RESUMEN

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

Asunto(s)

RESUMEN

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

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

We studied the features of parallel immunoneuroendocrine responses in patients with different degrees of chronic Chagas myocarditis (indeterminate, mild/moderate or severe). A systemic inflammatory scenario was evident in patients with severe myocarditis compared to healthy subjects. This was paralleled by a disrupted activation of the hypothalamus-pituitary-adrenal axis, characterized by decreased concentrations of dehydroepiandrosterone-sulfate (DHEA-s) and an unbalanced cortisol/DHEA-s ratio, reinforcing the view that severe Chagas disease is devoid of an adequate anti-inflammatory milieu, likely involved in pathology. Our study constitutes the first demonstration of neuroendocrine disturbances, in parallel to a systemic inflammatory profile, during progressive human Chagas disease.

Asunto(s)

RESUMEN

Sleep deprivation (SD) produces numerous deleterious changes in brain cells, including apoptosis. It has been demonstrated that growth hormone (GH) stimulates cell growth and counteracts apoptosis, although this anti-apoptotic effect has not been tested against SD. To determine the protective effect of GH administration on cell proliferation and survival in the dentate gyrus (DG) of the hippocampus after sleep deprivation; we injected Wistar adult rats with a low dose of recombinant human GH (rhGH 5 ng/kg) per seven days and then we gently sleep deprived the animals for 48 consecutive hours. 5-Bromodeoxiuridine (BrdU) was administered to assess cell proliferation after the GH treatment and NeuN was used as marker of cell fate. Our results indicate that GH produced a three fold increase in the number of BrdU positive cells within the DG [Control = 1044 ± 106.38 cells, rhGH = 2952 ± 99.84 cells, P<0.01]. In contrast, 48 h of SD significantly reduced cell proliferation but this effect was antagonized by the GH administration [SD = 540 ± 18.3 cells, rhGH + SD = 1116 ± 84.48 cells, P<0.004]. Paradoxically, SD and GH administration increased cell survival separately but no significantly compared with control animals. However, cell survival was increased in animals treated with rhGH+SD compared to rats injected with saline solution [P<0.04]. Within the survival cells, the percentage of neurons was higher in SD animals [95%] compared with saline group, while this percentage (NeuN positive cells) was increased in animals treated with rhGH+SD [120%] compared with rhGH [25%] alone. Our findings indicate that GH strongly promotes cell proliferation in the adult brain and also protects the hippocampal neuronal precursors against the deleterious effect of prolonged sleep loss.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

In the context of the cross-talk between the neuroendocrine and immune systems, it is well known that growth hormone (GH) exerts physiological effects in central as well as peripheral compartments of the immune system. GH modulates a variety of thymic functions, including proliferation of thymocytes and thymic epithelial cells (TEC). Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the organ. GH also stimulates the secretion of cytokines and chemokines by the thymic microenvironment, as well as the production of extracellular matrix proteins. These effects lead to an increase in thymocyte migratory responses and intrathymic traffic of developing T cells, including the export of thymocytes from the organ, as ascertained by experimental studies with intrathymic injection of GH in normal mice and with GH-transgenic animals. Most likely, GH effects in the thymus are mediated by an IGF-1/IGF-1 receptor circuitry, which physiologically operates in nonstimulated conditions in both thymocytes and TECs. Since GH enhances thymus replenishment and increases intrathymic T-cell traffic, ultimately modulating thymocyte exit, it should be placed as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy, and examples recently appeared in the literature are promising and strongly indicate that GH can be beneficial for individuals suffering severe immunodeficiency.

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Noonan syndrome (NS) is one of the most common syndromes transmitted by a mendelian mode. In recent years, germline mutations that affect components of the RAS-MAPK (mitogen-activated protein kinase) pathway were shown to be involved in the pathogenesis of NS and four rare syndromes with clinical features overlapping with NS: Leopard syndrome, cardio-facio-cutaneous syndrome, Costello syndrome and neurofibromatosis type 1. Several hormones act through receptors that stimulate the RAS-MAPK pathway, and therefore, NS and related disorders represent a remarkable opportunity to study the implication of the RAS-MAPK pathway in different endocrine systems. Additionally, children with NS frequently are referred to the endocrinologist because of short stature, delayed puberty and/or undescended testes in males. In this paper, we review the diagnostic, clinical and molecular aspects of NS and NS-related disorders.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

Adrenarche is the direct consequence of the organogenesis of the zona reticularis (ZR). Proliferation of cortical cells could take place in the outermost layers of the adrenal cortex. Cells could then migrate to differentiate the zona glomerulosa (ZG) and zona fasciculata (ZF) during fetal life, and the ZR during postnatal life. After adrenarche, there are detectable increases in circulating DHEA and DHEA-S. Adrenarche could result from an increase in 17,20-lyase activity of P450c17 secondary to high levels of cytochrome b(5) expression, and from a decrease in 3betaHSD2 expression along with an increase in the expression of SULT2A1 in the ZR. The GH-IGF system and insulin, among other factors, might also modulate adrenal androgen production. Furthermore, high concentrations of estradiol enhance basal and ACTH-stimulated DHEA-S production, while aromatase expression was observed in the human adrenal medulla but not in the ZR, suggesting that estrogens produced in the adrenal medulla might be involved in the regulation of androgen production in the ZR. Premature adrenarche might be associated with ovarian hyperandrogenism and polycystic ovarian syndrome in females, as well as with insulin resistance in both sexes. However, many questions remain, transforming adrenal androgens into markers of diseases important for human health.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)