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1.
Hypertension ; 74(5): 1152-1159, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31564164

RESUMO

Microarray comparison of the transcriptomes of human adrenal zona glomerulosa (ZG) and zona fasciculata found several ZG-specific genes that negatively regulate aldosterone secretion. The third and most significantly upregulated ZG-gene (19.9-fold compared with zona fasciculata, P=6.58×10-24) was ANO4, a putative Ca2+-activated chloride channel. We have investigated the role of ANO4 in human adrenal, and whether it functions like the prototype anoctamin, ANO1. We evaluated ANO4 mRNA and protein expression in human adrenal by qPCR and immunohistochemistry, compared the effects of ANO4 and ANO1 overexpression on baseline and stimulated aldosterone secretion and cell proliferation in H295R cells, and analyzed ANO4 activity as a Ca2+-activated chloride channel in comparison with other anoctamins by a fluorescence-based functional assay. The expression of ANO4 in ZG was confirmed by qPCR as 23.21-fold upregulated compared with zona fasciculata (n=18; P=4.93×10-7). Immunohistochemistry found cytoplasmic, ZG-selective expression of ANO4 (anoctamin 4) protein. ANO4 overexpression in H295R cells attenuated calcium-mediated aldosterone secretion and cell proliferation in comparison to controls. The latter effects were in a different direction to those of ANO1. The functional assay showed that, in contrast to ANO1, ANO4 expression results in low levels of calcium-dependent anion transport. In conclusion, ANO4 is one of the most highly expressed genes in ZG. It attenuates stimulated aldosterone secretion and cell proliferation. Although belonging to a family of Ca2+-activated chloride channels, it does not generate significant plasma membrane chloride channel activity.


Assuntos
Aldosterona/biossíntese , Anoctaminas/genética , Regulação da Expressão Gênica , Hiperaldosteronismo/genética , Hipertensão/fisiopatologia , Transdução de Sinais/genética , Zona Glomerulosa/metabolismo , Córtex Suprarrenal/citologia , Córtex Suprarrenal/metabolismo , Córtex Suprarrenal/patologia , Análise de Variância , Comunicação Celular/genética , Proliferação de Células , Células Cultivadas , Imunofluorescência , Humanos , Hiperaldosteronismo/patologia , Hipertensão/etiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise Serial de Tecidos , Técnicas de Cultura de Tecidos , Transcriptoma/genética , Regulação para Cima , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Glomerulosa/patologia
2.
Bull Exp Biol Med ; 166(2): 283-286, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30488200

RESUMO

We studied secretory activity of adrenal zona fasciculata cells in pubertal rats exposed to low doses of endocrine disrupter DDT during prenatal and postnatal periods and only during postnatal period. In exposed animals, circulatory disturbances leading to degeneration and necrosis of cells as well as regeneration foci were revealed in the outer zona fasciculata. In rats exposed to DDT during the prenatal and postnatal periods, compensatory increase in secretory activity of cells due to increase in mitochondria content was noted in the inner zona fasciculata, which determined elevated serum concentration of corticosterone. In rats exposed to DDT only during the postnatal development, functional activity of zona fasciculata cells was suppressed, which attested to delayed upregulation of secretion.


Assuntos
Corticosterona/sangue , DDT/toxicidade , Disruptores Endócrinos/toxicidade , Mitocôndrias/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Zona Fasciculada/efeitos dos fármacos , Animais , Esquema de Medicação , Feminino , Lactação/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Masculino , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Fatores de Tempo , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia
3.
Medicina (Kaunas) ; 54(5)2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30463213

RESUMO

Background and objectives: Energy drinks are popular non-alcoholic beverages. They are consumed in large amounts, mainly by active, young people. Although they are easily accessible and marketed as safe, numerous cases of adverse effects have been published, including cardiac arrest, arrythmias, acute hepatitis, and renal failure. The aim of the current study is the assessment of energy drink influence on the histological structure of adrenal cortex in rats. Material and Methods: 15 male young Wistar rats were equally divided into three groups: control (C), experimental (E) and reversibility control (RC). C group received water and standard rodent food ad libitum while both E and RC groups had additionally unlimited access to energy drinks. C and E groups were decapitated after 8 weeks and RC was given another 8 weeks without energy drinks. Adrenal glands were embedded in paraffin blocks and 5 µm slides were prepared and stained according to standard H&E and Masson's trichrome protocols. Additionally, immunohistochemical stainings against Ki-67, p53, CTGF and caspase-3 were prepared. Results: Decreased vacuolization and numerous pyknotic nuclei were noted in E and RC groups. Overexpression of caspase-3 was noted both subcapsular in zona glomerulosa and along sinusoids in zona fasciculata. Increased collagen deposition in zona glomerulosa and zona fasciculata of E and RC was observed. Insular and irregular overexpression of CTGF was noted. The overall picture of CTGF expression matched the Masson's trichrome. No significant difference was observed in Ki-67 expression. Conclusions: The results of the current study suggest that the stimulation is so intense that it causes significant damage to adrenal cortical cells, resulting in their apoptosis. It seems, however, that the observed effects are at least partially reversible.


Assuntos
Cafeína/efeitos adversos , Bebidas Energéticas/efeitos adversos , Gotículas Lipídicas , Taurina/efeitos adversos , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Glomerulosa/metabolismo , Zona Glomerulosa/patologia , Animais , Apoptose , Caspase 3/biossíntese , Colágeno/biossíntese , Fator de Crescimento do Tecido Conjuntivo/biossíntese , Antígeno Ki-67/biossíntese , Masculino , Ratos , Ratos Wistar , Zona Fasciculada/citologia , Zona Glomerulosa/citologia
4.
Folia Morphol (Warsz) ; 77(4): 629-641, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29611160

RESUMO

BACKGROUND: Stress exposure exerts direct effects on the morphology and functionality of the adrenal cortex. In addition, ageing effects growth, differentiation, apoptosis and cellularity of the cortex. The missing data is the combined effect of stress and ageing on the adrenal cortex. The aim of this study was to demonstrate the structural changes in the adrenal cortex following the exposure to stress in the adult and aged albino rats. MATERIALS AND METHODS: Forty rats were divided into groups I and II (adult and senile). Each group was further subdivided into subgroups a and b (control and stressed). Light and electron microscopic studies were done. Area per cent of collagen fibres (Masson's trichrome-stained sections), number of proliferating cells (optical density immunoreactivity in the Ki67 stained sections) and thickness of the three adrenal zones were also measured. RESULTS: Lamellar separation of the capsule with subcapsular spindle cell hyperplasia and areas of ghost cells were observed in zona glomerulosa (ZG) and zona fasciculata (ZF) in group I-b. Separation and indentation of the capsule with its lamellar separation were observed in group II-a with the existence of multiple scattered degenerative foci in ZF and zona reticularis (ZR). Similar and aggressive was the architectural pattern of ZF in group II-b with the presence of areas of homogenous degeneration. The nuclei of ZG had marginated chromatin in group I-b and were pyknotic with deformed irregular outlines in group II-b. Multiple lysosomes and vacuolar degeneration mitochondria were also seen in group I-b. The nuclei of ZF were irregular with condensed marginated heterochromatin in group I-b, irregular with scattered chromatin in group II-a and indented with areas of chromatin destruction in group II-b. Mitochondria with disrupted cristae and cristolysis were also detected in group I-b. Numerous lipofuscin granules and dilated smooth endoplasmic reticulum were revealed in group II-b. The mean collagen fibre area per cent and the mean number of the proliferating cells in group II-b were significantly higher by 39% and 23%. The thickness of ZG decreased significantly by 20% in group I-b. Contrary, the thickness of both ZF and ZR increased significantly by 10% in group I-b. CONCLUSIONS: Histological alterations occurred in the adrenal cortex in response to stress, especially when coupled with the advance of age. This was accompanied by increase in the area per cent of collagen fibres and increase in the mean number of the proliferating cells in the adrenal cortex.


Assuntos
Envelhecimento/patologia , Estresse Psicológico , Zona Fasciculada , Zona Glomerulosa , Zona Reticular , Animais , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Glomerulosa/metabolismo , Zona Glomerulosa/patologia , Zona Reticular/metabolismo , Zona Reticular/patologia
5.
Endocrine ; 58(3): 503-512, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28405879

RESUMO

PURPOSE: Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined. THE AIMS OF OUR STUDY WERE: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11ß-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth. METHODS: Archival micro-dissected paraffin-embedded slides from tumor specimens were used for histological and molecular studies. Immunohistochemistry was performed using monoclonal anti-CYP11B1 and anti-CYP11B2 antibodies. Cellular composition was determined by examining for known features of zona fasciculata and zona glomerulosa, and immunoreactivity for CYP11B1 and CYP11B2 by McCarty H-score. Spot regions for mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, PRKACA, and CTNNB1 gene sequences were evaluated. RESULTS: Four APAs showed a predominant (≥50%) zona fasciculata-like cell pattern: one tumor had CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACA p.Leu206Arg mutation (that we have reported previously elsewhere), one had no CYP11B1 expression, CYP11B2 H-score = 40, and no mutations; the remaining two adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H-score (30 and 15, respectively), with the latter harboring a CTNNB1 p.Ser45Phe activating mutation. One of five aldosterone-producing adenomas had a predominant zona glomerulosa-like pattern, CYP11B1 H-score = 15, CYP11B2 H-score = 180, and no mutations. CONCLUSIONS: The majority of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion were composed mainly of zona fasciculata-like cells, while CYP11B1 and CYP11B2 immunostaining demonstrated clear heterogeneity. In a subset of cases, different somatic mutations may be involved in hormone excess and tumor formation.


Assuntos
Adenoma/metabolismo , Adenoma/patologia , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Aldosterona/metabolismo , Hidrocortisona/sangue , Adenoma/genética , Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Citocromo P-450 CYP11B2/sangue , Citocromo P-450 CYP11B2/genética , Feminino , Humanos , Hidrocortisona/metabolismo , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Esteroide 11-beta-Hidroxilase/sangue , Esteroide 11-beta-Hidroxilase/genética , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia
6.
J Clin Endocrinol Metab ; 102(6): 1792-1796, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28368480

RESUMO

Context: Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear. Case Description: A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas. Two zona fasciculata (ZF)-like aldosterone-producing adenomas (APAs) each harbored distinct known somatic KCNJ5 mutations (L168R and T158A). A zona glomerulosa-like APA harbored a known CACNA1D G403R somatic mutation, whereas a zona reticularis-like adenoma, which was grossly black in pigmentation with histologic characteristics more associated with cortisol-producing adenomas, expressed CYP11B2, CYP17, and DHEA-ST by immunohistochemistry (IHC) and harbored no known somatic mutations. The fifth adenoma was ZF-type, negative for CYP11B2 and CYP17 IHC, and harbored no known somatic mutations. Conclusions: This case highlights complex intertumor heterogeneity in histology, steroidogenesis, and somatic mutations in multiple adrenocortical adenomas arising in a single patient with PA. These findings suggest that the syndrome of PA can involve heterogeneous and multiclonal functional adrenal adenomas.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Hiperaldosteronismo/genética , Neoplasias Primárias Múltiplas/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Adenoma Adrenocortical/cirurgia , Canais de Cálcio Tipo L/genética , Citocromo P-450 CYP11B2/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Humanos , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Hiperaldosteronismo/cirurgia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Esteroide 17-alfa-Hidroxilase/metabolismo , Sulfotransferases/metabolismo , Zona Fasciculada/patologia , Zona Glomerulosa/patologia , Zona Reticular/patologia
7.
J Clin Endocrinol Metab ; 97(5): E819-29, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22442279

RESUMO

CONTEXT: Aldosterone-producing adenomas (APA) are heterogeneous. The recent finding of somatic KCNJ5 mutations suggests a genetic explanation. OBJECTIVES: The objectives of this study were the following: 1) to compare transcriptional profiles in APA and adjacent adrenal gland (AAG); 2) to test whether gene expression profile clusters with different cell histology; and 3) to measure the frequency of KCNJ5 mutations and determine the genotype-phenotype relationship. DESIGN/SETTING: The design of the study included laboratory analyses of 46 unselected APA. PATIENTS: The patients in this study had primary hyperaldosteronism with unilateral APA. INTERVENTIONS: The objectives of this study were the following: 1) Illumina beadchip analysis of RNA from eight paired APA-AAG; 2) a blinded review of cell histology for 46 APA; 3) laser capture microdissection of zona glomerulosa (ZG) and zona fasciculata (ZF) cells; and 4) sequencing of KCNJ5 in 46 APA. MAIN OUTCOME MEASURES: The main outcome measures of this study were the following: 1) a difference in gene expression profile and a correlation with histological markers of ZF; 2) a frequency of KCNJ5 mutations and phenotypic comparisons of wild type with mutant APA. RESULTS: The results of the study were the following: 1) a cluster analysis of microarray data separated APA from AAG. APA at opposite ends of the APA cluster had an approximately 800-fold difference in CYP17A1 mRNA expression, whereas histology showed 0% ZF-like cells in one vs. 100% in the other. A heat map ranking APA by CYP17A1 expression correctly predicted several genes (e.g. KCNK1, SLC24A3) to be enriched in laser capture microdissection samples of ZG; 2) known or novel mutations of KCNJ5 were found in 20 of 46 consecutive APA [43% (95% confidence interval [CI] (29, 58)%)]. The APA with KCNJ5 gene mutations were larger compared with tumors harboring the wild type, 1.63 [95% CI (1.37, 1.88)] vs. 1.14 [0.97, 1.30] cm (P = 0.0013), had predominantly ZF-like cells, and their CYP17A1 (log(2)-fold change) was higher than in wild type: -0.96 [95% CI (-0.07, -1.85)] vs. -2.54 [-1.61, -3.46], (P = 0.017). CONCLUSIONS: KCNJ5 mutations are common in APA, particularly those arising from ZF. The long-recognized heterogeneity among APA may have a genetic basis.


Assuntos
Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Aldosterona/biossíntese , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hiperaldosteronismo/genética , Zona Fasciculada/metabolismo , Zona Glomerulosa/metabolismo , Adenoma/metabolismo , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Genótipo , Humanos , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Zona Fasciculada/patologia , Zona Glomerulosa/patologia
8.
Alcohol Alcohol ; 46(5): 523-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21610084

RESUMO

AIMS: The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. METHODS: Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. RESULTS: Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. CONCLUSION: Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.


Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Óxido Nítrico/fisiologia , Córtex Suprarrenal/patologia , Córtex Suprarrenal/fisiologia , Hormônio Adrenocorticotrópico/biossíntese , Hormônio Adrenocorticotrópico/sangue , Animais , Corticosterona/biossíntese , Corticosterona/sangue , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Estro/fisiologia , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Radioimunoensaio , Ratos , Ratos Wistar , Fatores de Tempo , Zona Fasciculada/patologia
9.
Gen Physiol Biophys ; 24(3): 299-309, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16308425

RESUMO

The effect of chronic exposure to light of adult Wistar rats on growth and function of adrenal zona glomerulosa (ZG) and zona fasciculata (ZF) were examined. The females were exposed to continuous light of 600 lux for 95 days, starting on day 30 of age. The controls were kept under a 12:12 h light-dark cycle, at ambient temperature. The rats were sacrificed by decapitation and the left adrenal gland of each animal was dissected out and prepared for morphometric analyses. In animals exposed to chronic lighting, the absolute and relative volume of ZG were insignificantly increased by 5% (p>0.05) compared to controls. The volume of ZG cells and their nuclei were insignificantly changed by 1% (p>0.05) in comparison with corresponding controls. The absolute and relative volume of ZF were significantly increased (by 14 and 9%, respectively; p<0.05), as compared to controls. The volume of ZF cells and their nuclei were significantly increased (by 12 and 9%, respectively; p<0.05). Serum concentration of corticosterone was also significantly (p<0.05) increased by 13% in light-exposed group in comparison with control rats. These findings suggest that continuous exposure of female rats to constant light increased growth and secretory activity of ZF cells.


Assuntos
Glândulas Suprarrenais/efeitos da radiação , Sistema Endócrino/efeitos da radiação , Zona Fasciculada/patologia , Zona Fasciculada/efeitos da radiação , Zona Glomerulosa/patologia , Zona Glomerulosa/efeitos da radiação , Córtex Suprarrenal , Animais , Peso Corporal , Corticosterona/uso terapêutico , Feminino , Luz , Radioimunoensaio , Ratos , Ratos Wistar , Temperatura Ambiente , Fatores de Tempo
10.
J Coll Physicians Surg Pak ; 15(7): 383-6, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16197863

RESUMO

OBJECTIVE: To investigate the effects of carbimazole-induced hypothyroidism, and simultaneous administration of thyroxine (thyroid hormone analogue) on the adrenal glands of 10 days' prenatally treated albino rats. DESIGN: A comparative study. PLACE AND DURATION OF STUDY: Department of Anatomy, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from 15th July 2001 to 31st August 2001. PATIENTS AND METHODS: Ten days old albino rats of either gender, which were delivered by their respective mothers which were originally obtained from Charles River Breeding Laboratories, Brooklyn, Massachusetts, USA, and were cross bred, housed and maintained on the balanced diet in the Animal House of BMSI, JPMC, Karachi. Eighteen prenatally treated albino rats of 10 days old were used in the experiment and divided into three groups: X, Y and Z, comprising 06 animals in each group, i.e. from carbimazole treated mothers (X), carbimazole plus thyroxine treated mothers (Y), and controlled mothers (Z). At the end of 10th postnatal day all the animals were sacrificed, their adrenal glands were removed, fixed, sectioned, and stained with H&E. The adrenal histology with relation to its width of cortex, zones and number of cells in different zones of cortex were studied. RESULTS: Carbimazole-induced hypothyroidism causes the adrenal atrophy in the adrenals of 10 days' prenatally treated albino rats by decreasing the total width of cortex and its zones especially zona fasciculata. CONCLUSION: Carbimazole-induced hypothyroidism by carbimazole causes the shrinkage of adrenal cortex in 10 days prenatally treated albino rats.


Assuntos
Glândulas Suprarrenais/patologia , Hipotireoidismo/patologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Antitireóideos/efeitos adversos , Carbimazol/efeitos adversos , Hipotireoidismo/induzido quimicamente , Masculino , Ratos , Tiroxina/farmacologia , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/patologia
11.
J Exp Biol ; 207(Pt 24): 4225-30, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15531643

RESUMO

The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.


Assuntos
Glândulas Suprarrenais/fisiologia , Temperatura Alta , Ratos/fisiologia , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Animais , Corticosterona/sangue , Técnicas Histológicas , Masculino , Tamanho do Órgão , Ratos Wistar , Zona Fasciculada/patologia , Zona Fasciculada/fisiologia
12.
Endocrine ; 24(2): 167-75, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15347844

RESUMO

Neonatal treatment of rats with monosodium L-glutamate, which destroys hypothalamic arcuate nucleus neuronal bodies, induces several metabolic abnormalities; as a result, rats develop a phenotype of pseudoobesity. This study was designed to explore, in the monosodium L-glutamate-treated female rat, the influence of chronic hyperleptinemia on adrenal cortex functionality. For this purpose, we evaluated in control and hypothalamic-damaged rats: (a) in vivo and in vitro adrenocortical function, (b) adrenal leptin receptor immunodistribution and mRNA expression, and (c) whether the inhibitory effect of leptin on adrenal function remains. Our results indicate that, compared to normal counterparts, pseudoobese animals displayed (1) hyperadiposity, despite being hypophagic and of lower body weight, (2) in vivo and in vitro enhanced adrenocortical response to ACTH stimulation, (3) an in vitro adrenal fasciculata-reticularis cell hyper-sensitivity to ACTH stimulus, (4) hyperplasia of their adrenal zona fasciculata cells, and (5) adrenal fasciculata-reticularis cell refractoriness to the inhibitory effect of leptin on ACTH-stimulated glucocorticoid production due, at least in part, to decreased adrenal leptin receptor expression. These data further support that increased hypothalamo-pituitary-adrenal axis function, in the adult neurotoxin-lesioned female rat, is mainly dependent on the development of both hyperplasia of adrenal zona fasciculata and adrenal gland refractoriness to leptin inhibitory effect. Our study supports that adrenal leptin resistance could be responsible, at least in part, for enhanced glucocorticoid circulating levels in this phenotype of obesity.


Assuntos
Córtex Suprarrenal/fisiopatologia , Leptina/sangue , Córtex Suprarrenal/química , Córtex Suprarrenal/efeitos dos fármacos , Glândulas Suprarrenais/química , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/fisiopatologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Animais Recém-Nascidos , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Glucocorticoides/biossíntese , Glucocorticoides/sangue , Hiperplasia , Doenças Hipotalâmicas/induzido quimicamente , Doenças Hipotalâmicas/fisiopatologia , Leptina/farmacologia , Obesidade/etiologia , RNA Mensageiro/análise , Ratos , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/genética , Receptores para Leptina , Glutamato de Sódio/administração & dosagem , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/patologia , Zona Fasciculada/fisiopatologia
13.
Eur J Clin Invest ; 33(9): 794-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12925039

RESUMO

BACKGROUND: Recombinant adenoviruses are widely used in gene therapy clinical trials. A particular tropism for the adrenal glands has been reported but the precise cellular base for this tropism has not been determined. MATERIALS AND METHODS: Recombinant adenoviruses were injected intravenously into Balb/c nu/nu or C57BL/6 mice. Seventy-two hours later, the animals were sacrificed and the adrenal glands and livers collected. The glands were sectioned and analyzed using immunohistochemical methods to detect adenoviral epitopes and transgene expression. Total RNA were extracted from the liver and adrenal glands of some animals and subjected to real-time RT-PCR. RESULTS: The only cell type infected in the adrenal glands of Balb/c nu/nu or C57BL/6 mice is the adrenocortical cells in the zona fasciculata. Quantitatively, the relative level of gene expression in the adrenal gland is comparable but lower than that measured in the liver. CONCLUSIONS: Systemic injection of recombinant adenovirus could be used as a procedure to restore adrenal steroidogenesis in clinical gene therapy protocols. In addition, our study suggest that adrenal dysfunction should be considered when criteria are established to assess the safety of gene therapy formulations administered systemically.


Assuntos
Infecções por Adenoviridae/genética , Glândulas Suprarrenais/microbiologia , Tropismo/genética , Adenoviridae/genética , Adenoviridae/crescimento & desenvolvimento , Infecções por Adenoviridae/patologia , Glândulas Suprarrenais/patologia , Animais , DNA Recombinante/genética , DNA Viral/genética , Feminino , Expressão Gênica , Imuno-Histoquímica/métodos , Fígado/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Zona Fasciculada/microbiologia , Zona Fasciculada/patologia
14.
Histochem Cell Biol ; 119(5): 415-22, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12783238

RESUMO

Feline spongiform encephalopathy (FSE), affecting domestic and captive feline species, is a prion disease considered to be related to bovine spongiform encephalopathy. Here we report an immunohistological analysis of the first FSE-affected cheetah born in France. The duration of clinical signs, of which ataxia was the main one, was about 8 weeks. The distribution of abnormal prion protein (PrP(sc)) was studied by immunohistochemistry within 27 different tissues. Different antibodies were used to visualise abnormal PrP deposits in situ. PrP(sc )accumulation was detected in the central nervous system (cerebral cortex, cerebellum, brain stem, spinal cord, retina), in peripheral nerves and in lymphoid organs. PrP(sc) deposits were not observed within the enteric nervous system nor in several other organs, such as pancreas, ovary, liver and muscle. More interestingly, unusual PrP(sc )deposits were observed within the zona fasciculata/reticularis of the adrenal gland and within some glomeruli of the kidney raising the question of possible PrP(sc) excretion. The sympathetic innervation of these two organs was visualised and compared to the distribution of PrP(sc) deposits. Our results suggest the possibility that the infectious agent is spread by both haematogenous and nervous pathways.


Assuntos
Acinonyx , Glândulas Suprarrenais/patologia , Animais de Zoológico , Glomérulos Renais/patologia , Proteínas PrPSc/metabolismo , Doenças Priônicas/veterinária , Glândulas Suprarrenais/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Feminino , França , Técnicas Imunoenzimáticas/veterinária , Glomérulos Renais/metabolismo , Linfonodos/metabolismo , Linfonodos/patologia , Sistema Nervoso Periférico/metabolismo , Sistema Nervoso Periférico/patologia , Doenças Priônicas/metabolismo , Doenças Priônicas/patologia , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Reticular/metabolismo , Zona Reticular/patologia
15.
Bull Exp Biol Med ; 133(5): 506-9, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12420075

RESUMO

Directional left-sided asymmetry of the adrenals was typical of black and silver foxes, American minks, and gray rats selected by their behavior. In domesticated, but to a greater extent, in aggressive animals, the weight of the left adrenal and the width of its medulla and cortex markedly surpassed the corresponding parameters of the right adrenal. In aggressive animals enlargement of the left adrenal cortex was associated with widening of the zona reticularis, while in domesticated animals with enlargement of the zona fasciculata.


Assuntos
Córtex Suprarrenal/fisiologia , Lateralidade Funcional , Córtex Suprarrenal/patologia , Animais , Feminino , Raposas , Masculino , Vison , Tamanho do Órgão , Ratos , Fatores de Tempo , Zona Fasciculada/patologia , Zona Reticular/patologia
16.
Morfologiia ; 121(1): 27-30, 2002.
Artigo em Russo | MEDLINE | ID: mdl-12108096

RESUMO

Rat adrenals were studied using histological and histochemical methods during prolonged intoxication with pesticide magnesium chlorate which was administered in a dose equal to 1/100 of LD50 (41 mg/kg of body weight). Animals that received distilled water and were kept in similar conditions were used as control. It was demonstrated that intoxication of rats for 3-7 days results in increased secretory activity of all the zones of adrenal cortex. Later (after 14-90 days) the zonal response to pesticide administration was variable. Magnesium chlorate treatment results in the disturbances of hormonal synthesis in adrenocorticocytes. Compensatory-adaptive capacities of zona fasciculata were found to be greater than those in zona glomerulosa and zona reticularis.


Assuntos
Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/patologia , Cloratos/toxicidade , Compostos de Magnésio/toxicidade , Administração Oral , Córtex Suprarrenal/metabolismo , Animais , Cloratos/administração & dosagem , Glicogênio/metabolismo , Imuno-Histoquímica , Dose Letal Mediana , Metabolismo dos Lipídeos , Compostos de Magnésio/administração & dosagem , Masculino , RNA/metabolismo , Ratos , Fatores de Tempo , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Reticular/efeitos dos fármacos , Zona Reticular/metabolismo , Zona Reticular/patologia
17.
Morfologiia ; 122(5): 66-9, 2002.
Artigo em Russo | MEDLINE | ID: mdl-12530311

RESUMO

The comparative investigation of the adrenal structure in two groups of rats of Inherited Stress-Induced Arterial Hypertension (ISIAH) strain was conducted. The animals of the first group were nursed by normotensive Wistar rats, while those of the second (control) group were reared by their own mothers. The volume of the adrenal medulla in rats of the first group was found to exceed that in the second group. In the adrenal zona glomerulosa and zona fasciculata of 3-week-old rats of the first group parenchymal-stromal ratio and the average volume of adrenocorticocytes were lower than those in the animals of the second group. This was accompanied by a decrease in mitochondrial volume density and accumulation of lipid droplets in the cytoplasm, indicating a reduction of hormone-producing activity of endocrinocytes in the animals the first group as compared to controls. By 6 month of age, arterial pressure and quantitative parameters of adrenal medulla and cortex in the animals the first group were..... as compared to those in the second group. It is suggested that the nursing of ISIAH rat pups by normotensive Wistar dams had modulating effect on the adrenal structure and therefore on arterial hypertension development.


Assuntos
Córtex Suprarrenal/ultraestrutura , Hipertensão/patologia , Estresse Fisiológico/complicações , Córtex Suprarrenal/patologia , Animais , Animais Lactentes , Pressão Sanguínea , Feminino , Hipertensão/etiologia , Hipertensão/genética , Hipertensão/fisiopatologia , Lactação/fisiologia , Microscopia Eletrônica , Tamanho do Órgão , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Zona Fasciculada/patologia , Zona Fasciculada/ultraestrutura , Zona Glomerulosa/patologia , Zona Glomerulosa/ultraestrutura
18.
Biomed Sci Instrum ; 37: 155-60, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11347380

RESUMO

The role of reproductive and adrenal steroid hormones on the structural and functional capacity of adrenal tissue has not been well investigated. The objective of this investigation was to morphometrically evaluate the effect of testosterone (T), dihydrotestosterone (DHT), and androstenedione (AED) given in a sustained manner, by tricalcium phosphate lysine (TCPL) ceramic capsules, on the adrenals of adult male rats. Sixteen adult male rats were randomly divided into four equal groups. Groups II, III, and I were implanted with TCPL capsules loaded with AED, T, and DHT, respectively. Group IV animals were not implanted, and thus served as the control group. At the end of ninety days post-implantation, the animals were euthanized using standard aseptic surgical techniques. The adrenal glands were harvested and stored in 10% formalin. The tissues were processed, embedded, sectioned and stained with H & E using standard laboratory procedure. Random sections of control and experimental tissues were utilized for morphometric analysis by using Image Pro digital analysis techniques. Data collected were analyzed by means of ANOVA (p < 0.05). Results of this study revealed. (1) There was an increase in the total areas of T treated animals in comparison to the control and other experimental groups, (2) the total lengths of each hormonally treated tissue showed an increase in size of DHT treated tissue verses control, but differences of T and AED compared with control remained insignificant, (3) upon analysis of the zona glomerulosa (Z1) and zona fasciculata (Z2) the data demonstrated a significant increase in animals treated with DHT and AED in comparison to control and T treated animals, (4) finally, statistical analysis performed on measurements of the zona reticularies (Z3) indicated notable increases only in the AED exposed animals. The changes in size of the various tissues may be warranted due to reactions of the steroid hormones with different surface receptors in different layers. However, further investigations are needed, especially longer duration of treatment, to fully hypothesize the exact mechanisms of these hormones on the adrenal glands.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Androgênios/administração & dosagem , Fosfatos de Cálcio , Sistemas de Liberação de Medicamentos , Lisina , Fosfatos , Glândulas Suprarrenais/patologia , Androgênios/farmacologia , Androstenodiona/administração & dosagem , Animais , Cerâmica , Di-Hidrotestosterona/administração & dosagem , Implantes de Medicamento , Masculino , Ratos , Ratos Sprague-Dawley , Testosterona/administração & dosagem , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/patologia , Zona Glomerulosa/efeitos dos fármacos , Zona Glomerulosa/patologia , Zona Reticular/efeitos dos fármacos , Zona Reticular/patologia
19.
Toxicol Sci ; 53(1): 135-44, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10653531

RESUMO

Chlorpyrifos (CPF) was administered daily in the feed to evaluate toxicity and oncogenicity potential in male and female Fischer 344 rats, according to U.S. EPA guidelines. Doses for the 2-year study were based on findings in a 13-week feeding study in which lower body weights, urinary perineal staining, adrenal cortical vacuolization, and inhibition (slightly more than 60%) of brain cholinesterase (ChE) occurred at 15 mg/kg/day. The high dose in the subsequent 2-year study was 10 mg/kg/day, with lower doses of 0, 0.05, 0.1, or 1.0 mg/kg/day chosen to define dose-response patterns. Rats given 10 mg/kg/day for 2 years were healthy and there was no evidence of premature deaths. Mild toxicity occurred only in rats given 10 mg/kg/day and consisted of perineal urine soiling in females and a 6-8% body-weight decrease in males. Males given 10 mg/kg/day also had increased adrenal weights and vacuolation of the adrenal zona fasciculata. ChE was considered a measure of exposure. Plasma, RBC, and brain ChE activities were inhibited in rats given 10 mg/kg/day, and the plasma and RBC ChE activities were inhibited in rats given 1.0 mg/kg/day. Chronic exposure to 0.1 mg/kg/day was considered a threshold exposure level for inhibition of plasma ChE. Rats given 10 mg/kg/day, considered a maximum-tolerated dose, had approximately 60% chronic inhibition of brain ChE. This group had similar numbers and types of neoplasms as control rats. Consequently, CPF was not carcinogenic at dose levels up to 10 mg/kg/day.


Assuntos
Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Colinesterases/metabolismo , Dieta , Feminino , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/patologia
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