Plurihormonal PIT1-lineage pituitary neuroendocrine tumors: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups (P=0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency / 中国当代儿科杂志

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.

Adenoma hipofisario ectópico del seno esfenoidal persistente tras cirugía manejado con tratamiento conservador / Ectopic pituitary adenoma in the sphenoid sinus persistent after surgery managed with conservative treatment

Los adenomas hipofisarios ectópicos (EPA) constituyen un reto diagnóstico, dada su escasa prevalencia y variada presentación en la que puede incluirse un síndrome de hipersecreción de hormonas hipofisarias. La clínica suele ser larvada e inespecífica, no presentan ninguna característica radiológica diferencial y el diagnóstico habitualmente es anatomopatológico. Sin embargo, a pesar de ser tumores benignos, pueden presentar un comportamiento agresivo, con invasión ósea y difícil resección completa, por lo que un diagnóstico de sospecha precoz podría resultar en un tratamiento más eficaz y con un menor número de complicaciones. Presentamos el caso de una paciente con un adenoma hipofisario ectópico silente en el seno esfenoidal con inmunohistoquímica positiva para Hormona de crecimiento (GH) y prolactina que presentaba restos tumorales tras la intervención quirúrgica y ha sido manejada con tratamiento médico conservado, con buenos resultados.

Ectopic pituitary adenomas constitute a diagnostic challenge, given their low prevalence and varied presentation in which a pituitary hormone hypersecretion syndrome may be included. Clinical symptoms are usually latent and nonspecific, they have no differential radiological characteristics and the diagnosis is usually anatomopathological. However, despite being benign tumors, they can exhibit aggressive behavior, with bone invasion and difficult complete resection, so a diagnosis of early suspicion could result in more effective treatment and fewer complications. We present the case of a patient with a silent ectopic pituitary adenoma in the sphenoid sinus with positive immunohistochemistry for Growth Hormone (GH) and prolactin who had tumor remnants after surgery and was managed with conservative medical treatment, with good results.

Uso da somatotropina recombinante bovina em búfalas leiteiras II: metabolismos energético e mineral / Use of recombinant bovine somatotropin (rbST) in dairy buffaloes II: energy and mineral metabolism

Avaliou-se a influência da somatotropina recombinante bovina (rbST) sobre os metabolismos energético e mineral de búfalas entre 63e 154 dias em lactação. Foram utilizadas 22 búfalas, distribuídas em dois grupos experimentais: grupo rbST - aplicação de 500mg de rbST a cada 14 dias; grupo Controle - sem aplicação de rbST. A cada sete dias, foram coletadas amostras de sangue para a determinação do perfil bioquímico e mensuraram-se a produção de leite e o escore de condição corporal dos animais. As médias dos parâmetros estudados para os grupos rbST e Controle foram, respectivamente: produção de leite (PL): 6,44kg vs. 6,68kg; escore de condição corporal-ECC (1-5): 3,51 vs. 3,57; glicose: 70,58 vs. 64,81mg/dL (P = 0,0003); colesterol: 132,38 vs. 133,40mg/dL; triglicérides: 29,18 vs. 28,32mg/dL; proteína total: 8,57 vs. 8,75g/dL; albumina: 3,47 vs. 3,60g/dL; ureia: 32,46 vs. 33,86mg/dL; creatinina: 1,27 vs. 1,39mg/dL; cálcio:10,25 vs. 10,73mg/dL; fósforo:5,76 vs. 5,62mg/dL; e magnésio:3,70 vs. 3,70mg/dL. O uso de 500mg de rbSTinfluenciou o metabolismo da glicose, porém não modificou a PL, o ECC e os níveis dos demais parâmetros metabólicos estudados.(AU)

The aim was to evaluate the influence of recombinant bovine somatotropin (rbST) on the energy and mineral metabolism of buffaloes between 63 - 154 days in milk. Twenty-two buffaloes distributed in two experimental groups were used: Group rbST (n= 11) - application of 500mg of rbST every 14 days; Control Group (n= 11) - no rbST. Every seven days, blood samples were taken to determine the biochemical profile, and milk production and body condition score were measured. The averages of the variables for rbST and Control groups were, respectively: milk yield (MY) - 6.44kg vs. 6.68kg; body condition score (BCS) - 3.51 vs 3.57 (1-5); glucose - 70.58 vs. 64.81mg/dL (P = 0.0003); cholesterol - 132.38 vs. 133.40mg/dL; triglycerides -29.18 vs. 28.32mg/dL; total protein - 8.57 vs. 8.75g/dL; albumin - 3.47 vs 3.60g/dL; urea - 32.46 vs 33.86mg/dL; creatinine - 1.27 vs 1.39mg/dL; calcium - 10.25 vs. 10.73mg/dL; phosphorus - 5.76 vs 5.62mg/dL; and magnesium - 3.70 vs 3.70mg/dL. Use of 500mg rbST influenced glucose metabolism, but did not modify the MY, BCS and the levels of the other metabolic parameters studied.(AU)

Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Endoscopic transnasal approach for removing pituitary tumors / Acesso transnasal endoscópico para remoção de tumores da hipófise

To describe a series of 129 consecutive patients submitted to the resection of pituitary tumors using the endoscopic transsphenoidal approach in a public medical center. Method: Retrospective analysis based on the records of patients submitted to the resection of a pituitary tumor through the endoscopic transsphenoidal approach between 2004 and 2009. Results: One hundred and twenty-nine records were analyzed. The tumor was non-secreting in 96 (74.42%) and secreting in 33 patients (22.58%). Out of the secretory tumors, the most prevalent was the growth hormone producer (7.65%), followed by the prolactinoma, (6.98%). Eleven patients developed cerebral spinal fluid (CSF) fistulas, and four of them developed meningitis. One patient died due to intracerebral hemorrhage in the postoperative period. Conclusion: The endoscopic transsphenoidal approach to sellar tumors proved to be safe when the majority of the tumors were non-secreting. The most frequent complication was CSF. This technique can be done even in a public hospital with financial limits, since the health professionals are integrated. .

Descrever uma série de 129 pacientes submetidos à ressecção de tumor de hipófise com acesso endoscópico transesfenoidal em um serviço de público referência em Belo Horizonte. Método: Análise retrospectiva realizada por análise dos prontuários de pacientes submetidos à ressecção de tumor de hipófise com acesso endoscópico transesfenoidal entre os anos 2004 e 2009. Resultados: Foram avaliados 129 prontuários. O tumor era não secretante em 96 (74,42%) e secretante em 33 pacientes (22,58%). Dos tumores secretores, o de maior prevalência foi o produtor de hormônio do crescimento: 15 pacientes (7,65%). Onze pacientes desenvolveram fístula liquórica. Um paciente faleceu devido hemorragia intracerebral no pós-operatório. Conclusão: O acesso endoscópico transfenoidal aos tumores selares mostrou-se seguro numa população em que a maioria dos tumores era não secretante. A principal complicação encontrada foi fístula liquórica. Esta técnica é passível de utilização em hospital público mesmo com limites financeiros desde que haja integração multiprofissional. .

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

Treatment of Periapical Lesion with Platelet Rich Fibrin.

Periapical surgery aims to remove periapical pathology to achieve complete wound healing and regeneration of bone and periodontal tissue. Platelet rich fibrin (PRF) is a wonderful tissue engineering product and has gained much popularity due its promising results in wound healing bone induction. The features of this product are an attribute of platelet cells, which, after cellular interactions, release growth factors. This case report illustrates the use of PRF in bony regeneration after enucleation of cyst in anterior maxilla.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.

El tejido graso como modulador endocrino: Cambios hormonales asociados a la obesidad / Adipose tissue as an endocrine modulator: Hormonal changes associated with obesity

Adipose tissue not only stores fat, but secretes factors and hormones, which modify the regulation, metabolism and secretion of several other hormones. The objective of this review is to describe the hormonal disorders associated with increased adipose tissue, which acts as a modulator or disruptor of the endocrine physiology, with special reference to cortisol, androgens, growth hormone and thyroid axis, and discuss the implications for the management and treatment of these patients.

Hypophosphataemic rickets/osteomalacia: A descriptive analysis.

Background & objectives: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. Methods: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. Results: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 – 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1- 3 μg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. Interpretation & Conclusions: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25 – hydroxy vitamin D.

Estudo clínico e molecular em uma coorte de portadores de deficiência de hormônio de crescimento na Bahia / Clinical and molecular study in a cohort of patients with growth hormone deficiency in Bahia

A deficiência de hormônio do crescimento (DGH) tem incidência estimada entre 1/4.000 a 1/10.000 nascidos vivos e pode ser isolada ou associar-se a outras deficiências hormonais. Como não há exame “padrão-ouro”, o seu diagnóstico baseia-se em critérios antropométricos associados a pico diminuído de GH após testes de estímulos farmacológicos. Mais recentemente, a presença de ectopia do lobo posterior hipofisário (ELP) à ressonância nuclear magnética de hipófise (RNMH) tem sido considerada marcador de DGH e mutações em genes associados à embriogênese hipofisária têm sido descritas nesse pacientes. O objetivo do trabalho foi descrever as características clínicas, moleculares e radiológicas de uma coorte de portadores de DGH, acompanhada num mesmo centro de referência (Centro de Diabetes e Endocrinologia da Bahia), entre dezembro de 1998 e dezembro de 2009. Métodos: todos os pacientes realizaram avaliação da função hipofisária e RNMH. O estudo foi dividido em duas partes. Na primeira, foram incluídos apenas pacientes com DGH e ELP (n=130), sendo realizada a caracterização fenotípica da população. Além disso, mutações nos genes HESX1, LHX4 e OTX2 foram avaliadas em 104 pacientes, pelos métodos de PCR e SSCP ou PCR e sequenciamento. Na segunda parte do estudo, foi comparada a resposta terapêutica no primeiro ano de tratamento com hormônio do crescimento nos pacientes com (n=58) e sem (n=26) ELP. Resultados: No subgrupo de pacientes com ELP observou-se grande variabilidade fenotípica. Deficiência hormonal hipofisária combinada foi descrita em 61,5% dos pacientes, sendo mais frequente naqueles nos quais a haste hipofisária não foi visualizada. Malformações cerebrais ocorreram em 9,2% dos pacientes. Trinta pacientes apresentaram mutações, não descritas anteriormente, em genes associados à embriogênese hipofisária, sendo 26 no LHX4 e cinco no HESX1. Mutações no OTX2 não foram identificadas nessa população. A segunda parte do estudo evidenciou que a velocidade de crescimento durante o tratamento com GH foi similar nos pacientes com e sem ELP. Conclusões: o estudo, que avaliou a maior casuística de pacientes com DGH associada à ELP já descrita, confirma a heterogeneidade fenotípica da população, além da baixa prevalência de mutações na mesma. Além disso, ao contrário de estudos prévios, demonstra que a presença de ELP não se associou a melhor resposta ao tratamento com GH.

Perfil metabólico de touros da raça Nelore (Bos taurus indicus) confinados e tratados com somatotrofina bovina recombinante (r-bST) / Metabolic and hormonal profile of feedlot Nellore bulls (Bos taurus indicus) and treated with recombinant bovine somatotropin (r-bST)

Avaliaram-se os efeitos da administração da somatotrofina bovina recombinante (r-bST) sobre os metabólitos sangüíneos de touros da raça Nelore de duas diferentes idades. Foram utilizados 16 touros, distribuídos em um delineamento fatorial 2 x 2 (idades: jovens e adultos; r-bST: 0 e 500mg) com quatro animais por tratamento. A idade média dos animais foi de 13,37 e 20,62 meses para jovens e adultos, respectivamente. Quatro animais por tratamento receberam, a cada 14 dias, solução salina ou 500mg de r-bST, totalizando nove aplicações por animal, em um período experimental de 120 dias. Os touros foram alimentados com silagem de milho e ração concentrada à base de farelo de milho e soja, duas vezes por dia, fornecidas em baias individuais. As coletas de sangue foram realizadas a cada três dias, para determinação da concentração dos metabólicos sangüíneos. Para análise estatística, foram compilados dados a intervalo de três aplicações, o que constituiu um período (período 1, 2 e 3). As concentrações de ácidos graxos não-esterificados (NEFA) foram analisadas semanalmente. As concentrações séricas de colesterol, proteína total e plasmáticas de glicose diferiram para os períodos e nos grupos de tratamentos (P<0,05). As concentrações de NEFA foram influenciadas pelas semanas de coleta (P<0,05), mas não pelo tratamento com ou sem r-bST (P>0,05).

This study was carried out to evaluate the effect of recombinant bovine somatotropin (r-bST) administration on profiles of blood metabolites of two different ages Nellore bulls. Sixteen bulls were randomly allotted in a factorial arrangement 2 x 2 (ages: youngs and adults; and r-bST dose: 0 and 500 mg) with four animals per treatment. The mean ages of the young and adult animals were 13.37 and 20.62 months, respectively. Four animals per treatment received saline solution or r-bST 500mg, every 14 days, totaling nine applications per animal during 120 days. The Bulls were fed corn silage and concentrated diet based on corn crumb and soybean meal, twice a day, in individual stalls. Blood was collected every three days for metabolic evaluation. The statistical analyses of the data were performed in three applications, considering three periods (1, 2 and 3). Non-esterified fatty acid (NEFA) concentrations were weekly analyzed. Serum cholesterol, total protein and glucose levels were affected either by period or the treatment (P<0.05). The NEFA was affected by weeks of collection (P<0.05) but not by r-bST treatment (P>0.05).

Biological & physiological aspects of action of insulin-like growth factor peptide family.

The insulin-like growth factor (IGF) is a complex system of peptide hormones (insulin-like growth factors of type 1 and 2, IGF-1 and IGF-2), cell surface receptors (insulin receptor, IR; insulin-like growth factor receptors of type 1 and 2, IGF-R1, IGF-R2) and circulating binding proteins (insulinlike growth factor binding proteins, IGF-BP 1-6). IGF-1 and -2 are mitogens that play a role in regulating cell proliferation, differentiation and apoptosis. Their effects are mediated through the IGF-R1 which initiates signaling cascades that result in regulation of a number of biological responses. IGF-R2, together with IGF-BPs is involved in binding, internalization and degradation of IGF-2. IGF proteins regulate cell proliferation in an interconnected action via autocrine, paracrine and endocrine regulatory mechanisms. Consequently, any perturbation in each level of the IGF signaling proteins has been shown to be implicated in development and progression of numerous cancer types. The most important single components in this processes are IGF ligands as well as IGF-R1 - when disturbed they act as oncogenes. It has been shown that: (i) high serum concentrations of IGF-1 and IGF-2 are associated with an increased risk of breast, prostate, colorectal and lung cancers; and (ii) IGF-R1 is commonly disturbed in many tumours (like gastric, lung, endometrial cancer) leading to a phenotype of anchorage-independent tumour growth. In contrast, IGF-R2 is considered to act as a tumour suppressor gene; it protects the cells from neoplastic impulses. Consistent with the IGFs autocrine/paracrine regulation of tumour growth, cancer treatment strategies interfering with IGF-R1 signaling have been developed, that may be useful in future diagnostic and therapeutic strategies.

Eixos hormonais na obesidade: causa ou efeito? / Hormonal axes in obesity: cause or effect?

Diversas alterações endócrinas são descritas na obesidade. O eixo corticotrófico encontra-se hiper-responsivo, com maior depuração dos hormônios e nível de cortisol normal. A caracterização do pseudo-Cushing é importante. A leptina parece ser um hormônio permissivo para o desencadeamento da puberdade. Em adultos, as gonadotrofinas são normais, hiperandrogenismo e hiperestrogenismo são encontrados. Nas mulheres, a resistência insulínica é central no desenvolvimento da síndrome dos ovários policísticos (SOP), associada a hiperandrogenemia ovariana. Nos obesos, GH geralmente é baixo e IGF1 normal. A função tireoidiana é habitualmente normal nos obesos.

Several endocrine changes have been described in the obesity state. The corticotropic axis is hyperresponsive and there is enhancement of hormonal clearance, but cortisol levels are within the normal range. It is important to characterize a pseudo-Cushing in obesity. Leptin seems to be a permissive hormone for the beginning of puberty. In adults, gonadotropines are normal, and hyperandrogenism and hyperestrogenism are found. In women, insulin resistance has a central role in polycystic ovarian syndrome (POS), which is associated to ovarian hyperandrogenemia. In obese subjects, growth hormone (GH) is generally low and IGF1 is normal. Thyroid function is commonly normal in obese subjects.

Understanding childhood depression.

Major depressive disorder in children is a severe and a chronically disabling disorder. This population appears to be a special group in terms of consequences of poor psychosocial and academic outcome and increased risk of substance abuse, and suicide. Studies have revealed several major findings in genetic, familial, psychological, and biological aspects of such depression, some of which have explored into the issue of its relationship with adult depression. Considerable advances have been made now in the area of childhood depression providing a better understanding of its nature. We review literature available on historical aspect, epidemiology, clinical characteristics, and aetiology of childhood depression.

Estimates of genetic parameters for Holstein cows for test-day yield traits with a random regression cubic spline model

Genetic parameters were estimated with restricted maximum likelihood for individual test-day milk, fat, and protein yields and somatic cell scores with a random regression cubic spline model. Test-day records of Holstein cows that calved from 1994 through early 1999 were obtained from Dairy Records Management Systems in Raleigh, North Carolina, for the analysis. Estimates of heritability for individual test-days and estimates of genetic and phenotypic correlations between test-days were obtained from estimates of variances and covariances from the cubic spline analysis. Estimates were calculated of genetic parameters for the averages of the test days within each of the ten 30-day test intervals. The model included herd test-day, age at first calving, and bovine somatropin treatment as fixed factors. Cubic splines were fitted for the overall lactation curve and for random additive genetic and permanent environmental effects, with five predetermined knots or four intervals between days 0, 50, 135, 220, and 305. Estimates of heritability for lactation one ranged from 0.10 to 0.15, 0.06 to 0.10, 0.09 to 0.15, and 0.02 to 0.06 for test-day one to test-day 10 for milk, fat, and protein yields and somatic cell scores, respectively. Estimates of heritability were greater in lactations two and three. Estimates of heritability increased over the course of the lactation. Estimates of genetic and phenotypic correlations were smaller for test-days further apart.