应激对大鼠海马金属硫蛋白亚型表达的影响

目的 :　观察应激对大鼠海马脑区金属硫蛋白亚型表达的影响。方法 :　以束缚为应激原建立心理应激动物模型。将动物随机分为四组 :正常对照组 (Ctr)、束缚 1 w组 (R1 )、束缚 2w组 (R2 )和束缚 4w组 (R4)。取动物脑和肝脏以镉饱和法测定金属硫蛋白含量 ,取海马组织提取总 RNA,以 RT- PCR检测金属硫蛋白亚型 MT- 1 m RNA和 MT- 3m RNA,并取血测定血浆皮质醇和 IL- 6水平。结果 :　束缚应激后 ,大鼠体重增长明显减慢 ,血浆皮质醇、IL- 6水平显著高于Ctr组 ;海马脑区两种亚型金属硫蛋白 m RNA的表达水平升高 ,脑和肝脏金属硫蛋白含量也明显增加。结论 :　束缚应激可影响海马金属硫蛋白的表达 ,使其在蛋白质水平和 m RNA水平均出现明显升高 ,其可能机制是 ,在应激条件下皮质醇和 IL- 6等因子的上调对这种应激蛋白的表达发挥了诱导作用     

EFFECT OF ARTERIAL CHEMORECEPTOR STIMULATION WITH ALMITRINE BISMESYLATE ON PLASMA RENIN ACTIVITY, ALDOSTERONE, ACTH AND CORTISOL IN ANAESTHETIZED, ARTIFICIALLY VENTILATED CATS

1. Changes in plasma renin activity (PRA) and in the plasma concentration of aldosterone, adrenocorticotrophic hormone (ACTH) and cortisol in response to an intravenous infusion of the chemoreceptor stimulant almitrine bismesylate (0.2 mg/kg) were studied in two groups of anaesthetized, paralysed and constantly ventilated cats. In one group, the peripheral arterial chemoreceptors remained innervated, whereas in the other they were denervated by bilateral cervical vagotomy and section of the carotid sinus nerves. 2. Animals with innervated chemoreceptors (n= 16) reacted to almitrine bismesylate with a significant (P < 0.05) increase in both ACTH and cortisol. These responses were not present in cats in which the peripheral arterial chemoreceptors had been surgically denervated (n= 16). 3. Plasma renin activity and plasma aldosterone increased with time during experiments on both the chemoreceptor-intact and chemoreceptor-denervated cats. Almitrine did not affect the time course of the rise in PRA and plasma aldosterone in either group of animals. 4. These data indicate that, under the conditions of our experiments, almitrine induced arterial chemoreceptor reflex mechanisms stimulate ACTH and cortisol release, but has no chemoreceptor-dependent influence on PRA or plasma aldosterone.     

A longitudinal evaluation of dexamethasone and cortisol plasma concentrations in the dexamethasone suppression test before and during treatment with antidepressant drugs

Thirty depressed in- and outpatients received serial dexamethasone suppression tests (DSTs). Plasma dexamethasone and cortisol concentrations were drawn at 1600 on the day following a 1-mg oral dose of dexamethasone. The first DST was performed after patients were drug-free for a period of 1 week; the second, third, and fourth DSTs while patients received antidepressant medication. Dexamethasone and cortisol concentrations drawn in the drug-free period correlated significantly. The cortisol to dexamethasone ratio changed significantly with time in DST nonsuppressors, suggesting that nonsuppression is associated with an altered pharmacodynamic response of the hypothalamopituitary-adrenal axis to dexamethasone during depression. When dexamethasone concentrations from the drug-free period were compared with those drawn during antidepressant treatment, no significant differences were noted.     

A 5-Day Estradiol Therapy, in Amounts Reproducing Concentrations of the Early-Mid Follicular Phase, Prevents the Activation of the Hypothalamo-Pituitary-Adrenal Axis by Interleukin-1α in the Ovariectomized Rhesus Monkey

In a previous report, we have shown that intracerebroventricular (icv) administration of the cytokine interleukin-1a (IL-1α) in the ovariectomized (OVX) rhesus monkey results in the acute activation of the hypothalamo-pituitary-adrenal (HPA) axis and the inhibition of LH and FSH secretion. Here, we compare the cortisol response to IL-1α administration in OVX monkeys and in OVX animals replaced with estradiol (E) to reproduce E concentrations typical of the early-mid follicular phase. Cortisol, LH and FSH were measured after an icv infusion of physiological saline or IL-1α (2.1 or 4.2 μg/30 min) in both groups. E-containing capsules were implanted sc 5 days prior to the experiment. In OVX, E concentrations were <5 pg/ml. Cortisol concentrations decreased throughout the afternoon after saline infusion (to 49.7 ± 5.1% of baseline at 5 h; n = 7), but increased significantly after IL-1α to 158.3 ± 13.8% (n = 7). In OVXE, cortisol also declined after saline (to 76.4 ± 16.2%; n = 5). There were 2 types of response to IL-1α: in grp 1 (mean E 18.0 ± 0.7 pg/ml), the cortisol response was similar to that in OVX (160.8 ± 17.0%; n = 5), while in grp 2 (E: 30.7 ± 3.1 pg/ml), the cortisol response was absent (66.6 ± 7.2% of baseline at 5 h; NS vs saline in OVXE; n = 7). The cortisol response to IL-1α was restored in 2 monkeys when E was increased to >100 pg/ml, confirming our previous observations. While saline infusion did not affect LH (102.3 ± 10.2% of baseline at 5 h) or FSH (102.5 ± 4.4%) secretion in OVX monkeys, there was a significant decrease in both hormones after IL-1α (LH: 33.3±3.7%, FSH: 66.2 ± 6.5%; P<0.05 vs saline). This effect was lessened in OVXE animals: By 5 h, areas under the LH curve were 62.8 ± 10.9% of baseline in grp 1 and 85.3 ± 7.9% in grp 2 (NS vs saline), while those under the FSH curve were 84.0 ± 6.5% in grp 1 and 77.7 ± 4.3% in grp 2 (NS vs saline). The data demonstrate a striking effect of a 5-day estradiol treatment in preventing the HPA axis response to the cytokine IL-1α in the OVX monkey. This action, however, occurs only within restricted estradiol concentrations that reproduce E levels typical of the early-mid follicular phase of the menstrual cycle. While the precise mechanism through which estradiol exerts this action remains to be investigated, the results may have clinical relevance to the issue of estrogen replacement therapy in physiology and pathology.     

Morning and Evening Adrenocortical Responses to ACTH Stimulation in Endogenously Depressed Patients: A Preliminary Report

Abstract: Adrenocortical stimulation with ACTH both in the morning (M-test) and in the evening (Etest) and the dexamethasone suppression test were carried out in patients suffering from endogenous depression (DEP) and normal controls (NOR). A greater cortisol release in DEP was recognized than in NOR in the M-test, an earlier peak response of DEP was shown in the M-test than in the Etest, and a lack of association between hypersecretion of cortisol during depression and cortisol output after ACTH administration was noted. These findings, together with the results of DST, suggest that excessive activity of the hypothalamic-pituitary-adrenal (HPA) axis in depression may result, partly, from adrenocortical hyperresponsiveness.     

POTENTIATION OF FENFLURAMINE-INDUCED ACTH RELEASE IN MAN BY NALOXONE

1. This study set out to compare the effect of the combination of fenfluramine (Fen) and naloxone (Nal) on ACTH and cortisol release with each of these agents alone in six normal volunteers. Three protocols were used: 1.5 mg/kg bodyweight oral Fen; 125 micrograms/kg bodyweight i.v. Nal; oral Fen plus i.v. Nal 135 min later. Plasma ACTH and cortisol were measured at intervals of 285 min over each test. 2. The mean peak levels and mean peak changes from basal in plasma ACTH and cortisol were significantly greater in the combination test (Fen/Nal) than in either the Fen alone or the Nal alone tests. Fen and Nal given together cause a synergistic release of ACTH and cortisol as determined by the areas under the ACTH-time and cortisol-time curves for Fen/Nal compared to the sums of Fen alone plus Nal alone curves for ACTH and cortisol. 3. We conclude that Fen and Nal acting synergistically work through different and potentiating mechanisms at the hypothalamic, central nervous system and/or pituitary levels to cause ACTH release.     

Biochemical stress responses of striped mullet (mugil cephalus l.) to fluorene analogs

The effects of fluorene, dibenzofuran, carbazole and dibenzothiophene on the mortality and induction of biochemical stress responses in striped mullet (Mugil cephalus L.) were compared to determine whether structural modification alters the toxic effects of these aromatic hydrocarbons. Dibenzofuran was less toxic than the Other analogs and at sublethal concentrations was less effective in the induction of biochemical stress responses. The fluorene analogs caused moderate elevations of plasma cortisol and glucose concentrations but plasma lipids and osmolality were largely unchanged. Marked behavioral disturbances occurred with high concentrations of the analogs which were associated with a depletion of brain biogenic amine stores. The possibility of early detection of environmental contamination by measurement of biochemical stress parameters in fish is discussed.     

针刺前后血浆亮氨酸脑啡肽样物质及皮质醇含量的变化

作者用划表法评定慢痛病人的针刺临床疗效;用弹簧测痛棒测定痛阈,评定针刺对实验痛的镇痛效果;用放射免疫法测定针刺前后血浆亮氨酸脑啡肽样物质(LEKLS)及血浆皮质醇含量的变化,分析两者的变化与针效的关系。结果表明针刺的临床疗效和对实验痛的镇痛效果均与血浆LEKLS含量变化呈正相关,而与血浆皮质醇含量无关。针刺的临床疗效与痛阈的变化一致。     

Inhibition of prolactin and aldosterone secretion by the dopamine derivative ibopamine

Summary In 7 patients with congestive heart failure acute oral administration of ibopamine, a new dopamine derivative, induced a significant decrease in serum prolactin and aldosterone without affecting serum growth hormone or cortisol. The Metoclopramide-induced secretion of prolactin and aldosterone was blunted in 6 patients pretreated with 200 mg ibopamine. The data are consistent with a dopaminergic effect of ibopamine due to a peripheral action, probably on D-2 receptors.