维吾尔药神香草调节哮喘大鼠下丘脑-垂体-肾上腺轴功能紊乱的实验研究

目的:观察维吾尔药(维药)神香草对哮喘大鼠模型神经内分泌免疫网络若干组分的影响。方法:取雄性健康Wistar大鼠50只,随机分为正常对照组,哮喘模型组,神香草低、中、高剂量治疗组。采用致敏和雾化的方法制备哮喘模型。采用酶联免疫吸附试验(ELISA)方法检测血清中白介素-4(IL-4)、白介素-6(IL-6)、干扰素-γ(IFN-γ)、皮质酮(CORT)水平;放免法检测血浆中促肾上腺皮质激素(ACTH)的含量;采用实时定量-聚合酶链反应(RT-PCR)法测定下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达水平。结果:哮喘反复发作时,大鼠下丘脑-垂体-肾上腺(HPA)轴紊乱,哮喘大鼠下丘脑CRH mRNA表达和血浆ACTH无明显变化,实验各组血清CORT水平升高(P<0.05),神香草高剂量组血清CORT含量高于低剂量组(P<0.05)。细胞因子IFN-γ无明显变化,IL-6、IL-4有下降趋势(P<0.05)。结论:哮喘反复发作的大鼠存在NEI网络的紊乱;神香草可以增强下丘脑-垂体-肾上腺皮质(HPA)轴的功能,改善细胞因子的平衡。这些可能是其治疗哮喘的机制之一。     

维吾尔药神香草调节哮喘大鼠下丘脑-垂体-肾上腺轴功能紊乱的实验研究

目的：观察维吾尔药（维药）神香草对哮喘大鼠模型神经内分泌免疫网络若干组分的影响。方法：取雄性健康Wistar大鼠50只,随机分为正常对照组,哮喘模型组,神香草低、中、高剂量治疗组。采用致敏和雾化的方法制备哮喘模型。采用酶联免疫吸附试验（ELISA）方法检测血清中白介素-4（IL^4）、白介素-6（IL-6）、干扰素-γ（IFN-γ）、皮质酮（CORT）水平;放免法检测血浆中促肾上腺皮质激素（ACTH）的含量;采用实时定量-聚合酶链反应（RT—PCR）法测定下丘脑促肾上腺皮质激素释放激素（CRH）mRNA表达水平。结果：哮喘反复发作时,大鼠下丘脑-垂体-肾上腺（HPA）轴紊乱,哮喘大鼠下丘脑CRHmRNA表达和血浆ACTH无明显变化,实验各组血清CORT水平升高（P〈0．05）,神香草高剂量组血清CORT含量高于低剂量组（P〈0．05）。细胞因子IFN-γ无明显变化,IL-6、IL-4有下降趋势（P〈0．05）。结论：哮喘反复发作的大鼠存在NEI网络的紊乱;神香草可以增强下丘脑．垂体．肾上腺皮质（HPA）轴的功能,改善细胞因子的平衡。这些可能是其治疗哮喘的机制之一。     

肝郁脾虚证模型大鼠下丘脑- 垂体- 肾上腺皮质的变化

目的：探讨复合造模法复制肝郁脾虚证大鼠模型的HPA轴变化及特点。方法：大鼠采用慢性束缚＋过度疲劳＋饮食失节法,连续三周,自然恢复一周。观察造模期间各不同时间点大鼠肾上腺重量及指数、下丘脑促肾上腺皮质激素释放激素（CRH）、血浆促肾上腺皮质激素（ACTH）及皮质酮（CORT）的变化。结果：与正常组比较,模型大鼠肾上腺重量第一周显著增加（P〈0．001）,第三、四周显著减低（P〈0．001和P〈0．01）,其肾上腺指数在实验各周均显著高于正常组（P〈0．05和P〈0．01）;下丘脑CRH第三周显著低于正常组（P〈0．05）,第四周回升并显著高于正常组（P〈0．05）;血浆ACTH在第一、三、四周均显著降低（P〈0．05）;血浆CORT第一周显著降低（P〈0．05）,第二周有所回复,第三、四周仍显著降低（P〈0．05和P〈0．001）。结论：该肝郁脾虚证大鼠模型存在HPA轴的功能减低,垂体对上位激素调节的反应能力减低可能是该模型的一个重要的生物学特征。     

冷暴露长爪沙鼠下丘脑-垂体-肾上腺轴对产热的调节

为探讨下丘脑 -垂体 -肾上腺轴在野生小哺乳动物产热中的调节作用 ,对正常及肾上腺去除的长爪沙鼠进行了冷暴露研究。正常雄性长爪沙鼠在急性冷暴露 ( 4± 1℃ ,1天 )条件下 ,下丘脑促肾上腺皮质激素释放激素的合成和释放没有显著变化 ,肾上腺皮质酮含量增加 4 5 8% ,差异显著 ,血清皮质酮水平有增加趋势 ;慢性冷暴露 ( 4± 1℃ ,3周 )后 ,肾上腺皮质酮含量增加到对照的 2 14倍 ,血清皮质酮含量维持较高水平。肾上腺去除的长爪沙鼠冷暴露 3周后 ,褐色脂肪组织 (BAT)产热 (细胞色素C氧化酶活力、线粒体GTP结合数量 )增加 ,下丘脑促甲状腺激素释放激素的合成和释放、血清三碘甲腺原氨酸水平以及血清去甲肾上腺素的浓度均有增加的趋势。表明冷暴露条件下长爪沙鼠肾上腺皮质酮的合成和释放增加 ,从而抑制BAT的产热 ,皮质酮对BAT产热的抑制部分是通过抑制下丘脑 -垂体 -甲状腺轴激素的合成和分泌以及抑制交感神经系统的活动而实现的。     

低氧暴露对大鼠下丘脑CRF分泌的影响

目的和方法：利用人工模拟低氧及放射免疫测定（RIA）法,观察不同低氧（5km,7km）暴露对大鼠下丘脑分泌促肾上腺皮质激素释放激素（C orticotropin-releasing factor,CRF）的作用和血浆皮质酮水平的变化。比较低氧暴露不同时间（2h,24h,5d,15d）后,大鼠下丘脑CRF分泌和血浆皮质酮的变化。结果：低氧暴露2h,24h后下丘脑的CRF分泌明显增加,血浆皮质酮水平显著升高,这种变化随着低氧程度的加深而增强,随着低氧暴露时间的延长（5d）上述变化减弱。至慢性低氧暴露15d后,下丘脑CRF分泌及血浆皮质酮水平与对照组相比已无显著差异,基本恢复到对照水平。结论：动物暴露于低氧环境后,下丘脑CRF分泌及血浆皮质酮水平变化为：低氧暴露2h,24h后CRF分泌和皮质酮分泌被激活;低氧暴露5d后CRF分泌和皮质酮分泌活动减弱,并开始恢复;至低氧暴露15d后,这种分泌活动基本恢复,进入恢复期。     

中药合剂抗运动病作用与对血液内分泌激素水平的影响

目的:研究酸枣仁等十味中药组成的合剂对运动病的作用及对血液内分泌激素水平的影响。方法:根据Cramptom和Lucot报道,以绕水平轴的旋转刺激SD大鼠与毕格犬,观察大鼠异食高岭土行为、犬呕吐潜伏期,采用绕垂直轴的旋转刺激豚鼠,记录眼震电图,观察中药合剂对这些指标的影响。同时,用放射免疫法测定大鼠血浆精氨酸加压素(AVP)、皮质酮(Cort)、促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放激素(CRH)水平,观察经口给予中药合剂对这些内分泌指标的影响。结果:与旋转刺激对照组比较,中药合剂:①抑制大鼠异食高岭土行为(P<0.05),延长犬呕吐潜伏期(P<0.05),该作用呈一定的剂量依赖性;②减少豚鼠眼震频率和平均慢相速度(P<0.05);③抑制大鼠血浆Cort、ACTH、CRH、AVP水平的升高;④中药合剂的这些作用与阳性对照药茶苯海明类似。结论:①本实验所用中药合剂能有效抑制运动病;②中药合剂可抑制旋转刺激引起的血浆下丘脑-垂体-肾上腺皮质轴激素和AVP水平的升高。     

低氧暴露条件下高原鼠兔和大鼠HPA轴活动的比较

采用人工模拟低气压低氧的方法比较研究了不同程度（模拟海拔5 km和7 km)和不同时间（24d和5d）低氧暴露,对大鼠和高原鼠兔（Ochotona curzoniae）下丘脑-垂体-肾上腺皮质 (hypothalamo-pituitary-adrenalcortex,HPA)轴活动的影响。结果如下：7 km低氧暴露24 h,大鼠下丘脑的促肾上腺皮质激素释放激素（corticotropin-releasing actor,CRF）和肾上腺皮质激素皮质酮分泌显著增加,大鼠HPA低氧暴露对大鼠HPA 轴活动无显著差异。低氧暴露5天后,大鼠7 km、5 km组的HPA轴活动与对照相比无明显差异。低氧暴露对高原鼠兔的HPA轴无明显影响。上述结果表明：低氧暴露的时间和程度与大鼠HPA的活动密切相关;从HPA的活动来看,高原鼠兔表现出较强的低氧耐受性。     

淫羊藿总黄酮对肾阳虚大鼠下丘脑-垂体-肾上腺轴钙调蛋白基因表达的影响

目的:从分子水平探讨肾阳虚证病理改变及淫羊藿总黄酮的作用及其机理,为开发药物的临床新用途提供理论依据.方法:用大剂量外源糖皮质激素建立肾阳虚大鼠动物模型,以实时荧光定量RT-PCR技术,测定各组大鼠下丘脑-垂体-肾上腺轴CaM mRNA的表达,以及淫羊藿总黄酮对其的影响.结果:肾阳虚大鼠下丘脑、肾上腺CaMmRNA水平升高,垂体组织CaM mRNA水平没有显著变化,淫羊藿总黄酮能够降低下丘脑组织CaM mRNA水平,但对肾上腺影响不显著.结论:大鼠肾阳虚证时下丘脑中CaM mRNA水平升高,淫羊藿总黄酮可使其降低.     

通元针法对肝气郁结型卒中后抑郁患者血清神经营养因子和下丘脑-垂体-肾上腺素轴功能的影响

目的：观察通元针法对肝气郁结型卒中后抑郁（PSD）患者血清神经营养因子和下丘脑-垂体-肾上腺素轴功能的影响。方法：按照随机数字表法,将2021年9月-2022年11月期间佛山市中医院收治的PSD患者102例分为对照组（n=51,接受常规治疗）和观察组（n=51,对照组的基础上接受通元针法治疗）。对比两组疗效、抑郁情况、血清神经营养因子和下丘脑-垂体-肾上腺素轴功能指标的变化情况。结果：与对照组相比,观察组的临床总有效率更高（P<0.05）。与对照组治疗4周后、治疗8周后相比,观察组汉密尔顿抑郁量表24项版本（HAMD-24）评分更低（P<0.05）。与对照组治疗8周后相比,观察组血清神经生长因子（NGF）、脑源性神经营养因子（BDNF）、胰岛素样生长因子-1(IGF-1)更高,血浆促肾上腺皮质激素（ACTH）、皮质醇（Cor）、促肾上腺皮质激素释放激素（CRH）更低（P<0.05）。结论：肝气郁结型PSD患者采用通元针法治疗,抑郁症状可得到显著缓解,能够调节血清神经营养因子,改善下丘脑-垂体-肾上腺素轴功能,具有较高的应用价值。     

雌、雄大鼠去势对HPA轴分泌功能影响的比较

目的观察去势手术后雌、雄大鼠在低性激素状态下,下丘脑—垂体—肾上腺(HPA)轴功能的变化,证实性激素可对HPA轴的功能产生影响,并分析这种影响是否存在性别差异和时长效应。方法选用SPF级8周龄SD大鼠80只(雌雄各半),体重180~220 g,采用完全随机设计法,利用随机数字表将其分为雄性模型组、雄性对照组、雌性模型组、雌性对照组,每组20只大鼠,适应性饲养一周后行去势手术,于造模后第3周及第13周心脏取血,采用酶联免疫吸附法(ELISA)检测血清中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量并进行统计分析。结果经检测造模第3周雄性模型组大鼠血清CRH、CORT含量显著低于对照组(P0.01),血清ACTH含量低于对照组(P0.05);雌性模型组大鼠血清CRH、CORT含量均低于对照组(P0.05),血清ACTH含量有下降趋势。造模第13周,雄性模型组大鼠血清CORT含量显著低于对照组(P0.01),其他激素含量变化不明显;雌性模型组大鼠血清CORT含量低于对照组(P0.05),其他激素含量变化不明显。雌、雄模型组大鼠造模后第13周与第3周组内相比CRH、ACTH、CORT的含量均无统计学差异(P0.05)。结论无论雌、雄,去势均可造成大鼠HPA轴功能的紊乱,表现为外周血CRH、ACTH、CORT水平下降,雄激素对雄鼠HPA轴的影响要大于雌激素对雌鼠的影响。推测雄激素可能更加有利于上述三种激素的产生。当雌、雄大鼠处于稳定的低性激素状态,其HPA轴分泌功能不随着大鼠周龄的增长而发生改变。     

Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation

The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects. In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD. The effects of GHRH and CRH on sleep-endocrine activity during the recovery night after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between nights before and after 40 h of SD in 48 normal women and men aged 19-67 yr. During the recovery night, GHRH, CRH, or placebo were injected repetitively. After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with the baseline night. After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo. Also, after CRH, NREMS increased higher than after placebo, and a positive correlation was found between age and the baseline-related increase of slow-wave sleep. REMS increased after placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases in the lower frequencies and decreases in the higher frequencies during NREMS after each of the treatments. Cortisol and GH did not differ between baseline and recovery nights after placebo. After GHRH, GH increased and cortisol decreased. Cortisol increased after CRH. No sex differences were found in these changes. Our data suggest that GHRH and CRH augment NREMS promotion after SD. Marked differences appear to exist in peptidergic sleep regulation between spontaneous and recovery sleep.     

Growth hormone-releasing hormone facilitates hypoglycemia-induced release of cortisol

Early sleep in humans is characterized by a distinct suppression of pituitary-adrenal activity coinciding with enhanced activity of the somatotropic axis. Here, we tested in awake humans the hypothesis of an inhibiting influence of hypothalamic growth hormone-releasing hormone (GHRH) on pituitary-adrenal activity. For this purpose, pituitary-adrenal activity was stimulated in 10 men through a standard insulin-hypoglycemia-test (IHT) and in another 10 men through combined administration of CRH/vasopressin. Stimulation was performed in each man on three conditions following pretreatment with Placebo and GHRH administered intravenously (50 microg) or intranasally (300 microg) 1 h before. GH, ACTH and cortisol as well as blood pressure and heart rate were measured repeatedly. Contrary to expectations, pretreatment with GHRH did not suppress but enhanced secretion of cortisol upon insulin-induced hypoglycemia regardless of the route of GHRH pretreatment (p<0.05). In contrast, GHRH did not facilitate cortisol release after stimulation with CRH/vasopressin. Changes in ACTH remained inconsistent. Plasma levels of GH increased significantly after i.v. GHRH application, but remained unchanged after the intranasal administration. Blood pressure and heart rate were not influenced by the treatments. Results indicate facilitating effects of GHRH mediated at a suprapituitary (i.e. hypothalamic) level as suggested by restriction of the effect to the hypoglycemia-induced cortisol release with no effects after pituitary stimulation with CRH/vasopressin.     

间断低氧对大鼠下丘脑超微结构及前增食欲素水平的影响

目的探讨睡眠中间断低氧对大鼠下丘脑前增食欲素及受体水平的影响以及下丘脑超微结构的变化。方法大鼠分成对照组、间断低氧组和持续低氧组,分别给予吸入空气,持续低氧和间断低氧气体,并在实验开始后1d、3d、1w和4w应用RT-PCR方法测定大鼠下丘脑前增食欲素及受体水平,分析其间的变化关系,电镜观察下丘脑的超微结构变化。结果与对照组和持续低氧组比较,间断低氧4w后大鼠下丘脑前增食欲素mRNA水平明显降低,受体水平升高,但在持续低氧和对照组之间无明显差异。在低氧后1d、3d、7d后大鼠下丘脑前增食欲素mRNA降低,受体水平升高,在4w后,持续低氧组则接近正常。急性持续低氧大鼠超微结构变化更严重,而慢性间断低氧变化更持久。结论慢性间断低氧可以引起下丘脑前增食欲素下降及受体水平升高,急性持续低氧也可引起上述变化,而慢性持续低氧未引起增食欲素改变;慢性间断低氧大鼠下丘脑超微结构表现为严重而持久的变化。     

Effects of cortisol treatment on brain and adrenal corticotropin-releasing hormone (CRH) content and other parameters regulated by CRH

Corticotropin-releasing hormone (CRH) has been found in both hypothalamic and extrahypothalamic sites of the brain and also in the adrenal medulla. To study the timing and location of delayed glucocorticoid action in rats, we measured the effects of 2-day and 7-day cortisol treatment on immunoreactive CRH concentrations in hypothalamus, cerebral cortex, hippocampus, cerebellum, and adrenal gland. The activity of the hypothalamo-pituitary-adrenal (HPA) axis and the sympathoadrenal system were also measured. Studies were carried out both in the afternoon and/or in the morning, to get information about possible circadian changes. CRH contents were not changed in any brain areas studied, except there was a trend of decrease in the hypothalamus compared to vehicle in the afternoon due to the lack of circadian increase after 7-day cortisol treatment. Pituitary ACTH content decreased significantly after 7-day treatment, while beta-endorphin did not. Plasma levels of ACTH, corticosterone, norepinephrine and epinephrine and adrenal ACTH and beta-endorphin contents decreased after 2-day, adrenal CRH content after 7-day treatment with cortisol. Our findings suggest, that chronic cortisol treatment inhibits the circadian activation of the HPA axis at all levels but has variable effects on baseline measures because it causes different changes in release and synthesis at different sites.     

Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

Glucocorticoids are essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity; however, recent studies warn that exposure to excess endogenous or synthetic glucocorticoid during a specific period of prenatal development adversely affects HPA axis stability. We administered dexamethasone (DEX) to pregnant rats during the last week of gestation and investigated subsequent HPA axis regulation in adult male offspring in unrestrained and restraint-stressed conditions. With the use of real-time PCR and RIA, we examined the expression of regulatory genes in the hippocampus, hypothalamus, and pituitary, including corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoid receptors (GR), mineralcorticoid receptors (MR), and 11-beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1), as well as the main HPA axis hormones, adrenal corticotropic hormone (ACTH) and corticosterone (CORT). Our results demonstrate that the DEX-exposed group exhibited an overall change in the pattern of gene expression and hormone levels in the unrestrained animals. These changes included an upregulation of CRH in the hypothalamus, a downregulation of MR with a concomitant upregulation of 11beta-HSD-1 in the hippocampus, and an increase in circulating levels of both ACTH and CORT relative to unrestrained control animals. Interestingly, both DEX-exposed and control rats exhibited an increase in pituitary GR mRNA levels following a 1-h recovery from restraint stress; however, the increased expression in DEX-exposed rats was significantly less and was associated with a slower return to baseline CORT compared with controls. In addition, circulating levels of ACTH and CORT as well as hypothalamic CRH and hippocampal 11beta-HSD-1 expression levels were significantly higher in the DEX-exposed group compared with controls following restraint stress. Taken together, these data demonstrate that late-gestation DEX exposure in rats is associated with persistent changes in both the modulation of HPA axis activity and the HPA axis-mediated response to stress.     

Ovine corticotropin-releasing hormone stimulation test in patients with chronic renal failure: pharmacokinetic properties, and plasma adrenocorticotropic hormone and serum cortisol responses

The data on the status of the hypothalamic-pituitary-adrenal (HPA) axis in haemodialysis (HD) patients are conflicting. Moreover, a state reminiscent of Cushing's syndrome has been reported in this group of patients. Corticotropin-releasing hormone (CRH), that is produced by the hypothalamus and modulates the secretion of adrenocorticotropic hormone (ACTH), has been shown to be useful as a provocative test of the HPA axis. We investigated the effect of exogenous ovine CRH (oCRH) on plasma levels of ACTH and cortisol in 13 chronic HD patients. The plasma concentrations of immunoreactive CRH following oCRH administration were similar in patients and controls. In all patients, oCRH given intravenously as bolus injection caused a further increase in the already elevated levels of cortisol. The mean basal plasma levels of ACTH were within the normal range. There was, however, a blunted ACTH response to oCRH. We conclude that the HPA axis in chronic HD patients retains the ability to respond to exogenous oCRH. The patterns of the ACTH and cortisol response to this peptide resemble those observed in chronic stress (depression, anorexia nervosa). Besides, the kinetics of disappearance of oCRH indicate that the kidney may not be the major organ that metabolizes oCRH.     

HPA-axis responses during experimental colitis in the rat

We investigated the responses of the hypothalamic-pituitary-adrenal (HPA) axis during experimental colitis induced by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid in the rat. On days 3 and 7 after induction of colitis, the corticotropin-releasing hormone (CRH) mRNA level in the parvocellular paraventricular nucleus (pPVN) of the hypothalamus was reduced, the plasma ACTH level remained at the basal level, and the plasma corticosterone (Cort) level was high. Induction of colitis on day 3 after adrenalectomy with Cort pellet replacement (ADX + Cort) resulted in a marked increase in CRH mRNA on day 7 after induction of colitis compared with noncolitic ADX + Cort animals. Pair feeding to match the food intake of the colitic animals resulted in no significant change in CRH mRNA in the pPVN, plasma ACTH, and Cort compared with healthy control animals. These findings indicated that CRH mRNA expression in the pPVN was inhibited by glucocorticoid feedback during this experimental colitis, and the decrease in food intake during colitis was not simply responsible for the expression of CRH mRNA. It is inferred that the HPA axis including the CRH level in the pPVN is altered in patients with inflammatory bowel disease.     

Ghrelin is released from rat hypothalamic explants and stimulates corticotrophin-releasing hormone and arginine-vasopressin.

Ghrelin and synthetic growth hormone secretagogues have diverse effects on the hypothalamus including effects on appetite and the growth hormone axis as well as on the hypothalamus-pituitary-adrenal (HPA) axis. We previously studied the effect of synthetic growth hormone secretagogues on CRH and AVP release from rat hypothalami in vitro, and now report on the effects of ghrelin on CRH and AVP release. The ghrelin protein content and ghrelin output from rat hypothalamic explants was measured using a specific novel ghrelin enzyme immunoassay. The effect of 10(-8) M to 10(-6) M ghrelin on CRH and AVP release was studied in the rat hypothalamic explants, where stimulation with des-octanoyl ghrelin was used as control. The presence of both ghrelin mRNA and protein could be shown in the rat hypothalamus. Ghrelin output was detected in the incubation fluid of rat hypothalamic explants and could be stimulated with high potassium concentrations. Our data also demonstrated a dose-dependent effect of ghrelin on both CRH and AVP release, while des-octanoylated ghrelin showed no effect on either peptide. In summary, the current data suggest that ghrelin is expressed in the hypothalamus both at RNA and the protein levels. Ghrelin stimulates the HPA axis in the rat via stimulation of both CRH, and particularly, AVP release from the hypothalamus. The local autocrine/paracrine and endocrine effects of ghrelin in the hypothalamus could influence all the hormonal systems involved in ghrelin effects, including growth hormone release, the HPA axis and appetite.