Corticosterone does not change open elevated plus maze-induced antinociception in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Endocrine changes in cerebrospinal fluid, pituitary effluent, and peripheral plasma of anesthetized ponies

Objective - To investigate the effects of inhalation and total IV anesthesia on pituitary-adrenal activity in ponies. Animals - 9 healthy ponies: 5 geldings and 4 mares. Procedure - Catheters were placed in the cavernous sinus below the pituitary gland and in the subarachnoid space via the lumbosacral space. After 72 hours, administration of acepromazine was followed by induction of anesthesia with thiopentone and maintenance with halothane (halothane protocol), or for the IV protocol, anesthesia induction with detomidine and ketamine was followed by maintenance with IV infusion of a detomidine-ketamine-guaifenesin combination. Arterial blood pressure and gas tensions were measured throughout anesthesia. Peptide and catecholamine concentrations were measured in pituitary effluent, peripheral plasma, and CSF. Peripheral plasma cortisol, glucose, and lactate concentrations also were measured. Results - Intravenous anesthesia caused less cardiorespiratory depression than did halothane. ACTH, metenkephalin, arginine vasopressin, and norepinephrine pituitary effluent and peripheral plasma concentrations were higher during halothane anesthesia, with little change during intravenous anesthesia. Pituitary effluent plasma β-endorphin and peripheral plasma cortisol concentrations increased during halothane anesthesia only. Dynorphin concentrations did not change in either group. Hyperglycemia developed during intravenous anesthesia only Minimal changes occurred in CSF hormonal concentrations during anesthesia. Conclusion - The pituitary gland has a major role in maintaining circulating peptides during anesthesia. Compared with halothane, IV anesthesia appeared to suppress pituitary secretion.

Morphology of testis and epididymis in an ethanol-drinking rat strain (UChA and UChB)

The objective of the present study was to analyze the prospective alterations of the testis and epididymis in a defined strain of alcoholic rats in order to contribute to our understanding of the effects of chronic alcoholism on reproduction. The testis and epididymis of the animals were submitted to morphological analysis by macroscopy, light microscopy and electron microscopy and to morphometric analysis. The UCh rats showed atrophy of the epithelium and reduction of testis and epididymis weight, liver hypertrophy and fat infiltration and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the weight and in the epithelium of the testis and epididymis and in the hypothalamus-pituitary axis of the UCh rats.

Morphology of the ventral lobe of the prostate and seminal vesicles in an ethanol-drinking strain of rats (UChA and UChB)

Chronic alcoholism alters reproduction and therefore may be responsible for alterations of prostate and seminal vesicles, which are the subject of this analysis in UCh ethanol-drinking rats. The prostate and seminal vesicles of 20 animals were submitted to macroscopic, light microscopy, electron microscopy and morphometric analysis. The UCh rats showed atrophy of the epithelium and reduction of the weight of the prostate and seminal vesicle, liver hypertrophy and fat infiltration and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the weight and in the epithelium of prostate and seminal vesicles and hypothalamus-pituitary axis of UCh rats.

Morphology of the vas deferens in an ethanol-drinking strain of rats (UChA and UChB)

Chronic alcoholism alters reproduction and therefore may be responsible for alterations of vas deferens, which are the subject of this analysis in UCh ethanol-drinking rats. The proximal and distal segments of the vas deferens of 20 animals were submitted to macroscopic, light microscopy, electron microscopy and morphometric analysis. The UCh rats showed atrophy of the epithelium of the vas deferens and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the epithelium of the vas deferens and hypothalamus-pituitary axis of UCh rats.

Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate. © 2007 by The University of Chicago. All rights reserved.

Cortisol response to acute stress in jundiá Rhamdia quelen acutely exposed to sub-lethal concentrations of agrichemicals

Exposure to agrichemicals can have deleterious effects on fish, such as disruption of the hypothalamus-pituitary-inter-renal axis (HPI) that could impair the ability of fish to respond to stressors. In this study, fingerlings of the teleost jundiá (Rhamdia quelen) were used to investigate the effects of the commonly used agrichemicals on the fish response to stress. Five common agrichemicals were tested: the fungicide - tebuconazole, the insecticide - methyl-parathion, and the herbicides - atrazine, atrazine + simazine, and glyphosate. Control fishes were not exposed to agrichemicals and standard stressors. In treatments 2-4, the fishes were exposed to sub-lethal concentrations (16.6%, 33.3%, and 50% of the LC50) of each agrichemical for 96 h, and at the end of this period, were subjected to an acute stress-handling stimulus by chasing them with a pen net. In treatments 5-7 (16.6%, 33.3%, and 50% of the LC50), the fishes were exposed to the same concentrations of the agrichemicals without stress stimulus. Treatment 8 consisted of jundiás not exposed to agrichemicals, but was subjected to an acute stress-handling stimulus. Jundiás exposed to methyl-parathion, atrazine + simazine, and glyphosate presented a decreased capacity in exhibiting an adequate response to cope with stress and in maintaining the homeostasis, with cortisol level lower than that in the control fish (P < 0.01). In conclusion, the results of this study clearly demonstrate that the acute exposure to sub-lethal concentrations of methyl-parathion, atrazine + simazine, and glyphosate exert a deleterious effect on the cortisol response to an additional acute stressor in the jundiá fingerlings. © 2008 Elsevier Inc. All rights reserved.

Mixed germ cell tumor of the pituitary-hypothalamic region presenting as craniopharyngioma: Case report and review of the literature

Craniopharyngiomas and germ cell tumors (GCT) may affect the pituitary-hypothalamic region during childhood. Although different in origin, their clinical and radiological features may be similar. In this article we present a 5-year-old girl with clinical and radiological findings (computer tomography calcification) that were initially considered as craniopharyngioma. However clinical outcome, blood and cerebral spinal fluid tumoral markers, and results from anatomopathology and immunohistochemistry disclosed a mixed GCT. This case report highlights that some clinical features and radiological findings of pituitary-hypothalamic tumors may be misdiagnosed as craniopharyngioma mainly when there is a mature teratoma with cartilaginous tissue differentiation. Copyright© ABE&M.

Avaliação dos níveis séricos de cortisol e de hidroepiandrosterona em pacientes com malária por Plasmodium falciparum não-complicada

O objetivo desta pesquisa foi avaliar o comportamento dos níveis séricos de cortisol e dehidroepiandrosterona (DHEA) em pacientes com malária por Plasmodium falciparum. Como o cortisol apresenta um efeito imunossupressor e o DHEA um efeito imunoestimulador, estudou- se a correlação entre os níveis destes esteróides e a condição clínica do paciente de malária. A amostra constou de 24 pacientes com malária por P. falciparum não-complicada, sendo 18 do sexo masculino e 6 do sexo feminino, com idade variando de 15 a 47 anos, 12 primoinfectados e 12 multi-infectados, provenientes de área endêmica de malária da Amazônia. Coletaram-se amostras diárias de sangue de 20 em 20 minutos no pré-tratamento (D0), 24 horas após o início da medicação (D1) e no 8º dia de acompanhamento (D7), quando o paciente já se encontrava assintomático. Todos os pacientes apresentavam parasitemia negativa em D7. Dosaram-se: os níveis séricos de cortisol em D0, D1 e D7; DHEA em D0 e D7; os níveis de anticorpos totais IgG anti-P. falciparum, anti-P. vivax, e anticorpos IgM anti-P. falciparum em D0. Comparam-se os níveis séricos de cortisol dos três dias, concluindo-se que os níveis de cortisol eram significativamente mais elevados em D0 do que nos outros dias. Foram correlacionados os níveis de cortisol com a parasitemia, obtendo-se como significativas as correlações entre cortisol D0 e parasitemia D1, assim como cortisol D1 com parasitemia D1, levando-se a deduzir que o cortisol pode interferir na resposta inicial à terapêutica de pacientes com malária por P. falciparum. O cortisol foi correlacionado com a temperatura, tempo de evolução da doença, níveis de anticorpos IgG anti-P. falciparum, não se obtendo resultados estatisticamente significativos, levando a inferir que a temperatura não interfere nos níveis de cortisol e o mesmo não interfere nos níveis de anticorpos, e não apresenta variações importantes com o tempo de evolução da doença. Os níveis de DHEA em D0, foram significativamente mais elevados do que em D7, apesar dos pacientes estarem sintomáticos há mais de um dia, já que um estímulo mantido do eixo hipotálamo-hipófise-adrenal (HPA) leva a uma diminuição deste esteróide. O DHEA foi correlacionado com a parasitemia obtendo-se um resultado significativo na correlação DHEA D0 com parasitemia D1. A correlação entre cortisol e DHEA em D0 não foi significativa (p = 0,057), porém este resultado leva a crer que o DHEA acompanha o aumento dos níveis de cortisol. Obteve-se uma correlação negativa entre DHEA e tempo de evolução de doença, apesar destes níveis estarem aumentados no pré-tratamento. Calculou-se a correlação parcial entre cortisol, DHEA e temperatura, concluindo-se que a temperatura interfere positivamente na correlação cortisol e DHEA. Uma vez que a febre reflete o momento em que ocorre a lise das hemácias secundária a esquizogonia, provavelmente esta lise com conseqüente liberação de citocinas serve como um fator agudizador da estimulação do eixo HPA, sugerindo que a liberação dos dois hormônios apresenta mecanismo comum. A correlação entre DHEA e anticorpos não foi significativa, portanto o DHEA não deve interferir na produção de anticorpos de pacientes com malária por P. falciparum.

Validação fisiológica da dosagem dos metabólitos de glucocorticóides em fezes de Papagaio-verdadeiro (Amazona aestiva)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação adrenocortical, tireoideana e do estresse oxidativo de cães naturalmente infectados por Ehrlichia canis

Pós-graduação em Medicina Veterinária - FCAV

Comportamento materno e câncer de bexiga urinária: implicações da modulação de eixos hormonais e receptores de esteroides na fisiopatologia de lesões neoplásicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Plasma corticosterone levels in mouse models of pain

Background: Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs. Aims/Methods: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone. Results: Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice. Conclusion: Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.

Effects of thyroid status on NEI concentration in specific brain areas related to reproduction during the estrous cycle

We previously showed that short-term hypo- and hyperthyroidism induce changes in neuropeptide glutamic-acid-isoleucine-amide (NEI) concentrations in discrete brain areas in male rats. To investigate the possible effects of hypo- and hyperthyroidism on NEI concentrations mainly in hypothalamic areas related to reproduction and behavior, female rats were sacrificed at different days of the estrous cycle. Circulating luteinizing hormone (LH), estradiol and progesterone concentrations were measured in control, hypothyroid (hypoT, treated with PTU during 7-9 days) and hyperthyroid (hyperT, l-T4 during 4-7 days) animals. Both treatments blunted the LH surge. Hypo- and hyperthyroidism increased estradiol concentrations during proestrus afternoon (P-PM), although hypoT rats showed lower values compared to control during proestrus morning (P-AM). Progesterone levels were higher in all groups at P-PM and in the hyperT during diestrus morning (D2). NEI concentrations were lower in hypoT rats during the estrous cycle except in estrus (E) in the peduncular part of the lateral hypothalamus (PLH). They were also reduced by both treatments in the perifornical part of the lateral hypothalamus (PeFLH) during P-PM. Hypothyroidism led to higher NEI concentrations during P-PM in the organum vasculosum of the lamina terminalis and anteroventral periventricular nucleus (OVLT+AVPV). The present results indicate that NEI concentration is regulated in a complex manner by hypo- and hyperthyroidism in the different areas studied, suggesting a correlation between NEI values and the variations of gonadal steroid levels during estrous cycle. These changes could be, in part, responsible for the alterations observed in the hypothalamic-pituitary-gonadal axis in these pathologies.

Stress hormones in patients with posttraumatic stress disorder caused by myocardial infarction and role of comorbid depression

Chronic posttraumatic stress disorder (PTSD) has been associated with perturbed hypothalamic-pituitary-adrenal (HPA) axis function and a hyperadrenergic state. We hypothesized that patients with PTSD attributable to myocardial infarction (MI) would show peripheral hypocortisolemia and increased norepinephrine levels, whereby taking into account that depressive symptoms would affect this relationship.