Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids / 生理学报

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

A pilot study on hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism.

Background & objectives: Parathormone (PTH) and calcium, both have been shown to stimulate adrenal steroidogenesis in animal models and in vitro experiments. This is attributed to structural similarity between 15-25 amino acid region of the parathyroid hormone (PTH) and 1-11 amino acid region of adrenocorticotropin (ACTH). However, there are no in vivo human data regarding the effect of PTHcalcium axis on adrenocortical function. Materials: Ten patients with primary hyperparathyroidism underwent evaluation for cortisol dynamics including 0800 h and 2000 h plasma cortisol on day 1, cortisol response to insulin induced hypoglycaemia (IIH) on day 2, and 1 mg overnight dexamethasone suppression test (ONDST) on day 4. Serum aldosterone was also measured at 0800 h in fasting state on salt ad libitum for three days. These parameters were repeated 3 months after curative parathyroidectomy. Results: Basal plasma cortisol level at 0800 h and 2000 h were within upper normal range and loss of circadian rhythm in cortisol secretion was observed in half and forty per cent of patients had nonsuppressibility with ONDST. The defined peak cortisol response to insulin induced hypoglycaemia (>550 nmol/l) was achieved in all and nearly one third of patients had exaggerated response (>2000 nmol/l). After curative parathyroidectomy, the abnormalities in circadian rhythm and non-suppressibility with ONDST continued to prevail in 40 per cent of patients. The peak cortisol response to IIH showed a decrement but remained higher than normal. No correlation was observed between circulating parathyroid hormone and calcium with cortisol levels. Serum aldosterone was in upper normal range pre - and postoperatively, though it decreased postoperatively, but it could not attain a statistical significance (p = 0.5). Interpretation & conclusion: Abnormalities in hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism do occur, however these are inconsistent and do not recover in majority of patients even after 3 months of curative parathyroidectomy.

Comparisons between Macroadenomas and Microadenomas in Cushing's Disease: Characteristics of Hormone Secretion and Clinical Outcomes

It has been suggested that the patients with Cushing's disease secondary to pituitary macroadenomas (>10 mm) have higher basal adrenocorticotropic hormone (ACTH) levels, which are less suppressible on high-dose dexamethasone suppression tests (HDDST). We compared the clinical and biochemical characteristics of patients with macroadenomas (N=7) and microadenomas (N=23) who were diagnosed at Samsung Medical Center in Korea between 1996 and 2006. Basal morning plasma ACTH levels were 101.5+/-23.2 pg/mL for macroadenoma patients and 83.6+/-11.1 pg/mL for microadenoma patients (mean+/-SEMs) (p=0.44). Morning serum cortisol levels were 26.8+/-3.2 microgram/dL for macroadenoma patients and 29.5 +/-2.9 microgram/dL for microadenoma patients (p=0.77). The proportion of patients who showed suppressibility on HDDST was almost identical in the two groups (71.4% [5/7] for macroadenoma patients vs. 72.7% [16/22] for microadenoma patients, p=1.00). Furthermore, the remission rate with trans-sphenoidal surgery was similar between the two groups (100% [5/5] for macroadenoma patients vs. 73.3% [11/ 15] for microadenoma patients, p=0.53). Thus, tumor size is not a major determinant of hormone secretion or clinical outcomes in patients with Cushing's disease.

Morphological analysis of neonates of rats treated with dexamethasone in the initial phase of pregnancy / Análisis morfológico de neonatos de ratas tratadas con dexametasona en fase inicial de la preñez

The glucocorticoid dexamethasone has been largely used due to its anti-inflammatory effect. However, several authors report that the excessive exposition to it during pregnancy may cause a retard in the development in several tissues, mainly: liver, lungs and kidneys. But, the majority of the works are done with the application of dexamethasone in the late periods of pregnancy. Because of the lack of researches that evaluate the effects in the beginning of gestation, this paper aimed at evaluating the effect of dexamethasone administered in the initial phase of pregnancy, over the morphology of neonates rat. It was used 10 albino rats (Rattus norvegicus albinus) aged 90 days from the lineage Wistar. The female were coupled and divided in two groups: Group I - rats not submitted to the dexamethasone application (control); Group II - rats submitted to the dexamethasone application in the first 5 days of pregnancy. The results show that the treatment with dexamethasone in a dosage of 0.8mg/Kg during the 5 first days of pregnancy does not produces a weight and height reduction or malformation in the offspring, it does not cause changes in the development of the liver and kidneys of neonate rats, but it leads to a reduction in the denseness of the interalveolar septa causing a higher distension of the alveoli.

El glucocorticoide dexametasona ha sido ampliamente utilizado en virtud de su potencial antiinflamatorio. Sin embargo, varios autores relatan que la exposición excesiva a la dexametasona durante la preñez puede causar el retardo del desarrollo de varios tejidos, principalmente hígado, pulmones y riñones. La mayoría de los trabajos son llevados a cabo con la aplicación de dexametasona en los períodos tardíos de la gestación. El objetivo del trabajo fue evaluar el efecto de la dexametasona, sobre la morfología de ratones neonatos, administrada en la fase inicial de la preñez. Fueron utilizadas 10 ratas Wistar albinas (Rattus norvegicus albinus) con 90 días de edad. Las hembras fueron apareadas y divididas en dos grupos: Grupo I- ratas no sometidas a la dexametasona (grupo control) y Grupo II - ratas sometidas a la aplicación de dexametasona durante los cinco primeros días de preñez. Los resultados mostraron que el tratamiento con dexametasona en dosis de 0,8mg/Kg, a lo largo de los cinco primeros días de la preñez, no produce reducción de peso, longitud o malformación en la prole, tampoco causa alteraciones en el desarrollo del hígado y riñones en los ratones neonatos, pero sí reduce el grosor de los septos interalveolares, causando de esta manera, mayor distensión de los alvéolos.

Postnatal regulation of glucocorticoid receptor in the liver of chicken.

The specific binding of [3H]-dexamethasone to glucocoticoid receptor (GR) and activation of hormone-receptor (H-R) complexes from the liver of chicken at day 0, 5, 10, 30, 60 and 90 were investigated to find out GR regulation during postnatal development. Results showed that GR level (fmol/mg protein) reached a peak by day 5 of postnatal age and was significantly higher (+ 42%) than observed at day-0 (day of hatching), as evidenced also by protein blot experiments and Scatchard analysis of binding data. The GR concentration declined gradually up to day 30, and thereafter, no significant change was observed at day 60 and 90 of postnatal ages. The temperature and salt-dependent activation of GR showed no significant differences in 0 and 30-day old chicken, as determined by DNA-cellulose binding assay. However, nuclear binding of temperature and salt-activated GR complexes was significantly higher in 0-day old chicken. Cross-mixing experiments (wherein nuclei of day-0 were incubated with the H-R complexes of day-30 and vice-versa) revealed the role of nuclear specificity in higher binding of temperature and salt-activated H-R complexes at day-0 of postnatal age. DNase I extraction of nuclei bound to activated H-R complexes showed higher extractability at day-0 (70%), compared to day-30 (44%). Above findings suggested that changes in GR concentration as well as chromatin organization might play an important role in glucocorticoid-mediated responses during postnatal development of chicken.

Respuestas multihormonales a una serie de pruebas neuroendocrinas en psiquiatría: una aproximación multivariada / Multihormonal responses to a series of neuroendocrine challenges in psychiatry: a multivariate approach

Mediante una batería neuroendocrina que incluye la prueba de supresión por dexamotasona, la prueba de estimulación con TRH y respuestas hormonales a apomorfina (PRL, GU, ACTH y cortisol) se estudian 86 pacientes hospitalizados, sin medicación, con los diagnósticos según DSM-IV con Depresión Mayor, esquizofrenia y trastorno esquizoafectivo y 18 controles. Se establecen las diferencias hormonales de los diversos grupos clínicos mediante el análisis factorial de correspondencia, lo que permite formular las posibles procesos fisiopatológicos subyacentes y la identificación de terapias farmacológicas apropiadas. Los resultados sugieren una disregulación cronobiológica del eje hipotálamo-hipófisis-tiroides en la depresión y una disregulación dopaminérgica en presencia de síntomas psicóticos productivos

Afinidade da ligaçäo do deflazacort aos receptores de glicorticóide / Binding affinity of deflazacort to glucocorticoid receptors

O deflazacort (DF) é um glicocorticóide mais potente que prednisolona (P) como agente anti-inflamatório e timolítico. Utilizando como sonda radioativa (3H) dexametazona e concentraçöes crescentes de vários esteróides frios, determinamos a afinidade do DF e da P ao receptor de glicocorticóide presente em citosol de fígado, timo e hipófise de ratos adrenalectomizados. Verificamos que nos três tecidos examinados, há correlaçäo entre as afinidades determinadas e os efeitos timolítico e anti-inflamatório