增食欲素调节下丘脑-垂体-肾上腺轴的研究进展

增食欲素A和增食欲素B是下丘脑神经肽,通过激活两种G蛋白耦联受体发挥作用.增食欲素及其受体表达于下丘脑室旁核和正中隆起,增食欲素受体还表达于脑垂体促皮质激素细胞、肾上腺皮质和髓质.增食欲素能调节摄食、能量代谢平衡、睡醒周期、血压等,还能调节下丘脑-垂体-肾上腺(HPA)轴.现就增食欲素及其受体在HPA轴中枢支和周围支(peripheral branches)的表达及作用机制作一综述.     

增食欲素调节下丘脑-垂体-肾上腺轴的研究进展

增食欲素A和增食欲素B是下丘脑神经肽,通过激活两种G蛋白耦联受体发挥作用.增食欲素及其受体表达于下丘脑室旁核和正中隆起,增食欲素受体还表达于脑垂体促皮质激素细胞、肾上腺皮质和髓质.增食欲素能调节摄食、能量代谢平衡、睡醒周期、血压等,还能调节下丘脑-垂体-肾上腺(HPA)轴.现就增食欲素及其受体在HPA轴中枢支和周围支(peripheral branches)的表达及作用机制作一综述.     

肥胖大鼠前增食欲素原及增食欲素受体基因表达与下丘脑-垂体-肾上腺轴有关

饮食性肥胖大鼠下丘脑前增食欲素原基因表达降低；肾上腺增食欲素受体2mRNA表达上调并且与下丘脑促肾上腺皮质激素释放激素基因表达水平、血皮质酮水平间存在相关性。     

下丘脑-垂体-肾上腺轴及其调节

着重介绍细胞因子，特别是白细胞介素１（ＩＬ１）对下丘脑垂体肾上腺轴（ＨＰＡＡ）功能的影响和调节。给大鼠注射重组ＩＬ１后可观察到ＡＣＴＨ诱导效应；ＩＬ１和ＩＬ６也能使离体下丘脑组织释放ＣＲＨ。在亚细胞水平，ＩＬ１诱导的原癌基因ｃｆｏｓ表达，可能对室旁核小神经元促肾上腺皮质激素释放激素（ＣＲＨ）的释放有重要意义。ＩＬ１等可通过ＣＲＨ介导间接作用于垂体促肾上腺皮质细胞，也可以直接作用于垂体细胞，但这方面的研究结果尚存在矛盾现象。在体外，ＩＬ１，ＩＬ２，ＩＬ６及肿瘤坏死因子α均可直接刺激肾上腺释放皮质酮；高剂量ＩＬ１β能使下丘脑传入神经已被阻滞或垂体已被切除的动物呈现肾上腺皮质分泌反应。     

下丘脑-垂体-肾上腺轴与重度抑郁症关系的研究进展

<正>重度抑郁症(MDD)主要表现为情绪低落、活动减少、思维减退、认知功能障碍、双相情感障碍等~([1])。世界卫生组织(WTO)专家预测2020年后MDD4将会成为现有疾病中致残和死亡的第二大疾病之一,其终身患病率可以达到15%以上~([2,3]),这将会给全球国家、社会和家庭带来沉重的心理负担和经济负担~([4])。尽管中医药和西药治疗MDD的研究文献很多,但是仍     

下丘脑—垂体—肾上腺轴及其调节

着重介绍细胞因子，特别是白细胞介素－１（ＩＬ－１）对下丘脑－垂体－肾上腺轴功能的影响和调节。给大鼠注射重组ＩＬ－１后可观察到ＡＣＴＨ诱导效应，ＩＬ－１和ＩＬ－６也能使离体下丘脑组织释放ＣＲＨ。在亚细胞水平，ＩＬ－１诱导的原癌基因ｃ－ｆｏｓ表达，可能对室旁核小神经元促肾上腺皮质激素释放激素的释放有重要意义，ＩＬ－１等可通过ＣＲＨ介导间接作用于垂体促肾上腺皮质细胞，也可以直接作用于垂体细胞，但这方面的     

松果腺褪黑素对下丘脑-垂体-肾上腺轴的调节作用

松果腺褪黑素对多种不同功能状态下的下丘脑 垂体 肾上腺轴都有一定调节作用。其机制不仅在于直接与下丘脑 垂体 肾上腺轴上的褪黑素受体结合刺激激素释放 ,并影响糖皮质激素受体的功能 ,而且与五羟色胺、内阿片肽等神经递质、调质相互联系 ;且下丘脑 垂体 肾上腺轴对松果腺褪黑素存在反馈作用。这种调节的广泛性使褪黑素用于内分泌、免疫、精神神经系统疾患的治疗成为可能。     

2型糖尿病患者下丘脑-垂体-肾上腺轴功能改变

糖尿病是一类由遗传、环境、免疫等因素引起的，具有明显异质性的慢性高血糖症及其并发症组成的综合征。近年来，糖尿病与神经内分泌免疫网络的关系已被引起重视，下丘脑-垂体-肾上腺（hypothalamic—pituitary-adrenal，HPA）轴作为一个重要的反馈调节系统，是神经内分泌免疫网络的枢纽，不仅对维持机体内环境平衡起重要作用，而且参与衰老、应激等病理过程。国内外研究发现部分2型糖尿病患者存在不同程度的HPA轴功能失调，HPA轴功能改变在2型糖尿病的发生、发展中可能起重要作用。     

2型糖尿病与下丘脑-垂体-肾上腺轴

2型糖尿病的发生往往由于胰岛素的绝对和(或)相对缺乏,此外还在一定程度上和下丘脑-垂体-肾上腺轴功能改变密切相关。2型糖尿病患者随着下丘脑-垂体-肾上腺轴的改变导致糖皮质激素水平增高,加重了糖代谢和脂代谢紊乱,使糖尿病患者的病情恶化,最终促使糖尿病并发症的发生。     

Seasonal changes in hypothalamic-pituitary-adrenal axis sensitivity in free-living house sparrows (Passer domesticus)

Recent evidence indicates that house sparrows (Passer domesticus) seasonally regulate corticosterone responses to capture, handling, and restraint. Responses during molt and in the fall are lower than responses in the winter and while breeding. This study tested whether changes in either adrenal tissue responsiveness to adrenocorticotropin (ACTH) or pituitary responsiveness to corticotropin releasing factor (CRF) or arginine vasotocin (AVT) could provide the mechanism regulating these seasonal changes. House sparrows were captured at two sites (Massachusetts and New Mexico, USA) and during the above four seasons and injected with exogenous ACTH, CRF, and AVT. ACTH stimulated further corticosterone release in all birds except Massachusetts birds in the winter, suggesting that reduced adrenal sensitivity to ACTH cannot explain reduced corticosterone release during fall and molt. However, exogenous ACTH was less effective during molt at both sites, implying that adrenal sensitivity does change. Pituitary sensitivity also changed seasonally, but these pituitary changes did not match the seasonal changes in corticosterone release. CRF and AVT only succeeded in elevating corticosterone in the spring in Massachusetts birds and in the winter in New Mexico birds, whereas CRF alone also stimulated corticosterone release in New Mexico birds in the fall. Taken together, these data indicate that house sparrows can alter the amount of corticosterone released from adrenal tissue, the amount of ACTH released from the pituitary, and the amount of CRF and AVT released from the hypothalamus, but that none of these changes correlate with seasonal changes in corticosterone release. Consequently, seasonal modulation of corticosterone release in house sparrows appear to result from a complicated mix of adrenal, pituitary, and hypothalamic changes that also vary seasonally.     

2型糖尿病患者皮质醇水平及下丘脑-垂体-肾上腺轴活性

本研究评价2型糖尿病患者皮质醇水平及调节.测定血、尿皮质醇,行地塞米松抑制试验及醋酸可的松试验.糖尿病患者尿皮质醇水平高于正常对照组,其肝脏11β-羟类同醇脱氧酶活性较正常人群明显下降.提示2型糖尿病患者有较高的基础皮质醇水平,其原因可能为肝脏对皮质醇的降解代谢受损.     

A prospective study of the hypothalamic-pituitary-adrenal axis in children with acute lymphoblastic leukemia receiving chemotherapy

Abstract

Background

Glucocorticoids are essential in protocols of therapy of acute lymphoblastic leukemia (ALL).

Objectives

To assess the incidence, severity, morbidity, and risk factors of hypothalamic-pituitary-adrenal axis (HPA) suppression in children with ALL, and the time course of recovery.

Design

Forty standard risk ALL children treated in the Pediatric Hematology/Oncology Unit, Ain-Shams University, Egypt, were classified into dexamethasone (DXM) group: 20 patients on children cancer group protocol and prednisone (PDN) group: 20 patients on modified Berlin-Frankfurt-Muenster (BFM) study group 90 protocol. Patients were followed clinically and by laboratory assessment of morning s.ACTH, basal and after low-dose adrenocorticotrophic hormone stimulation test of cortisol and DHEAS, at diagnosis and every 2 weeks till adrenal recovery.

Results

HPA recovery was earlier in PDN than DXM group (P < 0.05). In induction phases 1 and 2: 65 and 75% of PDN group recovered on week 2, while 45 and 50% of DXM group recovered in week 4. Adrenal recovery was predicted 2 weeks earlier by normalized s.DHEAS. Children below 5 years of age had earlier recovery in PDN group (P = 0.04), no age effect in DXM group.

Conclusion

Adrenal suppression is an inevitable consequence of ALL therapy. Monitoring of cortisol levels and steroid coverage during stress is recommended, and gradual steroid tapering is suggested.     

多囊卵巢综合征患者下丘脑-垂体-肾上腺轴改变与胰岛素抵抗的关系

观察40例多囊卵巢综合征(PCOS)患者基础血和尿皮质醇、垂体激素、稳态模型评估的胰岛素抵抗指数(HOMA-IR)及0.25 mg地塞米松抑制试验后血皮质醇的变化.超重/肥胖的PCOS患者基础和抑制试验后皮质醇水平均升高(P<0.05或P<0.01),提示其糖皮质激素的负反馈调节机制受损,其下丘脑-垂体-肾上腺轴改变与胰岛素抵抗相关.     

11β-HSD1对下丘脑-腺垂体-肾上腺轴及海马的影响

糖皮质激素(GC)受11β-羟类固醇脱氢酶(HSD)1的调节,对大脑活动产生广泛的影响。11-βHSD1催化无活性的11-脱氧皮质酮转化为有活性的GC,从而提高组织局部的GC浓度,加强GC的作用。GC对下丘脑—腺垂体—肾上腺轴的负反馈调节作用受11-βHSD1的影响。海马是与认知、学习、记忆功能密切相关的重要脑区,极易受到随年龄增加的GC神经毒性的损伤。11-βHSD1活性降低有助于减轻与年龄相关的认知障碍。     

阻塞性睡眠呼吸暂停低通气综合征与下丘脑-垂体-肾上腺轴关系研究进展

OSAHS 是一种累及多系统并造成多器官损害的睡眠呼吸障碍性疾病,是高血压、心律失常及心、脑血管等多种严重疾病的独立危险因素。OSAHS 是多因素作用的结果,而近年来研究证实下丘脑-垂体-肾上腺(hypothalamic pituitary adrenal,HPA)轴的功能变化与 OSAHS 发病之间存在密切关系。现就 OSAHS 患者 HPA 轴功能变化及可能的相关机制作一综述。