hipófise, exerce sua ação sobre o crescimento mediante regulação do sistema IGF. Os IGFs (IGF-1 e IGF-2) são fatores de crescimento produzidos na maioria dos órgãos e tecidos do organismo, possuindo ações autócrinas, parácrinas e endócrinas sobre o metabolismo intermediário, proliferação, crescimento e diferenciação celular. Associam-se com elevado grau de especificidade e de afinidade à família de seis proteínas carreadoras, denominadas IGFBPs (IGFBP-1 a -6), as quais modulam suas bioati-vidades. A maioria das ações conhecidas dos IGFs é exercida mediante sua ligação com o receptor tipo 1 (IGF-1R). Neste artigo será revisada a composição e a regulação do eixo GH-sistema IGF, assim como a participação de cada um dos seus diferentes componentes no processo de regulação do crescimento humano.

Growth, the main characteristic of childhood and adolescence, has a similar pattern in the majority of the individuals. Genetic background and GH-IGF axis are the factors that directly influence this process. Pituitary GH acts on growth mainly through the regulation of IGF system. The IGFs (IGF-1 and IGF-2) are growth factors produced in the majority of the organs and body tissues. They have autocrine, paracrine and endocrine actions on metabolism and cell proliferation, growth and differentiation. The IGFs bind with high specificity and affinity to a family of 6 binding proteins, called IGFBPs (1 to 6) that modulate their bioactivity. Most of the known IGF actions are mediated via IGF type 1 receptor (IGF1R). In this article we are going to review the composition and regulation of the GH-IGF axis and the role of each component in the regulation of the growth process.

Crecimiento y estado nutricional de niños venezolanos con síndrome de down / Growth and nutritional status in venezuelan children with down`s syndrome

Evaluar el crecimiento, estado nutricional y enfermedades asociadas en niños con Síndrome de Down que asistieron a la consulta de Nutrición, Crecimiento y Desarrollo del "Hospital de Niños J.M de Los Ríos" durante los años 2003 al 2005. Estudio descriptivo, transversal y retrospectivo en pacientes con Síndrome de Down. Se registro: edad, género, peso, talla, perímetro cefálico, circunferencia media del brazo izquierdo y pliegues cutáneos tricipital y subescapular. Se revisaron enfermedades asociadas y número de hospitalizaciones. Para el diagnóstico nutricional y de crecimiento se utilizaron como referencias el Estudio Transversal de Caracas (ETC), el Nacional Center Health Statistics (NCHS) y las Gráficas de Cronk, con sus respectivos puntos de corte. Se incluyeron 41 pacientes, 26 de género femenino y 15 de género masculino, con edades entre 15 días y 15 años de edad, se evidenció talla baja en el 83 por ciento y desnutrición en 88 por ciento al utilizar como referencias el NCHS. Con gráficas específicas para Síndrome de Down se determinó talla baja en 32 por ciento y desnutrición en 85 por ciento. 69 por ciento de los niños con talla baja tenían cardiopatías congénitas y 15 por ciento hipotiroidismo. La talla en los niños con Síndrome de Down evaluados se relacionó significativamente con desnutrición. El uso de guías de supervición de salud y gráficas de crecimiento específicas para Síndrome de Down, son herramientas útiles para vigilar la nutrición, el crecimiento y brindar atención integral a estos niños.

To evaluate growth, nutritional condition and associate diseases in children with Down’s syndrome who attend an out patient clinic of Nutrition, Growth and Development of the “Hospital de Niños J.M de Los Ríos” during 2003 to 2005. A descriptive, cross-sectional and retrospective study was performed. It was registered: Age, heigth, weight, cephalic perimeter, left arm average circumference, tricipital and subescapular skin fold. Associate diseases and number of hospitalizations were reviewed. For growth and nutritional diagnosis were used as references the Cross-sectional Study Caracas (ETC), Nacional Center Health Statistics (NCHS) and the Graphs of Cronk, with respective cut points. 41 patients were included, 26 females and 15 males, with ages between the 15 days and 15 years old. There was short stature in 83% of the children and malnutrition in 88% when comparing them with NCHS charts. With Down’s syndrome specific growth charts, there was short stature in 32% of the children and this one was associated to malnutrition in 85%, congenital heart defect in 69% and hypothyroidism in 15%. Short statures in children with Down syndrome evaluated were related significantly to malnutrition. Health supervision guides and Down syndrome specific growth charts are useful tools to watch the nutrition, growth and to offer integral attention to these children.

Novel mechanisms of growth hormone regulation: growth hormone-releasing peptides and ghrelin

Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.

Rol fisiológico del eje somatotrófico GH-IGF y otras hormonas en el crecimiento de los animales domésticos. Influencia del estado nutricional / Physiologic role of the somatotrophic GH-IGF and others hormones in the domestic animals growth. Influence of the nutritional status

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.

Primary growth hormone insensitivity syndrome - A case reporte

Aproximadamente 230 casos da síndrome de insensibilidade ao GH (síndrome de Laron) foram descritos até o presente, e destes, dois o foram no Brasil. Esta síndrome caracteriza-se por achados clínicos de deficiência severa de hormônio do crescimento, associados à níveis séricos elevados de GH. Estamos relatando o terceiro paciente brasileiro, o primeiro do mundo com descendência portuguesa, que se apresentou com quadro clínico e laboratorial típicos da doença.