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1.
Eur J Endocrinol ; 182(3): 265-273, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32038030

RESUMO

Objectives: We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). Design: Multicenter retrospective study by Japan PA study. Method: We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Results: Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Conclusions: Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.


Assuntos
Glândulas Suprarrenais/metabolismo , Cosintropina/farmacologia , Hiperaldosteronismo/cirurgia , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/efeitos dos fármacos , Adrenalectomia , Adenoma Adrenocortical/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
2.
Biosci Biotechnol Biochem ; 84(3): 606-612, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31746674

RESUMO

Royal jelly (RJ) is used as a dietary supplement for human health promotion. Recently, a clinical trial has reported that RJ improved mental health. The present study was conducted to experimentally support the clinical effect of RJ on mental health and to further elucidate the mechanisms of action of RJ. RJ and an ethanol extract of RJ, which contains fatty acids but not proteins, inhibited an unpredictable chronic mild stress (UCMS)-induced increase in immobility time, a depression-like behavior, in the tail suspension test. DNA microarray analysis of the adrenal grand revealed that the expression of genes involved in cholesterol metabolism was up-regulated in response to UCMS exposure and that RJ suppressed expression of genes related to cholesterol synthesis and transport. These results suggested that RJ improves stress-induced depression-like behavior by regulating adrenal steroidogenesis and that fatty acids contained in RJ partly contribute to the antidepressant effect of RJ.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Corticosterona/biossíntese , Depressão/prevenção & controle , Ácidos Graxos/farmacologia , Estresse Fisiológico , Glândulas Suprarrenais/metabolismo , Animais , Peso Corporal , Doença Crônica , Corticosterona/sangue , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
3.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(12): 158533, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31676438

RESUMO

Circadian clocks coordinate physiological and behavioral rhythms that allow the organism to anticipate and adapt to daily changes in environment. The clock-driven cellular oscillations are highly tissue specific to efficiently fine-tune local signaling, manage energy use and segregate incompatible processes. In most peripheral tissues, food acts as the main cue that entrains the oscillations to external time. Food intake and energy balance are under control of endocannabinoid (EC) signaling. Despite this obvious link between the circadian and EC systems, evidence for their interaction started to emerge only recently. We used targeted lipidomics to analyze circadian variations in EC tone in rat plasma, liver and adrenal tissue. The results provide the evidence that ECs, monoacylglycerols, N-acylethanolamines and their precursors oscillate with a tissue-specific circadian phase in plasma and liver. We then identified a set of rhythmically expressed genes likely responsible for the variations in EC tissue tone. In contrast to the liver, EC levels did not oscillate in the adrenal glands. Instead, we revealed that local EC receptor genes are under circadian regulation. To explore the impact of metabolic signals on expression of these genes, we used daytime-restricted feeding schedule. We subsequently showed that daytime feeding strongly suppressed liver-expressed fatty acid binding protein 5 (Fabp5) and adrenal-expressed non-canonical endocannabinoid receptors Gpr55 and Trpv1, whereas it upregulated liver-expressed Trpv1 and glycerophosphodiester phosphodiesterase 1 (Gde1). Our results reveal tissue-specific mechanisms involved in interaction between endocannabinoid signaling, circadian system and metabolism.


Assuntos
Glândulas Suprarrenais/metabolismo , Ritmo Circadiano , Endocanabinoides/metabolismo , Fígado/metabolismo , Animais , Regulação do Apetite , Relógios Circadianos , Endocanabinoides/sangue , Metabolismo Energético , Comportamento Alimentar , Masculino , Fotoperíodo , Ratos , Ratos Wistar
4.
Bioelectromagnetics ; 40(8): 578-587, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31642089

RESUMO

A sub-acute electromagnetic field (EMF) biological effect study was carried out on rats exposed in the Transverse ElectroMagnetic exposure chamber at 171 MHz Continuous Wave (CW). The experiments involved three exposure levels (15, 25, and 35 V/m) for 15 days with triplicate parallel sham-exposed controls in each series. All exposure conditions were simulated for the evaluation of the electromagnetic energy distribution and specific absorption rate (SAR) in the rat phantoms. Studies have shown a biphasic biological response depending on time and absorbed electromagnetic energy. Under low SAR, approximately 0.006 W/kg, EMF exposure leads to the stimulation of adrenal gland activity. This process is accompanied by an initial increase of daily excretion of corticosterone and Na+ , which is seen as a higher Na+ /K+ ratio, followed by a decrease of these parameters over time. It is possible that EMF exposure causes a stress response in animals, which is seen as an increased adrenal activity. Bioelectromagnetics. 2019;40:578-587. © 2019 Bioelectromagnetics Society.


Assuntos
Glândulas Suprarrenais/metabolismo , Campos Eletromagnéticos/efeitos adversos , Glucocorticoides/metabolismo , Mineralocorticoides/metabolismo , Animais , Corticosterona/metabolismo , Masculino , Potássio/metabolismo , Ratos , Ratos Wistar , Sódio/metabolismo
5.
Endocrinology ; 160(11): 2517-2528, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504388

RESUMO

ACSL4 is a member of the ACSL family that catalyzes the conversion of long-chain fatty acids to acyl-coenzyme As, which are essential for fatty-acid incorporation and utilization in diverse metabolic pathways, including cholesteryl ester synthesis. Steroidogenic tissues such as the adrenal gland are particularly enriched in cholesteryl esters of long-chain polyunsaturated fatty acids, which constitute an important pool supplying cholesterol for steroid synthesis. The current studies addressed whether ACSL4 is required for normal steroidogenesis. CYP11A1 promoter‒mediated Cre was used to generate steroid tissue‒specific ACSL4 knockout (KO) mice. Results demonstrated that ACSL4 plays an important role in adrenal cholesteryl ester formation, as well as in determining the fatty acyl composition of adrenal cholesteryl esters, with ACSL4 deficiency leading to reductions in cholesteryl ester storage and alterations in cholesteryl ester composition. Statistically significant reductions in corticosterone and testosterone production, but not progesterone production, were observed in vivo, and these deficits were accentuated in ex vivo and in vitro studies of isolated steroid tissues and cells from ACSL4-deficient mice. However, these effects on steroid production appear to be due to reductions in cholesteryl ester stores rather than disturbances in signaling pathways. We conclude that ACSL4 is dispensable for normal steroidogenesis.


Assuntos
Corticosteroides/biossíntese , Glândulas Suprarrenais/metabolismo , Coenzima A Ligases/metabolismo , Hormônios Esteroides Gonadais/biossíntese , Animais , Coenzima A Ligases/genética , Feminino , Masculino , Camundongos Knockout
6.
J Toxicol Sci ; 44(9): 575-584, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474739

RESUMO

The adrenal gland is the most common toxicological target of drugs within the endocrine system, and inhibition of adrenal steroidogenesis can be fatal in humans. However, methods to evaluate the adrenal toxicity are limited. The aim of the present study was to verify the usefulness of simultaneous measurement of blood levels of multiple adrenal steroids, including precursors, as a method to evaluate drug effects on adrenal steroidogenesis in cynomolgus monkeys. With this aim, physiological and drug-induced changes in blood levels of adrenal steroids, including cortisol, aldosterone, androgen, and their precursors were examined. First, for physiological changes, intraday and interday changes in blood steroid levels were examined in male and female cynomolgus monkeys. The animals showed circadian changes in steroid levels that are similar to those in humans, while interday changes were relatively small in males. Next, using males, changes in blood steroid levels induced by ketoconazole and metyrapone were examined, which suppress adrenal steroidogenesis via inhibition of CYP enzymes. Consistent with rats and humans, both ketoconazole and metyrapone increased the deoxycorticosterone and deoxycortisol levels, probably via CYP11B1 inhibition, and the increase was observed earlier and with greater dynamic range than the changes in cortisol level. Changes in other steroid levels reflecting the drug mechanisms were also observed. In conclusion, this study showed that in cynomolgus monkeys, simultaneous measurement of blood levels of adrenal steroids, including precursors, can be a valuable method to sensitively evaluate drug effects on adrenal steroidogenesis and to investigate the underlying mechanisms.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Aldosterona/sangue , Aldosterona/metabolismo , Androgênios/sangue , Androgênios/metabolismo , Cromatografia Líquida/métodos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Cetoconazol/toxicidade , Metirapona/toxicidade , Espectrometria de Massas em Tandem/métodos , Animais , Ritmo Circadiano , Desoxicorticosterona/metabolismo , Feminino , Humanos , Macaca fascicularis , Masculino , Esteroide 11-beta-Hidroxilase/antagonistas & inibidores
7.
J Toxicol Sci ; 44(9): 601-610, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474741

RESUMO

To verify simultaneous measurement of blood levels of adrenal steroids as a tool to evaluate drug effects on adrenal steroidogenesis, dose- and time-dependent changes in blood levels of corticosterone and its precursors (pregnenolone, progesterone and deoxycorticosterone), as well as their relationship with the pathological changes in the adrenal gland, were examined in rats dosed with ketoconazole (KET). Also examined were whether effects on adrenal steroidogenesis that were not obvious in the blood steroid levels after sole administration of KET could be revealed by post-administration of ACTH, and the correlation between the blood and adrenal steroid levels. Male rats were dosed with 15, 50, or 150 mg/kg of KET for 1 or 7 days with or without ACTH, and the blood and adrenal concentrations of the steroids were measured. KET increased the blood deoxycorticosterone level even at a dose level and time point at which histopathological changes were not obvious. KET-induced changes in blood levels of other steroids were revealed by ACTH, and the blood and adrenal levels were generally correlated especially after ACTH post-administration. Thus, blood levels of adrenal steroids, including precursors, can be a sensitive and early marker of drug effects on the adrenal steroidogenesis that reflect adrenal levels of steroids. The usefulness of the multiple steroid measurement as a method for mechanism investigation of drug effects on the adrenal gland can be further enhanced by ACTH.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Desoxicorticosterona/sangue , Desoxicorticosterona/metabolismo , Cetoconazol/toxicidade , Pregnenolona/sangue , Pregnenolona/metabolismo , Progesterona/sangue , Progesterona/metabolismo , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Cromatografia Líquida , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Fatores de Tempo
8.
Eur J Endocrinol ; 181(4): C13-C15, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505455

RESUMO

A study has examined the rates of adrenal crises in patients treated with pituitary or adrenal surgery. Rates were substantial (approximately 9 per 100 patient years), perhaps representing suppression of corticotrope ACTH secretion and deprivation of normal corticotrope number postoperatively. Hormone withdrawal syndrome may have contributed to the rates of apparent adrenal crises given the definition used. Higher rates were seen in patients given relatively high dose glucocorticoids postoperatively in one of the two centres where patients were treated - perhaps some of the patients in the high dose centre had longer periods of corticotrope suppression from exogenous glucocorticoids, increasing the risk period for adrenal crises. The question of optimal glucocorticoid dose and weaning rate after cure of Cushing's syndrome remains a balance between weaning at a rate sufficiently rapid to allow resumption of normal corticotrope function thereby preventing adrenal crises and providing sufficient glucocorticoid support to avoid hormone withdrawal syndrome or even precipitating an adrenal crisis, in the vulnerable 4-6 month period after successful surgery. There is likely to be considerable inter-individual variability in optimum glucocorticoid dose and weaning rate so that close clinical and biochemical monitoring is currently a practical approach.


Assuntos
Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/terapia , Glândulas Suprarrenais/efeitos dos fármacos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Estudos Multicêntricos como Assunto/métodos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Resultado do Tratamento
9.
Pediatr Hematol Oncol ; 36(7): 422-431, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429623

RESUMO

Background: Children with acute lymphocytic leukemia (ALL) are enrolled in advanced treatment protocols involving high doses of glucocorticoids (GCs). Current protocols do not advocate tapering of GCs doses postinduction phase. Prolonged administration of supra-physiologic doses of GCs can induce transient suppression of the hypothalamic pituitary adrenal axis (HPA). Timely recognition of adrenal insufficiency is important in order to ensure that children at risk receive the necessary treatment and follow-up including stress coverage during illness and surgical procedures. Methods: 21 newly diagnosed patients with ALL aged 3-10 years old were prospectively enrolled in the study over a 2-year period. All enrolled patients received high doses of GCs as part of a chemotherapy treatment protocol. The HPA axis was assessed prior to the induction phase of chemotherapy and 1-2 weeks after un-tapered discontinuation of GCs. Results: All children had normal HPA axis at baseline. Postinduction 1 mcg ACTH stimulation test result was normal (cortisol > 500 nmol/L) in 75% of children and partially responsive in 25% (cortisol 300-500 nmol/L). None of the participants demonstrated clinically significant adrenal insufficiency following abrupt cessation of GCs. Conclusion: All children in our cohort had either normal or subnormal cortisol response during a low dose ACTH stimulation test 1 to 2 weeks following abrupt discontinuation of GCs, suggesting that any inhibition of the HPA axis is of short duration. We suggest that future studies investigate the timing of adrenal function recovery following GC discontinuation as well as whether tapering of the GC should be recommended.


Assuntos
Glândulas Suprarrenais/metabolismo , Glucocorticoides/administração & dosagem , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Pré-Escolar , Feminino , Glucocorticoides/efeitos adversos , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Prospectivos
10.
Hypertension ; 74(4): 809-816, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31446799

RESUMO

Aldosterone-producing adenomas with somatic mutations in the KCNJ5 G-protein-coupled inwardly rectifying potassium channel are a cause of primary aldosteronism. These mutations drive aldosterone excess, but their role in cell growth is undefined. Our objective was to determine the role of KCNJ5 mutations in adrenal cell proliferation and apoptosis. The Ki67 proliferative index was positively correlated with adenoma diameter in aldosterone-producing adenomas with a KCNJ5 mutation (r=0.435, P=0.007), a negative correlation was noted in adenomas with no mutation detected (r=-0.548, P=0.023). Human adrenocortical cell lines were established with stable expression of cumate-inducible wild-type or mutated KCNJ5. Increased cell proliferation was induced by low-level induction of KCNJ5-T158A expression compared with control cells (P=0.009), but increased induction ablated this difference. KCNJ5-G151R displayed no apparent proliferative effect, but KCNJ5-G151E and L168R mutations each resulted in decreased cell proliferation (difference P<0.0001 from control cells, both comparisons). Under conditions tested, T158A had no effect on apoptosis, but apoptosis increased with expression of G151R (P<0.0001), G151E (P=0.008), and L168R (P<0.0001). We generated a specific KCNJ5 monoclonal antibody which was used in immunohistochemistry to demonstrate strong KCNJ5 expression in adenomas without a KCNJ5 mutation and in the zona glomerulosa adjacent to adenomas irrespective of genotype as well as in aldosterone-producing cell clusters. Double immunofluorescence staining for KCNJ5 and CYP11B2 (aldosterone synthase) showed markedly decreased KCNJ5 immunostaining in CYP11B2-positive cells compared with CYP11B2-negative cells in aldosterone-producing adenomas with a KCNJ5 mutation. Together, these findings support the concept that cell growth effects of KCNJ5 mutations are determined by the expression level of the mutated channel.


Assuntos
Glândulas Suprarrenais/metabolismo , Proliferação de Células/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hiperaldosteronismo/genética , Glândulas Suprarrenais/patologia , Adulto , Idoso , Apoptose/fisiologia , Linhagem Celular , Feminino , Humanos , Hiperaldosteronismo/patologia , Masculino , Pessoa de Meia-Idade , Mutação
11.
Endocrinology ; 160(9): 2180-2188, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271415

RESUMO

Castration-resistant prostate cancer (PCa) almost invariably occurs after androgen deprivation therapy for metastatic disease and is driven in part by androgen synthesis within the tumor. 3ß-hydroxysteroid dehydrogenase isoenzyme-1 catalyzes the conversion of adrenal precursor steroids into potent androgens essential for PCa progression. A common 1245 A→C missense-encoding single nucleotide polymorphism in HSD3B1 (rs1047303), the gene that encodes this enzyme, leads to a more stable protein that is resistant to degradation and thus increased production of potent androgens from adrenal precursors, facilitating castration-resistant PCa development. Consistent with this mechanism, this adrenal-permissive HSD3B1(1245C) genotype is associated with inferior outcomes after androgen deprivation therapy for advanced PCa, and increased sensitivity to pharmacologic blockade of adrenal precursors in metastatic disease. Herein, we review current knowledge of the mechanisms conferred by HSD3B1 genotype to alter androgen physiology and accelerate development of castration-resistant disease and its associations with clinical PCa outcomes. In light of its effect on steroid physiology, we also discuss its potential associations with non-PCa phenotypes.


Assuntos
Glândulas Suprarrenais/metabolismo , Complexos Multienzimáticos/genética , Progesterona Redutase/genética , Neoplasias de Próstata Resistentes à Castração/genética , Esteroide Isomerases/genética , Androgênios/biossíntese , Desidroepiandrosterona/administração & dosagem , Suplementos Nutricionais , Genótipo , Humanos , Masculino , Complexos Multienzimáticos/fisiologia , Fenótipo , Progesterona Redutase/fisiologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/terapia , Esteroide Isomerases/fisiologia
12.
J Steroid Biochem Mol Biol ; 194: 105438, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31362063

RESUMO

The metabolism of drugs in mammals is attributed mainly to the liver and its cytochromes P450 localized in the endoplasmic reticulum. Here, we demonstrate for the first time in humans that there is no strict subdivision between P450 s involved in exogenous and endogenous metabolism. We determined the widely used mineralocorticoid receptor antagonist spironolactone, its active metabolite canrenone and their metabolites in the adrenal venous blood of treated patients with gas chromatography-mass spectrometry. 11- and 18-hydroxylated metabolites of canrenone were found in the efferent right and left adrenal veins, indicating that they were produced by the adrenal mitochondrial cytochromes P450 CYP11B1 and CYP11B2. Thus, the adrenal has to be considered as a new organ for drug metabolism. In future, application of drugs may need further investigations concerning side effects due to interactions with adrenal enzymes.


Assuntos
Glândulas Suprarrenais/metabolismo , Canrenona/sangue , Antagonistas de Receptores de Mineralocorticoides/farmacocinética , Espironolactona/farmacocinética , Idoso , Citocromo P-450 CYP11B2/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/sangue , Espironolactona/sangue , Esteroide 11-beta-Hidroxilase/metabolismo
13.
J Steroid Biochem Mol Biol ; 193: 105434, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31351131

RESUMO

Intracellular calcium (Ca) levels play pivotal roles in aldosterone biosynthesis. Several somatic mutations of ion channels associated with aldosterone over-production were reported to result in over-inflow of Ca ion. Recently, the main regulators of extracellular Ca including VDR, CaSR and PTH1R were also reported to regulate steroidogenesis including aldosterone production. Therefore, not only intracellular but also extracellular Ca levels could regulate aldosterone biosynthesis. In addition, primary aldosteronism (PA) is clinically associated with not only more frequent cardiovascular events but also secondary metabolic disorders including abnormal calcium metabolism, osteoporosis and others. However, the details of Ca metabolic abnormalities associated with, including the potential correlation between those abnormalities and aldosterone overproduction, have remained virtually unknown. Therefore, in this study, we first immunolocalized Ca metabolism-related receptors (CaSR, VDR and PTH1R) in normal adrenal glands (NAs), aldosterone-producing adenomas (APAs) and cortisol-producing adenoma (CPA). We then compared the findings with clinicopathological parameters of these patients and the patterns of KCNJ5 somatic mutation of the tumors among APA patients. In vitro study was also performed to further explore the potential effects of extracellular Ca, PTH, Vitamin D and ionophore on aldosterone production. Ca metabolism-related receptors were predominantly localized in aldosterone-producing cells (ZG and APA) in both immunohistochemistry and qRT-PCR analysis. CYP11B2 mRNA was significantly increased by CaCl2 treatment and further by adding ionophore. All the key enzymes related to aldosterone and cortisol biosynthesis including CYP11B2, CYP17A1 and CYP11B1 were upregulated by PTH treatment in this model and PTH could serve as a co-stimulator of ANG II to increase CYP11B2 expression. VDR mRNA levels were positively correlated with those of CYP11B2, CYP17A1 and CYP11B1 in APA tumor tissues and significantly higher in KCNJ5 mutated APAs than wild type. CYP11B1 levels were also significantly increased by VitD treatment. PTH1R mRNA levels were positively correlated with those of CYP17A1 and CYP11B1, both involved in cortisol production. In addition, the status of VDR was correlated with TRACP-5b levels, and that of PTH1R with serum Ca levels as well as urinary Ca excretion, respectively. Results of our present study did firstly demonstrate that aldosterone-producing cells were more sensitive to the fluctuations of extracellular Ca levels and Ca metabolism could directly influence steroidogenesis, especially "neoplastic" co-secretion of aldosterone and cortisol in APA patients.


Assuntos
Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Cálcio/metabolismo , Hiperaldosteronismo/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Sistema Enzimático do Citocromo P-450/genética , Feminino , Humanos , Hiperaldosteronismo/genética , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Receptores de Calcitriol/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Adulto Jovem
14.
Int J Mol Sci ; 20(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357645

RESUMO

Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland's role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.


Assuntos
Glândulas Suprarrenais/metabolismo , Afeto , Exercício , Pós-Menopausa , Psicoterapia , Esteroides/biossíntese , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Técnicas Projetivas , Avaliação de Sintomas
15.
Int J Mol Sci ; 20(12)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234562

RESUMO

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal ß2-adrenergic receptor (ß2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal ß2-AR antibody. The results show that immunoreactivity for ß2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for ß2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates ß2-AR expression in the human cortex and provides suggestions on the possible involvement of ß2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death.


Assuntos
Glândulas Suprarrenais/metabolismo , Expressão Gênica , Receptores Adrenérgicos beta 2/metabolismo , Adolescente , Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores Adrenérgicos beta 2/genética , Adulto Jovem
16.
Eur J Endocrinol ; 181(3): D15-D26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176302

RESUMO

Notwithstanding the high prevalence of primary aldosteronism (PA), probably the most common form of secondary hypertension, the diagnosis of PA is often neglected or delayed, thus precluding target treatment, which is curative in many cases. For selection of the most appropriate treatment, a fundamental step is the distinction between a lateralized form, mainly aldosterone-producing adenoma (APA), and bilateral adrenocortical hyperplasia (BAH), also known as idiopathic hyperaldosteronism (IHA). To this aim all current guidelines recommend adrenal vein sampling (AVS), a technically challenging procedure that often fails, particularly in non-experienced hands. Cosyntropin (synthetic ACTH) is administered in the attempt to maximize adrenal cortisol secretion and avoid pulsatile adrenocortical hormone secretion in about 40% of the referral centres around the world. However, the Endocrine Society guidelines do not advise about the use or not of cosyntropin as stimulus during AVS, as there are arguments in favour and against its use. These arguments are presented in this debate article reflecting the views of groups that currently use and do not use cosyntropin.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Cosintropina/administração & dosagem , Hiperaldosteronismo/metabolismo , Flebotomia/métodos , Glândulas Suprarrenais/efeitos dos fármacos , Hormônios/administração & dosagem , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico
17.
Endocrinology ; 160(7): 1719-1730, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31166572

RESUMO

The control of steroidogenesis in the neonatal adrenal gland is of great clinical interest. We have previously demonstrated that the postnatal day (PD) 2 rat exhibits a large plasma corticosterone response to hypoxia in the absence of an increase in plasma ACTH measured by RIA, whereas the corticosterone response to exogenous ACTH is intact. By PD8, the corticosterone response to hypoxia is clearly ACTH-dependent. We hypothesized that this apparently ACTH-independent response to hypoxia in the newborn rat is due to an increase in a bioactive, nonimmunoassayable form of ACTH. To evaluate this phenomenon, we pretreated neonatal rats with a novel, specific, neutralizing anti-ACTH antibody (ALD1611) (20 mg/kg or 1 mg/kg IP) on the morning of PD1, PD7, and PD14. Twenty-four hours later, we measured hypoxia- or ACTH-stimulated plasma ACTH and corticosterone. For long-term effects, ALD1611 was given on PD1 and pups were studied on PD8 and PD15. Pretreatment with ALD1611 significantly decreased baseline corticosterone and completely blocked the corticosterone response to hypoxia and exogenous ACTH stimulation at all ages. The effect of 1 mg/kg ALD1611 on PD1 had dissipated by PD15. The decrease in corticosterone in ALD1611-treated pups was associated with decreases in baseline and hypoxia- and ACTH-stimulated adrenal Ldlr, Mrap, and Star mRNA expression at all ages. The adrenal response to hypoxia in the newborn rat is ACTH-dependent, suggesting the release of nonimmunoassayable, biologically active forms of ACTH. ALD1611 is useful as a tool to attenuate stress-induced, ACTH-dependent adrenal steroidogenesis in vivo.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Hormônio Adrenocorticotrópico/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Corticosterona/sangue , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/farmacologia , Animais , Animais Recém-Nascidos , Feminino , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipóxia/metabolismo , Masculino , Fosfoproteínas/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de LDL/metabolismo
18.
J Steroid Biochem Mol Biol ; 192: 105386, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152782

RESUMO

Glucocorticoid is secreted by adrenal cortex, which binds to intracellular glucocorticoid and mineralocorticoid receptors to regulate steroidogenesis-related gene expression and testosterone production in Leydig cells. Glucocorticoid receptor activity shows inhibitory action on Leydig cell steroidogenesis, while mineralocorticoid receptor activity shows the stimulatory action. Leydig cells contain two important glucocorticoid-metabolizing enzymes, 11ß-hydroxysteroid dehydrogenase type 1 and type 2, regulating the intracellular levels of glucocorticoids by a pre-receptor mechanism. 11ß-Hydroxysteroid dehydrogenase type 1 is a bidirectional enzyme, and its direction is regulated by intracellular NADP+/NADPH redox potential. Leydig cells contain many steroidogenic enzymes, possibly regulating NADP+/NADPH redox potential by coupling with 11ß-hydroxysteroid dehydrogenase type 1. Here, we review the 11ß-hydroxysteroid dehydrogenase regulation and possible consequences in Leydig cell biology and pathology.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Glândulas Suprarrenais/metabolismo , Corticosterona/metabolismo , Glucocorticoides/metabolismo , Células Intersticiais do Testículo/metabolismo , Testosterona/metabolismo , Animais , Humanos , Masculino
19.
Clin Nucl Med ; 44(9): 748-749, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31107752

RESUMO

Bilateral adrenal masses were found by ultrasound on a 55-year-old man with sudden onset of chest distress and palpitation after drinking alcohol. After the negative laboratory tests of plasma catecholamine and urinary vanillylmandelic acid, the F-FDG PET/CT revealed extremely intense metabolic activity in the bilateral adrenal lesions, and the subsequent I-meta-iodobenzylguanidine scintigraphy also showed increased radioactivity in the lesions. The pathology of surgery confirmed the diagnosis of bilateral pheochromocytomas.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/metabolismo , Fluordesoxiglucose F18 , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/patologia
20.
Medicina (Kaunas) ; 55(5)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137561

RESUMO

Background and objectives: Intrauterine growth restriction is thought to be implicated in long-term programming of hypothalamic-pituitary-adrenal axis activity. We investigated adrenal function in adolescents born small for gestational age (SGA) in relation to their postnatal growth and cardiovascular parameters. Materials and Methods: Anthropometric parameters, blood pressure, heart rate, dehydroepiandrosterone sulfate (DHEAS), and cortisol levels were assessed in 102 adolescents aged 11-14 years followed from birth (47 SGA and 55 born appropriate for gestational age (AGA)). Results: Mean DHEAS levels were higher in SGA adolescents with catch-up growth (SGACU+), compared with AGA. Second-year height velocity and body mass index (BMI) gain during preschool years were positively related to DHEAS levels. Morning cortisol levels and systolic and diastolic blood pressure were higher in SGA adolescents without catch-up growth (SGACU-) compared with AGA. Second-year BMI gain was inversely, and 2-12 years increase in subscapular skinfold thickness was directly associated with cortisol levels. Size at birth and postnatal growth explained 47.8% and 38.2% of variation in DHEAS and cortisol levels, respectively. Conclusion: Adrenal function in adolescence is affected by prenatal and postnatal growth: small size at birth with postnatal catch-up growth is related to higher DHEAS secretion, whereas increased cortisol levels and blood pressure are higher in short SGA adolescents.


Assuntos
Glândulas Suprarrenais/enzimologia , Retardo do Crescimento Fetal/enzimologia , Crescimento e Desenvolvimento/fisiologia , Adolescente , Glândulas Suprarrenais/metabolismo , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Desidroepiandrosterona/análise , Desidroepiandrosterona/sangue , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Lactente , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Modelos Lineares , Masculino , Fatores Sexuais
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