注射IL-1β后大鼠下丘脑室旁核内CRR/AVP基因转录的动态变化

目的 探讨IL-1β对下丘脑室旁核(PVN)内促肾上腺皮质素释放激素(CRH)和血管加压素(AVP)基因转录的影响.方法 麻醉下于Wistar大鼠右心房内留置导管,48 h后将清醒大鼠分为5组,分别于右心房内注射IL-1β(1.4 μg/kg)或生理盐水(300 μ1)后于15、120 min后断头,以及无任何处置的空白对照组.取各组大鼠躯干血,采用放射免疫分析法测定促.肾上腺皮质激素(ACTH)和AVP的浓度.利用[35S]UTP、[35S]CTP双标记RNA探针采用原位杂交组织化学方法检测各组大鼠PVN内CRH hnRNA、CRH mRNA和AVPhnRNA、AVPmRNA的表达.结果 与空白对照组相比,血浆ACTH和AVP浓度均在注射IL-1β 15 min后显著增加(P<0.01),在120 min后恢复正常.CRH hnRNA表达水平在注射IL-1β 15 min后显著增加(P<0.01),120 min后恢复正常;CRH mRNA表达水平在注射IL-1β 120min后显著增加(P<0.01).小细胞内AVP hnRNA表达水平在注射IL-1β 15 min后显著增加(P<0.01),且持续增加至120 min后,而大细胞内AVP hnRNA表达水平在注射IL-1β 120 min后显著增加(P<0.01);小细胞内AVP mRNA表达水平在注射IL-1β120 min后显著增加(P<0.01),而大细胞内AVP mRNA表达水平在注射IL-1β 15和120 min后均无明显改变.结论 共存于小细胞内的CRH、AVP基因转录的调控机制不同,而共存于大、小细胞内的AVP基因转录的调控机制也完全不同,表明不同细胞内同一基因转录的动态变化不同.     

中国劲酒对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴及免疫功能的影响

目的:研究中国劲酒对皮质酮致肾阳虚模型的大鼠下丘脑-垂体-肾上腺(Hypothalamic-pituitary adrenal,HPA)轴及免疫功能的影响。方法:取健康清洁级雄性SD大鼠45只,按随机数字表法分为空白对照组、模型组和中国劲酒组,每组15只,通过皮下注射外源性皮质酮(10 mg/kg体重)连续14天抑制HPA轴,制备肾阳虚模型。皮质酮注射前5天,以50 ml/kg体重灌胃中国劲酒(相当于中国劲酒日推荐服用剂量的30倍),连续19天。采用酶联免疫吸附试验(ELISA)方法检测血浆皮质酮(Corticosterone,CORT)含量;采用放射性免疫法测定血浆中促肾上腺皮质激素(Adrenocorticotropic hormore,ACTH)含量,采用实时定量-聚合酶链反应法(Real-time PCR)测定下丘脑促肾上腺皮质激素释放激素(Corticotropin releasing hormone,CRH)mRNA表达水平;取胸腺称重,淋巴细胞凋亡及增殖率分别采用流式细胞仪法和改良四氮唑盐(XTT)法。结果:在外源性皮质酮作用下,肾阳虚模型大鼠较空白对照组HPA轴和免疫功能受到明显抑制,中国劲酒灌胃后可显著提高大鼠下丘脑CRH mRNA水平、血浆ACTH含量,与肾阳虚模型组比较差异有统计学意义(P<0.05);血浆CORT水平有升高倾向;同时在免疫调节方面,中国劲酒可明显增加皮质酮模型大鼠胸腺重量和降低脾脏淋巴细胞凋亡率,与肾阳虚模型组比较差异有统计学意义(P<0.01);中国劲酒有促进淋巴细胞增殖的趋势。结论:中国劲酒能改善肾阳虚模型大鼠HPA轴功能;也具有改善肾阳虚模型大鼠免疫功能的作用。     

不同应激方式中小鼠下丘脑与垂体中促肾上腺皮质激素释放激素、促肾上腺皮质激素表达与血清糖皮质激素水平的变化规律及加味逍遥丸的调节作用

目的了解心理和生理（小站台水环境复合）应激及纯心理（情绪）应激后不同时间小鼠下丘脑与垂体促肾上腺皮质激素释放激素（CRH）、促。肾上腺皮质激素（ACTH）的表达和血清糖皮质激素（GC）变化规律及加味逍遥丸的调节作用。方法利用小站台水环境装置应激动物和多功能条件反应箱电刺激小鼠激怒,而致试验鼠情绪紧张的纯心理应激方法制造动物模型;中药加味逍遥丸按2mg／g体重灌胃给药;免疫组化法检测CRH、ACTH蛋白;放射免疫法检测血清糖皮质激素含量。结果小站台水环境应激状态下,下丘脑CRH和垂体ACTH的表达面积都于3h明显增多;血清糖皮质激素于12h升高,并随应激时间延长继续升高。加味逍遥丸在小站台水环境应激72h时能减少下丘脑CRH、垂体ACTH的表达面积和降低反应强度,并下调血清糖皮质激素水平。在情绪应激状态下,下丘脑CRH和垂体ACTH表达面积和强度都于1d增多和增强,延长应激时间,下丘脑CRH、垂体ACTH表达和GC含量均维持在1d水平;加味逍遥丸在情绪应激5d时能降低下丘脑CRH表达强度,减少垂体ACTH的表达面积和降低强度,并下调血清糖皮质激素水平。结论小站台水环境应激状态下下丘脑CRH和垂体ACTH表达面积增多和反应强度明显增强;加味逍遥丸对应激造成的下丘脑CRH和垂体ACTH高表达有调节作用。情绪应激状态下下丘脑CRH和垂体ACTH表达面积增多和反应强度明显增强,加味逍遥丸对应激造成的下丘脑CRH和垂体ACTH高表达有调节作用。     

褪黑素对创伤后应激障碍大鼠下丘脑-垂体-肾上腺轴的影响

目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-PCR方法检测下丘脑中促肾上腺皮质激素释放激素(CRH)mRNA的表达,利用酶联免疫吸附试验(ELISA)检测血清中促肾上腺皮质激素(ACTH)、肾上腺素(EPI)和糖皮质激素(GC)的含量。结果:PTSD组大鼠拒俘反应明显(P<0.05),下丘脑中CRH mRNA表达升高(P<0.05),血清中ACTH和EPI明显升高(P<0.05),但是GC水平下降(P<0.05)。MLT治疗后可以明显缓解PTSD大鼠拒俘反应(P<0.05),同时降低下丘脑中CRH mRNA表达(P<0.05),降低血清中ACTH和EPI水平并升高GC的水平(P<0.05)。结论:MLT治疗可缓解PTSD大鼠的症状,并恢复HPA轴的神经内分泌平衡。     

强肌健力饮对肾阳虚大鼠CRH、ACTH、Cor水平的影响

目的:观察强肌健力饮对肾阳虚大鼠下丘脑组织中促肾上腺皮质激素释放激素(CRH)及血浆促肾上腺皮质激素(ACTH)、皮质醇(Cor)水平的影响,进一步探讨该方对中医肾阳虚证的防治机理.方法:将大鼠分为正常对照组、肾阳虚模型组、强肌健力饮低、中、高剂量组、右归丸阳性对照组,采用氢化可的松制备肾阳虚大鼠模型.观察动物的一般状态及其胸腺和肾上腺指数,采用放射免疫分析检测CRH、ACTH、Cor的含量.结果:①肾阳虚模型组大鼠体重及胸腺指数、肾上腺指数明显低于正常对照组(P＜0.01),CRH、ACTH、Cor含量均比正常对照组显著降低(P＜0.01).②强肌健力饮各剂量组CRH、ACTH、Cor含量均比肾阳虚模型组显著升高(P＜0.05～0.01).结论:肾阳虚时下丘脑-垂体-肾上腺轴合成、分泌和调控功能低下,而强肌健力饮能够修复该轴功能的损伤,表明该方药具有下丘脑、垂体、肾上腺轴多层次的调节作用.     

冷适应建立对寒冷暴露大鼠心肌的保护作用

 摘要：【目的】依据不同强度冷刺激大鼠血浆激素水平的改变建立冷适应性模型，为研究寒冷适应性保护机制奠定基础。【方法】60只SD大鼠分成3组每组20只。对照组，4℃冷刺激4h/d组，0℃冷刺激10h/d组。高效液相检测血浆儿茶酚胺，放射免疫法检测血浆皮质醇换算成皮质酮含量。观察大鼠冷适应后寒冷暴露血浆LDH,CK-MB ,心肌髓过氧化物酶（MPO）活性。【结果】不同强度冷刺激大鼠血浆糖皮质激素、儿茶酚胺的分泌水平不同组间比较（P＜0.01），建立冷适应模型。冷适应处理大鼠寒冷暴露组血浆LDH、CK-MB和心肌MPO活性显著低于寒冷暴露组（P＜0.05）。【结论】建立了冷适应大鼠模型，冷适应能够降低寒冷暴露所造成的心肌损伤。     

注射IL-1β后大鼠下丘脑室旁核内CRH／AVP基因转录的动态变化

目的 探讨IL-1β对下丘脑室旁核（PVN）内促肾上腺皮质素释放激素（cRH）和血管加压素（AVP）基因转录的影响。方法麻醉下于Wistar大鼠右心房内留置导管,48h后将清醒大鼠分为5组,分别于右心房内注射IL-1β（1．4μg／kg）或生理盐水（300μl）后于15、120min后断头,以及无任何处置的空白对照组。取各组大鼠躯干血,采用放射免疫分析法测定促肾上腺皮质激素（ACTH）和AVP的浓度。利用[35S]UTP、[35S]CTP双标记RNA探针采用原位杂交组织化学方法检测各组大鼠PVN内CRHhnRNA、CRHmRNA和AVPhnRNA、AVPmRNA的表达。结果与空白对照组相比,血浆ACTH和AVP浓度均在注射IL-1β15min后显著增加（P〈0．01）,在120min后恢复正常。CRHhnRNA表达水平在注射IL-1β15min后显著增加（P〈0．01）,120min后恢复正常;CRHmRNA表达水平在注射IL-1β120min后显著增加（P〈0．01）。小细胞内AVPhnRNA表达水平在注射IL-1β15min后显著增加（P〈0．01）,且持续增加至120min后,而大细胞内AVPhnRNA表达水平在注射IL-1β120min后显著增加（P〈0．01）;小细胞内AVPmRNA表达水平在注射IL-1β120min后显著增加（P〈0．01）,而大细胞内AVPmRNA表达水平在注射IL-1β15和120min后均无明显改变。结论共存于小细胞内的CRH、AVP基因转录的调控机制不同,而共存于大、小细胞内的AVP基因转录的调控机制也完全不同,表明不同细胞内同-基因转录的动态变化不同。     

鼠重组白细胞介素—1对小鼠下丘脑—垂体—肾上腺轴的影响

探讨重组白细胞介素（rIL-1)对下丘脑－垂体肾上轴的作用。采用rIL-1静脉注入（C组注入前用抗－HRH血清预处理）,测定注入rIL-1后不同时间CRH、ACTH及CORT血浆含量变化。结果表明,rIL-1可使CRH,ACTH,CORT血浆含量有不同水平的升高（B组）,预先注射抗－CRH血清可阻断该效应（C组）,说明rIl-1对HPAA的激活作用是通过CRH介导的。     

促肾上腺皮质激素对慢性痛大鼠痛行为和海马内BDNF、CRF水平的影响

目的与方法:采用痛行为评分方法、免疫组化和原位杂交技术,观察促肾上腺皮质激素(ACTH)对完全福氏佐剂所致的关节炎大鼠海马内脑源性神经营养因子(BDNF)及其功能性受体trkB和促肾上腺皮质激素释放激素(CRH)水平的影响。结果:关节炎大鼠的痛行为评分显著高于正常对照组,同时注射侧对侧海马内BDNF免疫活性(IR)神经元、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数在注射佐剂后 2 4h显著高于正常对照组,而腹腔注射ACTH(2 5IU/kg或 12 5IU/kg)后,上述指标显著低于关节炎组;摘除双侧肾上腺后,腹腔注射ACTH的关节炎大鼠对侧海马内BDNF-IR、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数明显高于未摘除肾上腺的关节炎组。结论:海马内的BDNF和CRH参与慢性痛的调制,ACTH能抑制海马内BDNF和CRH的升高而产生镇痛作用,肾上腺对ACTH发挥其功能起决定性作用.     

中枢CRH在大鼠应激性体温升高和LPS性发热机制中的作用

目的:进一步观察中枢促肾上腺皮质激素释放激素(CRH)在大鼠应激性体温升高和脂多糖(LPS)性发热中枢机制中的作用。方法:第三脑室微量注射CRH受体拮抗剂α-helicalCRH(9-41)和LPS,测定大鼠结肠温度及脑腹中隔区精氨酸加压素(AVP)含量。结果:生理盐水对照组大鼠体温明显升高,最大升幅为(0.88±0.31)℃。第三脑室注射CRH受体拮抗剂α-helicalCRH(9-41)10min后再注射生理盐水组,90min内大鼠结肠温度未见明显波动,90min后体温开始上升,1.5h体温反应指数(TRI_1.5)明显低于生理盐水对照组,而脑腹中隔区AVP含量和TRI_3.5与对照组比较均没有明显差别。第三脑室注射300ng的LPS引起大鼠结肠温度双相性升高,其TRI_3.5明显高于生理盐水对照组。事先向第三脑室注射α-helicalCRH(9-41)(5μg)再注射LPS组,TRI_3.5明显高于LPS组,而脑腹中隔区AVP含量明显低于LPS组。结论:CRH介导应激诱导的早期体温升高。CRH可能通过诱导脑腹中隔区AVP的生成限制大鼠LPS性发热。在大鼠LPS性发热中,CRH可能是一种双相作用分子,一方面本身介导发热体温升高,另一方面又诱生发热体温负调节介质而限制发热体温的升高。     

Effect of acute ether or restraint stress on plasma corticotropin-releasing hormone, vasopressin and oxytocin levels in the rat

Ether and restraint stress-induced peripheral plasma corticotropin releasing hormone (CRH), arginine vasopressin (AVP), oxytocin (OXY) and adrenocorticotropin (ACTH) levels were measured by radioimmunoassays. Plasma CRH, AVP, OXY and ACTH rose to approximately twice the level of control rats 2 min after the onset of a 1-min exposure to ether. Plasma CRH rose further 5 min after the onset of ether stress, while plasma AVP and OXY returned to the baseline levels at 5 min. Plasma CRH, OXY and ACTH showed significant elevation 2 min after the onset of restraint stress, while plasma AVP did not show a significant change. Plasma OXY and ACTH rose further 5 min after the onset of restraint stress, whereas plasma CRH returned to baseline levels. CRH and OXY concentrations in the hypothalamic median eminence decreased 5 min after the onset of ether exposure and restraint, while the AVP concentration did not differ from control levels. The results, including the discrepancy between plasma CRH and ACTH 5 min after stress, suggest that CRH in the peripheral plasma is derived from both hypothalamic and extrahypothalamic tissues. The levels of stress-induced CRH in the peripheral plasma were sufficient to stimulate ACTH release. These results suggest that ether and restraint stress elevate plasma CRH shortly after the onset of the stress, and that this elevation in the plasma CRH level is at least partly responsible for stress-induced ACTH secretion.     

Prolonged reduction of motion sickness sensitivity by visual-vestibular interaction

The angular vestibulo-ocular reflex (aVOR) and optokinetic nystagmus (OKN) were elicited simultaneously at low frequencies to study effects of habituation of the velocity storage time constant in the vestibular system on motion sickness. Twenty-nine subjects, eleven of whom were susceptible to motion sickness from common transportation, were habituated by sinusoidal rotation at 0.017?Hz at peak velocities from 5 to 20°/s, while they watched a full-field OKN stimulus. The OKN stripes rotated in the same direction and at the same frequency as the subjects, but at a higher velocity. This produced an OKN opposite in direction to the aVOR response. Motion sickness sensitivity was evaluated with off-vertical axis rotation (OVAR) and by the response to transportation before and after 5?days of visual-vestibular habituation. Habituation did not induce motion sickness or change the aVOR gains, but it shortened the vestibular time constants in all subjects. This greatly reduced motion sickness produced by OVAR and sensitivity to common transport in the motion susceptible subjects, which persisted for up to 18?weeks. Two motion susceptible subjects who only had aVOR/OKN habituation without being tested with OVAR also became asymptomatic. Normal subjects who were not habituated had no reduction in either their aVOR time constants or?motion sickness sensitivity. The opposing aVOR/OKN stimulation, which has not been studied before, was well tolerated, and for the first time was an effective technique for rapid and prolonged habituation of motion sickness without exposure to drugs or other nauseating habituation stimuli.     

Exendin-4, a GLP-1 receptor agonist,stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect

Exendin-4 (Ex4) is a potent and long-lasting agonist of glucagon-like peptide-1 (GLP-1), which has been previously found to stimulate pituitary-adrenal axis in the rat. Aim of the present study was to gain insight into the mechanism(s) involved in the Ex4-induced rise in the rat plasma concentrations of ACTH, aldosterone and corticosterone. Preliminary time- and dose-response studies showed that the maximum stimulating effect of Ex4 occurred within 1 or 2 h and at dose ranging from 0.5 to 2.0 nmol/100 g body weight. The GLP-1 receptor (GLP-1R) antagonist Ex(9-39) did not significantly affect ACTH, aldosterone and cortico-sterone responses to Ex4. Neither the administration of CRH and arginine vasopressin (AVP)-receptor antagonists nor adrenal demedullation prevented pituitary-adrenal axis responses to Ex4. The prolonged (4 or 6 days) suppression of the pituitary ACTH release by dexamethasone impaired corticosterone, but not aldosterone response to Ex4. The following conclusions are drawn: i) Ex4 stimulates rat pituitary-adrenal axis through receptors other than the classic GLP-1R; ii) neither CRH and AVP nor medullary catecholamines are involved in the Ex4-induced stimulation of ACTH release; iii) ACTH stimulation accounts for the rise in corticosterone plasma concentration; and iv) the aldosterone secretagogue effect of Ex4 occurs via a mechanism independent of the stimulation of either ACTH or medullary catecholamines.     

急性高台应激对大鼠神经内分泌激素、相关受体及脑神经递质的影响

目的 高台应激是一种不可逃避应激,是研究应激对机体神经生理病理变化的重要模型.本研究对急性高台应激后神经内分泌激素、受体表达、脑神经递质变化以及地西泮的干预作用进行探讨.方法 大鼠随机分为空白对照组、应激+地西泮(DAP)组与应激+溶剂组.后两组于应激前30 min分别腹腔注射地西泮2 mg/kg与等量生理盐水.采用酶联免疫法测量应激后各组的血浆促肾上腺皮质激素(ACTH)、血清皮质酮(CORT)水平;采用实时定量PCR测量下丘脑促肾上腺皮质激素分泌激素(CRH)mRNA、海马糖皮质激素受体(GR)mRNA、盐皮质激素受体(MR) mRNA、5-羟色胺1a受体(5-HT1aR)mRNA水平;采用高效液相色谱电化学法测量大脑皮层匀浆液中去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)水平.结果 与空白组相比,应激+溶剂组大鼠血浆ACTH、血清CORT以及海马5-HT1aR mRNA水平升高(P均＜0.05),此变化可由DAP逆转(P均＜0.05).此外,DAP还可降低应激后的下丘脑CRH mRNA,海马GR mRNA以及MR mRNA水平(P均＜0.05).然而大脑皮层匀浆液中NE、DA、5-HT、5-HIAA在应激后无变化.结论 急性高台应激可引起大鼠相关神经内分泌激素与受体表达变化,且该效应可被DAP逆转.     

围绕两轴进行复杂的旋转刺激后大鼠全脑内Fos的表达(英文)

为了探讨旋转刺激与运动病发生的关系,本研究利用一种复杂的围绕两轴旋转的加速度刺激器刺激大鼠后,观察大鼠全脑内Fos蛋白的表达情况。动物被随机地分成四组,即正常对照组、两轴旋转刺激组、双侧迷路毁损组以及双侧迷路毁损后接受旋转刺激组。采用免疫组织化学染色方法观察全脑不同核团内Fos蛋白的表达情况。结果显示:(1)正常对照组和双侧迷路毁损组大鼠的脑内均未检测到Fos样免疫阳性产物;(2)两轴旋转刺激组的大鼠在给予复杂的围绕两轴旋转的加速度刺激后,在大鼠脑和脑干的多个核团内均可检测到Fos样免疫阳性神经元,其阳性产物主要表达于细胞核。其中在脑干内的前庭复合体的不同亚核(包括前庭内侧核、前庭上核和前庭下核),孤束核、蓝斑核、臂旁内侧核、臂旁外侧核,间脑的室旁核以及边缘系统的杏仁核等内均可观察到密集分布的Fos样免疫阳性神经元;(3)双侧迷路毁损组大鼠在接受复杂的围绕两轴旋转刺激后,在上述相应核团内均难以检测到Fos蛋白的表达。以上研究结果提示两轴旋转刺激可以有效地激活前庭神经元,而大鼠在接受前庭刺激后,脑和脑干的许多核团内大量的神经元可能通过与前庭核复合体发生直接或间接的纤维联系也被激活,这些被激活的神经元可能与运动病发生的复杂机制有关。     

Effects of chronic stress on plasma corticosterone, ACTH and prolactin

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the “stressed” group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.     

Decreased Fos protein expression in rat caudal vestibular nucleus is associated with motion sickness habituation

We investigated the temporal change of Fos protein expression in the caudal vestibular nucleus of rats exposed to daily 2-h Ferris-wheel like (FWL) rotation. Repeated rotation (2 h daily for 14 consecutive days) caused an initial increase in defecation, followed by a gradual decline back to the baseline level after 8 rotation sessions. Unlike defecation, the Kaolin consumption of rats showed a bitonic function during the daily rotation sessions (2 h daily for 33 consecutive days) and finally recovered to the baseline after about 31 sessions. Immunohistochemistry study revealed increased Fos immunolabeled (Fos-LI) neurons in the medial vestibular nucleus and spinal vestibular nucleus during the initial 7 rotation sessions, and it decreased to the baseline level after 10 rotation sessions. There was a strong linear relationship between the amount of Fos-LI neurons and rat defecation level throughout the whole rotation sessions. These results suggest that the change of neuronal plasticity in the caudal vestibular nucleus might contribute to attenuation of gastrointestinal symptoms during motion sickness habituation process.     

Histological and morphofunctional parameters of the hypothalamic–pituitary–adrenal system are sensitive to daidzein treatment in the adult rat

The isoflavone, daidzein is a biologically active, plant-derived compound that interacts with estrogen receptors. Data from previous studies have suggested that daidzein exerts beneficial effects in many diseases; however, as an endocrine disrupter, it may also alter the functioning of the endocrine system. Data regarding the effect of daidzein on the morphofunctional and histological parameters of the hypothalamic–pituitary–adrenal (HPA) system is still lacking. Therefore, using the newCAST stereological software, we investigated the effects of chronic (21 days) daidzein treatment on corticotropin-releasing hormone (CRH) neurons within the hypothalamus and corticotropes (ACTH cells) in the pituitary, while image analysis was employed to-examine the intensity of fluorescence of CRH in the median eminence (ME) and adrenocorticotropin hormone in the pituitary in adult orchidectomized (Ovx) rats. Circulating ACTH and corticosterone levels were also analyzed. This study showed that daidzein treatment decreased the volume density of CRH neurons within the paraventricular nucleus as well as CRH immunofluorescence in the ME. The total number of ACTH cells was decreased, while ACTH cell volume and the intensity of ACTH fluorescence were increased following daidzein treatment. Both ACTH and corticosterone blood levels were increased after daidzein administration. The results of performed experiments clearly demonstrate that volume density of CRH neurons; total number and volume of ACTH cells, as well as stress hormones levels are vulnerable to the effects of daidzein.     

The role of vasopressin in the nicotine-induced stimulation of ACTH and cortisol in men

Summary Experimental evidence indicates that arginine vasopressin (AVP) contributes to the release of ACTH under certain conditions. The present study investigates the role of vasopressin as a secretagogue of ACTH during cigarette smoking or nicotine infusion with additional injection of corticotropin releasing hormone (CRH) and using the specific AVP antagonist d(CH₂)₅Tyr(Me)-AVP. We first tested the effect of the AVP antagonist (10 g/kg body weight i.v.) on ACTH and cortisol release following cigarette smoking in 15 healthy young male smokers. Smoking led to marked increments in plasma nicotine and to a small rise in plasma ACTH and cortisol. Mean plasma ACTH and cortisol levels were at no time significantly altered by the antagonist. This might be due to a slight agonistic effect of the AVP antagonist, to high interindividual variability of the ACTH and cortisol responses after smoking or to a neglegible role of AVP in smoking-induced ACTH release. In a second study we performed the following tests in six healthy male non-smokers: (1) nicotine infusion (1.0 g/kg body weight per min); (2) CRH i.v. (100 g); (3) AVP antagonist i.v. (5 g/ kg); (4) nicotine infusion plus CRH i.v.; (5) nicotine infusion plus AVP antagonist i.v. ; (6) nicotine infusion plus CRH and AVP antagonist i.v.; and (7) sham infusion. Nicotine infusion led to greater increments of AVP, ACTH and cortisol than smoking without causing nausea. Peak nicotine levels after nicotine infusion were lower than after smoking. The AVP antagonist in the reduced dosage given alone had no effect on hormone levels. However, it slightly attenuated the effect of nico tite on ACTH and cortisol (P<0.05, ANOVA). Nicotine and CRH given together stimulated AACH and cortisol in a less than additive manner. The combined effect of nicotine and CRH was not inhibited by the antagonist. Our results indicate that the effect of nicotine on ACTH and cortisol may be partly mediated by hypothalamic AVP. Nicotine may also enhance CRH release by stimulating acetylcholine receptors of hypothalamic CRH neurons.Abbreviations ACTH adrenocorticotropic hormone - ANOVA analysis of variance - AVP arginin vasopressin - CRH corticotropin releasing hormone - K⁺a potassium; d (CH₂)₅ Tyr(Me)- - AVP vasopressin (V₁)-antagonist Supported by a grant from Forschungsrat Rauchen und Gesundheit