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- ItemAcesso aberto (Open Access)Os 50 anos de uso do hormônio adrenocorticotrófico (ACTH) no Tratamento da Síndrome de West: revisão de literatura e protocolo da UNIFESP(Liga Brasileira de Epilepsia (LBE), 2008-03-01) Gomes, Maria Durce Costa [UNIFESP]; Garzon, Eliana [UNIFESP]; Sakamoto, Américo Ceiki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)INTRODUCTION: It is extensively discussed in the literature the efficacy of ACTH in West Syndrome (WS) as well, dosage, best protocols and side effects. OBJECTIVE: Analyze and discuss the most recent and relevant publication related to ACTH in patients with WS. METHODOLOGY: Literature publication was selected from MEDLINE and PUBMED between 1997 to 2007 using the following key words: ACTH andWest Syndrome. RESULTS: 96 titles were referral at medline and 158 at pubmed. 22 were selected and previous studies with special relevance were also included. CONCLUSIONS: There are evidences that ACTH probably has efficacy for immediately control of spasms and hypsarrhythmia. There is no evidence about the efficacy of ACTH in long term concerning seizures control and prevent delayed developmental).
- ItemAcesso aberto (Open Access)The ACTH test in the diagnosis of hirsutism(Associação Paulista de Medicina - APM, 1997-04-01) Prata Lima, Marco Fábio [UNIFESP]; Nunes, Márcia Gaspar [UNIFESP]; Bonduki, Cláudio Emilio [UNIFESP]; Haidar, Mauro Abi [UNIFESP]; Lima, Geraldo Rodrigues [UNIFESP]; Baracat, Edmund Chada [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The ACTH test has been used to confirm the diagnosis of adrenal insufficiency and the classic and the non-classic adrenal hyperplasia due to the 3-HSD, 21 OH e 110H deficiencies. This article reviews the historical aspects of the use of ACTH in the diagnosis of hirsutism and points out its mains indications. In spite of new biological molecular advances in the diagnosis of adrenal enzymatic deficiencies, the use of the ACTH test can help the physician to predict both genothipus and fenothipus in populations with hyperandrogenic manifestations due to non-classical or late-onset congenital adrenal hyperplasia.
- ItemAcesso aberto (Open Access)Adenomas hipofisários produtores de ACTH: Aspectos neurocirúrgicos(Academia Brasileira de Neurologia - ABNEURO, 2002-03-01) Tella Jr, Oswaldo Inácio [UNIFESP]; Herculano, Marco Antonio; Delcelo, Rosana [UNIFESP]; Aguiar, Paulo Henrique; Universidade Federal de São Paulo (UNIFESP); Faculdade de Medicina de Jundiaí Disciplina de Neurocirurgia; Universidade de São Paulo (USP)We report our experience with 19 cases of ACTH secreting pituitary adenomas. They were microadenomas in 50% of the cases, coming with the typical picture of the Cushing syndrome. The ACTH adenoma associated with other types of hormones tend to show visual alterations. The treatment is often surgical using the transsphenoidal approach. The results were satisfactory in most of the cases. For those in which surgical cure was not reached, radiotherapy was indicated.
- ItemSomente MetadadadosAdrenocorticotropin-producing pituitary carcinoma with expression of c-erbB-2 and high PCNA index: A comparative study with pituitary adenomas and normal pituitary tissues(Humana Press Inc, 1998-03-01) Nose-Alberti, V; Mesquita, MIS; Martin, L. C.; Kayath, M. J.; Universidade Federal de São Paulo (UNIFESP)Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing's disease resulting from a pituitary carcinoma in a ZZ-yr-old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing's disease (n = 52), other pituitary adenomas (n = 292), and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis. C-erbB-2 staining was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular immunohistological type preferentially expressed this protein. in normal pituitary tissues, 10% of the cells expressed cytoplasmic c-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4 +/- 1.9% vs 1.7 +/- 1.5% in noninvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). the PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p(21ras) was negative in the carcinoma and liver metastasis. We suggest that the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.
- ItemAcesso aberto (Open Access)Atividade Enzimática da 21-Hidroxilase e da 3beta-Hidroxiesteróide Desidrogenase em Mulheres Hirsutas com e sem Anovulação Crônica(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2000-10-01) Prata Lima, Marco Fábio [UNIFESP]; Baracat, Edmund Chada [UNIFESP]; Lima, Geraldo Rodrigues de [UNIFESP]; Pardini, Dolores Perovano [UNIFESP]; Silva, Cléber Sérgio da; Caetano, Marcos Roberto; Faculdade de Medicina do Triângulo Mineiro Disciplina de Ginecologia e Obstetrícia Setor de Ginecologia Endócrina e Climatério; Universidade Federal de São Paulo (UNIFESP)Purpose: to test the adrenal function by a potent stimulus to its reticular layer verifying 3beta-hydroxysteroid dehy-drogenase (3beta-HSD) and 21-hydroxylase (21OH) enzymatic activities. Methods: plasma concentrations of 17alphaOH-pregneno-lone, 17alphaOH-progesterone, cortisol, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (SDHEA) and free testosterone were determined in 39 women, 13 of whom were normal (2 of them used in a pilot study) and 26 had idiopathic hirsutism, 0, 12 and 24 h after injection of ACTH-depot. Results: among hirsute women, we identified different responses that could diagnose any blockage in the steroid pathways leading to the diagnosis of a mild/moderate decreased adrenal function. The 17alphaOH-pregnenolone concentrations varied from 2.0 to 24.6 ng/mL, cortisol values increased from 2.1 to 45.3 and 38.4 mug/dL, 17alphaOH-progesterone levels varied from 50.7 to 346 and 218 ng/mL and progesterone increased from 0.3 to 4.4 and 2.2 ng/mL. Among the reticular layer hormones a rise of SDHEA from 274.7 to 495.5 and 505.8 mg/dL, and of androsterone from 1.1 to 4.0 and 4.5 ng/mL was observed, the levels of free testosterone increased from 1.3 to 1.8 and 2.7 pg/mL and the DHEA levels from 2.4 to 4.7 and 8.5 ng/mL. One patient showed 3beta-HSD deficiency and two others a possible 21OH deficiency. Conclusions: these findings suggest that the ACTH-depot test could be used to exclude the adrenal gland as the possible source of hyperandrogenism in women with idiopathic hirsutism.
- ItemAcesso aberto (Open Access)Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with cushing s disease(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-10-01) Correa-Silva, Silvia R. [UNIFESP]; Nascif, Sérgio O. [UNIFESP]; Silva, Marcos R. [UNIFESP]; Molica, Patrícia [UNIFESP]; Lengyel, Ana Maria Judith [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)GH responses to ghrelin, GHRP-6, and GHRH in Cushing s disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (mg/L; mean ± SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 ± 4.5; 3.8 ± 1.6, and 0.6 ± 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75%), but GH responses did not change (7.0 ± 2.0; 3.1 ± 0.8; 0.9 ± 0.2, respectively). After treatment, there was a significant reduction in cortisol (mg/dL) responses to ghrelin (before: 30.6 ± 5.2; after: 24.2 ± 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 ± 69.9; GHRP-6: 199.8 ± 88.8) and after treatment (ghrelin: 159.7 ± 40.3; GHRP-6: 227 ± 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.
- ItemSomente MetadadadosEffects of ghrelin, GH-releasing peptide-6 (GHRP-6) and GHRH on GH, ACTH and cortisol release in hyperthyroidism before and after treatment(Springer, 2010-12-01) Molica, Patricia [UNIFESP]; Nascif, Sergio Oliva [UNIFESP]; Correa-Silva, Silvia Regina [UNIFESP]; Paiva Cunha de Sa, Larissa Bianca [UNIFESP]; Henriques Vieira, Jose Gilberto [UNIFESP]; Lengyel, Ana Maria Judith [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In thyrotoxicosis GH responses to stimuli are diminished and the hypothalamic-pituitary-adrenal axis is hyperactive. There are no data on ghrelin or GHRP-6-induced GH, ACTH and cortisol release in treated hyperthyroidism. We, therefore, evaluated these responses in 10 thyrotoxic patients before treatment and in 7 of them after treatment. GHRH-induced GH release was also studied. Peak GH (mu g/L; mean +/- A SE) values after ghrelin (22.6 +/- A 3.9), GHRP-6 (13.8 +/- A 2.3) and GHRH (4.9 +/- A 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 +/- A 19.3; GHRP-6: 25.4 +/- A 2.7; GHRH: 12.2 +/- A 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 +/- A 4.7; GHRP-6: 15.6 +/- A 3.6; GHRH: 7.4 +/- A 2.3), although GH responses to all peptides increased in similar to 50% of the patients. in thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 +/- A 26.3) than those of controls (54.9 +/- A 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 +/- A 9.0; controls: 31.3 +/- A 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 +/- A 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 +/- A 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 +/- A 4.2), with no further changes. in hyperthyroidism before treatment, peak cortisol (mu g/dL) responses to ghrelin (18.2 +/- A 1.2) and GHRP-6 (15.9 +/- A 1.4) were comparable to controls (ghrelin: 16.4 +/- A 1.6; GHRP-6: 13.5 +/- A 0.9) and no changes were seen after treatment. Our results suggest that the pathways of GH release after ghrelin/GHRP-6 and GHRH are similarly affected by thyroid hormone excess and hypothalamic mechanisms of ACTH release modulated by ghrelin/GHSs may be activated in this situation.
- ItemSomente MetadadadosGH-releasing peptide (GHRP-6)-induced ACTH release in patients with Addison's disease: Effect of glucocorticoid withdrawal(Editrice Kurtis S R L, 2003-02-01) Martins, Manoel Ricardo Alves [UNIFESP]; Pinto, ACAR [UNIFESP]; Brunner, E. [UNIFESP]; Silva, MRD [UNIFESP]; Lengyel, AMJ [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)GH releasing peptide (GHRP-6) is a synthetic hexapeptide with potent GH releasing activity both in man and in animals. This peptide is also able to stimulate ACTH and cortisol (F) release. It has been suggested that the ACTH responsiveness to GHRP-6 is modulated by circulating glucocorticoid levels. To further clarify this hypothesis, we studied the effect of GHRP-6 (1 ug/kg, iv) on ACTH and F release in patients with Addison's disease (no.=6) during replacement therapy and after 72 h of glucocorticoid withdrawal. Seven controls were also submitted to a single GHRP-6 test. In control subjects, ACTH values (pmol/l; mean+/-SE) increased from 2.9+/-0.8 to 4.7+/-1.4 (peak). AUC (pmol.min/l) values were 170.3+/-48.8. F (nmol/l) values increased from 257.0+/-42.9 to 367.0+/-50.8. In patients with Addison's disease there was an increase in ACTH levels from 38.1+/-7.1 to 174.9+/-79.4 after GHRP-6 administration. AUC values were 5490.4+/-2269.1. After 72 h withdrawal of glucocorticoid, there was an increase in basal ACTH values (1191.2+/-97.3), and a trend toward an increase in ACTH levels after GHRP-6 (p=0.053). Patients with Addison's disease on therapy showed a significantly higher ACTH response to GHRP-6 when compared to controls. Our results show that in patients with Addison's disease on replacement there is an increased ACTH release after GHRP-6 administration, compared to controls. After 72 h glucocorticoid withdrawal, this enhanced responsiveness is not maintained. Our data suggest that circulating glucocorticoids modulate GHRP-6-induced ACTH release and that multiple mechanisms may be involved in this process. (C) 2003, Editrice Kurtis.
- ItemSomente MetadadadosGhrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis(Springer, 2009-12-01) Nascif, Sergio Oliva [UNIFESP]; Molica, Patricia [UNIFESP]; Correa-Silva, Silvia Regina [UNIFESP]; Silva, Marcos Roberto [UNIFESP]; Lengyel, Ana-Maria Judith [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid patients and in 9 controls. Mean basal cortisol (mu g/dl) and ACTH (pg/ml) levels were higher in hyperthyroidism (cortisol: 10.7 +/- A 0.7; ACTH: 21.5 +/- A 2.9) compared to controls (cortisol: 8.1 +/- A 0.7; ACTH: 13.5 +/- A 1.8). in thyrotoxicosis a dagger AUC cortisol values (mu g/dl.90 min) after ghrelin (484 +/- A 80) and GHRP-6 (115 +/- A 63) were similar to controls (ghrelin: 524 +/- A 107; GHRP-6: 192 +/- A 73). A significant increase in a dagger AUC ACTH (pg/ml.90 min) after ghrelin was observed in thyrotoxicosis (4,189 +/- A 1,202) compared to controls (1,499 +/- A 338). a dagger AUC ACTH values after GHRP-6 were also higher, although not significantly (patients: 927 +/- A 330; controls: 539 +/- A 237). in summary, our results suggest that ghrelin-mediated pathways of ACTH release might be activated by thyroid hormone excess, but adrenocortical reserve is maintained.
- ItemSomente MetadadadosGHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: Comparison with DDAVP(Editrice Kurtis S R L, 2003-03-01) Oliveira, JHA [UNIFESP]; Vieira, Jose Gilberto Henriques [UNIFESP]; Abucham, J. [UNIFESP]; Lengyel, AMJ [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Med DiagnostIt has been shown that hexarelin stimulates ACTH and cortisol secretion in patients with Cushing's disease. The ACTH release induced by this peptide is 7-fold greater than that obtained by hCRH. The mechanism of action of hexarelin on the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although controversial, there is evidence that it might be mediated by arginine vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol releasing effects of GHRP-6 in patients with Cushing's disease and to compare them with those obtained with DDAVP administration. We studied 10 patients with Cushing's disease (8 female, 2 male; age: 36.7+/-4.2 yr), 9 with microadenomas, who were submitted to both GHRP-6 (2mug/kg iv) and DDAVP (10 mug iv) in bolus administration on 2 separate occasions. ACTH was measured by immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was able to increase significantly both ACTH (pmol/l, mean +/-SE; basal: 15.5+/-1.7 vs peak: 45.1+/-9.3) and cortisol values (nmol/l, basal: 583.0+/-90.8 vs peak: 1013.4+/-194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(-1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration there was a significant increase in ACTH (basal: 13.0+/-1.4 vs peak: 50.5+/-16.2) and cortisol levels (basal: 572.5+/-112.7 vs peak: 860.5+/-102.8). AUC values for ACTH and cortisol were 1627.6+/-639.8 and 18364.7+/-5661.4, respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ significantly (peak: 45.1+/-9.3 vs 50.5+/-16.2; AUC: 1235.4+/-424.8 vs 1627.6+/-639.8). There was a significant positive correlation between peak cortisol values after GHRP-6 and DDAVP administration (r=0.87, p=0.001). Our results show that GHRP-6 is able to stimulate ACTH and cortisol release in patients with Cushing's disease. These responses are similar to those obtained after DDAVP injection. These findings could suggest the hypothesis that both peptides act by similar mechanisms, either at hypothalamic or pituitary level. (C) 2003, Editrice Kurtis.
- ItemSomente MetadadadosIncreased ACTH and corticosterone secretion induced by different methods of paradoxical sleep deprivation(Blackwell Science Ltd, 1998-12-01) Suchecki, Deborah [UNIFESP]; Lobo, Leticia Leite [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The methods used to induce paradoxical sleep (PS) deprivation are believed to be stressful. in the present study, two methods were compared in regard to their ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. Animals were placed on multiple large (MLP) or small (MSP) platforms or on single large (SLP) or small (SSP) platforms and blood sampled at the end of a 4-day period of PS deprivation (experiment 1) or on Days 1 (short-term) and 1 (long-term) of PS deprivation (experiment 2). ACTH and corticosterone (CORT) levels were determined by RIA. the results of experiment 1 showed that all experimental animals presented increased ACTH response, compared to controls. CORT levels, however, were only elevated in MSP animals, suggesting increased adrenal sensitivity. Experiment 2 showed that ACTH levels of MSP animals were higher than MLP and SSP animals, and that animals placed on the multiple platform tanks showed the highest ACTH levels on Day 4 of manipulation. CORT levels were elevated in the animals kept over small platforms. and these levels where higher on Day 1 than basal and further elevated on Day 4 of PS deprivation. These results indicate that the multiple platform technique induces a distinct activation of the I-IPA axis, and that PS deprivation may act as an additional stressor.
- ItemAcesso aberto (Open Access)More than hormones: Sex differences in cardiovascular parameters after sleep loss in rats(Elsevier B.V., 2013-07-01) Matos, Gabriela de [UNIFESP]; Tenorio, Neuli Maria [UNIFESP]; Bergamaschi, Cassia Toledo [UNIFESP]; Campos, Ruy Ribeiro [UNIFESP]; Cintra, Fátima Dumas [UNIFESP]; Tufik, Sergio [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Although the influence of sex on sleep pattern and cardiovascular parameters is well known, knowledge regarding the effects of sleep loss on heart responses in both sexes is scarce. the present study investigated the effects of paradoxical sleep deprivation (PSD) and chronic sleep restriction (SR) on cardiovascular parameters and adrenocorticotropic hormone (ACTH) levels in male and female rats. Both groups were randomly assigned to PSD for 96 h, SR for 21 days or home-cage control. Mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity (bradycardia and tachycardia responses) and ACTH levels were evaluated. the results showed that PSD induced a significant increase in HR and ACTH levels in both sexes, although male rats presented higher levels of ACTH hormone compared to females. in addition to sex-specific responses, PSD decreased the tachycardia only in male rats. SR, induced a significant increase in MAP and decrease in bradycardia in both sexes. Male rats were more affected by sleep deprivation protocols than females for MAP, bradycardia response, and ACTH levels. the results showed that the effects of sleep loss on cardiovascular parameters are associated with the protocol of sleep deprivation and that sex can modulate these effects. We suggested this experimental model as a suitable tool for further investigations of the relationship between cardiovascular parameters and sleep. (C) 2013 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosNeuroendocrine effects of quetiapine in healthy volunteers(Cambridge Univ Press, 2005-03-01) Guerra, Alexandro de Borja Gonçalves [UNIFESP]; Castel, Saulo [UNIFESP]; Benedito-Silva, Ana Amélia [UNIFESP]; Calil, Helena Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The present study measured prolactin, cortisol, ACTH and growth hormone in healthy male volunteers following an acute oral administration of quetiapine, an atypical antipsychotic with high affinity for H, and moderate affinity for sigma, sigma(1), 5-HT2, alpha(2) and D-2 receptors. Fifteen male volunteers entered this randomized double-blind, cross-over, placebo-controlled study. Blood samples were drawn every 30 min from 09:00 hours to 13:00 hours. the first samples were drawn immediately before the administration of 150 mg quetiapine or placebo. Mean results for each hormone and ANOVA for repeated measures were performed. the area under the curve (AUC) hormonal values were calculated and compared by paired t test. the ANOVA showed an increase of prolactin after quetiapine administration from time 60 min up to the end of the observation period. Cortisol decreased after quetiapine administration from time 150 min to time 240 min. ACTH secretion showed no difference compared to placebo. There was a late increase in growth hormone secretion, significant in comparison with placebo only at time 210 min. the AUC values were statistically different for prolactin and cortisol compared to placebo. A single dose of quetiapine (150 mg) increased prolactin secretion probably due to a transiently high D, receptor occupancy at the anterior pituitary. Cortisol secretion decreased as was expected from quetiapine's pharmacodynamic profile. the lack of response of ACTH might be, at least in part, explained by the low hormonal assay sensitivity. the late growth hormone increase might have been due to quetiapine's antagonism of H, receptors.
- ItemSomente MetadadadosA panic attack-like unusual stress reaction(Elsevier B.V., 2008-11-01) Schenberg, Luiz Carlos; Reis, Adelina Martha dos; Ferreira Povoa, Raner Miguel; Tufik, Sergio [UNIFESP]; Silva, Sara Regina; Univ Fed Espirito Santo; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP)Ever since the seminal studies of Hans Selye, activation of hypothalamus-pituitary-adrenal (HPA) axis is emblematic of stress. Consequently, the lack of HPA axis responses following the undisputable psychological stress of a panic attack stands out as one of the most intriguing findings of contemporary psychiatry. On the other hand, the defensive behaviors and aversive emotions produced by stimulation of the dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attacks. Therefore, we examined whether the plasma levels of 'stress hormones' corticotropin and prolactin show any change following the DPAG-evoked freezing and flight behaviors of the rat. Rats bearing an electrode into the DPAG and an intra-atrial catheter were stimulated at 9:00 a.m., 18-24 h after the catheter implantation. Blood samples were withdrawn just before 1-min stimulation of DPAG, immediately after (5 or 15 min) and throughout 3 to 27 h following stimulation. in another experiment, samples were withdrawn either before or following a prolonged stimulation (5 min) of the DPAG with flight threshold intensity. Hormones were measured by either chemiluminescent or double-antibody immunoassays. Hormone plasma levels following freezing and flight behaviors were compared to those of resting or restraint-stressed rats. Data show that stress hormones remain unaltered following the DPAG-evoked defensive behaviors. Not even the 5-min stimulation of DPAG with the flight threshold intensity changed corticotropin plasma levels significantly. As far as we known, this is the first demonstration of the lack of stress hormone responses following the intense emotional arousal and physical exertion of a fear-like behavior in rats. Data add new evidence of DPAG involvement in spontaneous panic attacks. (c) 2008 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosProliferative signaling initiated in ACTH receptors(Assoc Bras Divulg Cientifica, 2000-10-01) Lotfi, Claudimara Ferini Pacicco [UNIFESP]; Lepique, Ana Paula; Forti, Fabio Luis; Schwindt, Telma Tiemi [UNIFESP]; Eichler, C. B.; Santos, M. O.; Rebustini, I. T.; Hajj, GNM; Juliano, Luiz [UNIFESP]; Armelin, Hugo Aguirre; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G(0)-->G(1)-->S transition in the adrenal cell cycle. FGF? elicits a strong mitogenic response in G(0)/G(1)-arrested Y1 adrenocortical cells, that includes a) rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK) (2 to 10 min), b) transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min), c) induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d) onset of DNA synthesis stimulation within s h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G(1) phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression, c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.
- ItemAcesso aberto (Open Access)Terapia de reposição hormonal no hipopituitarismo(Sociedade Brasileira de Endocrinologia e Metabologia, 2003-08-01) Abucham, Julio [UNIFESP]; Vieira, Teresa C. Alfinito [UNIFESP]; Barbosa, Erika Ribeiro [UNIFESP]; Ribeiro, Rogério Silicani [UNIFESP]; Martins, Manoel R. Alves [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)This article brings an updated review of hypopituitarism with emphasis in hormone replacement therapy. The physiological basis of hormone replacement therapy and practical aspects of treating hypopituitary patients were both taken into account to provide a rational strategy for treatment. The review is organized by individual pituitary hormone deficiency and covers epidemiology, etiology, clinical presentation, and diagnosis of hypopituitarism, as well as the most relevant hormone preparations currently available for treating each hormone deficiency. Practical guidelines to hormone dosing, routes of administration, side effects and clinical and laboratory monitoring during the entire lifespan are given for each individual hormone replacement therapy: growth hormone in GH-deficient children and adults, thyroid hormone in central hypothyroidism, glucocorticoid in central hypoadrenalism, vasopressin analogs in diabetes insipidus, sex hormones in man and women from puberty to senescence, and gonadotropins for treating infertility. In addition to the literature review, we took into account our own experience of more than two decades in investigating, diagnosing, and treating hypopituitary patients at the Universidade Federal de São Paulo (UNIFESP).