BACKGROUND & AIMS: :Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis.

背景与目标： ：血管生成是包括肿瘤生长和转移在内的许多病理学中至关重要的一步。在这里，我们表明倾斜的肽发挥抗血管生成活性。倾斜（或倾斜定向）的肽是已知的使膜和脂质核心不稳定的短肽，其特征是当螺旋状时，疏水性残基沿轴不对称分布。我们以前已经表明，人类催乳激素/生长激素（PRL / GH）家族成员的16 kDa片段是有效的血管生成抑制剂。在这里，我们证明所有这些片段均具有具有倾斜肽特征的14-aa序列。人催乳激素和人生长激素的倾斜肽在体外和体内均可诱导内皮细胞凋亡，抑制内皮细胞增殖和抑制毛细血管形成。当肽的疏水性梯度因突变而改变时，这些抗血管生成作用被消除。我们进一步证明了猿猴免疫缺陷病毒gp32和阿尔茨海默氏β-淀粉样蛋白肽的众所周知的倾斜肽也是血管生成抑制剂。综上所述，这些结果表明倾斜的肽在调节血管生成中具有潜在的新作用。

BACKGROUND & AIMS: :Thyroid hormone (TH) regulates such crucial biological functions as normal growth, development and metabolism of nearly all vertebrate tissues. In skeletal muscle, TH plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells. Regulation of the expression and activity of the deiodinases constitutes a cell-autonomous, pre-receptor mechanism that controls crucial steps during the various phases of myogenesis. Here, we review the roles of deiodinases in skeletal muscle stem cells, particularly in muscle homeostasis and upon regeneration. We focus on the role of T3 in stem cell functions and in commitment towards lineage progression. We also discuss how deiodinases might be therapeutically exploited to improve satellite-cell-mediated muscle repair in skeletal muscle disorders or injury.

背景与目标： 甲状腺激素（TH）调节着至关重要的生物学功能，例如几乎所有脊椎动物组织的正常生长，发育和代谢。在骨骼肌中，TH在调节卫星细胞（真正的骨骼肌干细胞）的功能中起着至关重要的作用。已发现脱碘酶（D2和D3）可调节卫星细胞中各种TH靶基因的表达。脱碘酶的表达和活性的调节构成了细胞自主的前受体机制，该机制在肌生成的各个阶段中控制关键步骤。在这里，我们回顾了脱碘酶在骨骼肌干细胞中的作用，特别是在肌肉稳态和再生中。我们专注于T3在干细胞功能中的作用以及对谱系进展的承诺。我们还将讨论如何在骨骼肌疾病或损伤中治疗性利用脱碘酶来改善卫星细胞介导的肌肉修复。

BACKGROUND & AIMS: PURPOSE:The incidence of poor ovarian response in controlled ovarian stimulation (COH) has been reported in 9-24 % of IVF-ET cycles. Growth hormone augments the effect of gonadotropin on granulosa and theca cells, and plays an essential role in ovarian function, including follicular development, estrogen synthesis and oocyte maturation. The aim of this study was to assess IVF-ET cycle outcome after the addition of growth hormone in antagonist protocol in poor responders. MATERIALS AND METHODS:Eighty-two poor responder patients selected for ART enrolled the study and were randomly divided into two groups. Group I (GH/HMG/GnRHant group, n = 40) received growth hormone/gonadotropin/GnRH antagonist protocol and group II (HMG/GnRHant group, n = 42) received gonadotropin/GnRH antagonist protocol. RESULTS:The number of retrieved oocytes was significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 6.10 ± 2.90 vs. 4.80 ± 2.40 (p = 0.035) and the number of obtained embryos was also significantly higher in GH/HMG/GnRHant group than HMG/GnRHant group, 3.7 ± 2.89 as compared to 2.7 ± 1.29 (p = 0.018). There were no significant differences between groups regarding implantation, and chemical and clinical pregnancy rates. CONCLUSION:Our study showed that co-treatment with growth hormone in antagonist protocol in patients with a history of poor response in previous IVF-ET cycles did not increase pregnancy rates.

背景与目标： 目的：在IVF-ET周期的9-24％中，有报道称在受控卵巢刺激（COH）中卵巢反应不良的发生率。生长激素增强了促性腺激素对颗粒和卵泡膜细胞的作用，并且在卵巢功能（包括卵泡发育，雌激素合成和卵母细胞成熟）中起着至关重要的作用。这项研究的目的是评估在不良反应者的拮抗剂方案中添加生长激素后的IVF-ET周期结果。
材料与方法：选择接受抗逆转录病毒治疗的82位反应较差的患者作为研究对象，并将其随机分为两组。第一组（GH / HMG / GnRHant组，n = 40）接受生长激素/促性腺激素/ GnRH拮抗剂方案，而第二组（HMG / GnRHant组，n = 42）接受促性腺激素/ GnRH拮抗剂方案。
结果：GH / HMG / GnRHant组的回收卵母细胞数量显着高于HMG / GnRHant组，分别为6.10±2.90和4.80±2.40（p = 0.035），并且GH / HMG中获得的胚胎数量也明显更高/ GnRHant组比HMG / GnRHant组为3.7±2.89，而2.7±1.29（p = 0.018）。两组之间在植入，化学和临床妊娠率方面无显着差异。
结论：我们的研究表明，在先前的IVF-ET周期中有不良反应史的患者中，在拮抗剂方案中与生长激素共同治疗不会增加妊娠率。

BACKGROUND & AIMS: OBJECTIVE:Anticipated pain with intrauterine device (IUD) insertion may be a barrier to widespread use. Our objective was to evaluate the efficacy of intracervical 2% lidocaine gel for pain relief with IUD insertion. STUDY DESIGN:We performed a double-blind, randomized controlled trial of women undergoing IUD insertion. Participants were randomly assigned to 2% lidocaine or placebo gel. Study gel (3 mL) was placed 3 minutes prior to IUD insertion. Pain scores were measured at various time points using a 10-point visual analog scale. RESULTS:Of the 200 participants randomized, 199 completed the study. Pain scores among lidocaine and placebo arms were similar at tenaculum placement (lidocaine and placebo: median, 4; range, 0-10; P = .15) and with insertion (lidocaine: median, 5; range, 1-10; placebo: median, 6; range, 0-10; P = .16). These results did not differ by parity. CONCLUSION:Topical or intracervical 2% lidocaine gel prior to IUD insertion does not decrease pain scores.

背景与目标： 目的：宫内节育器（IUD）插入会导致预期的疼痛可能是广泛使用的障碍。我们的目标是评估2％利多卡因腹腔内凝胶治疗宫内节育器疼痛缓解的效果。
研究设计：我们对接受宫内节育器植入的妇女进行了一项双盲，随机对照试验。参与者被随机分配到2％利多卡因或安慰剂凝胶中。在插入宫内节育器之前3分钟放置研究凝胶（3 mL）。使用10点视觉模拟量表在各个时间点测量疼痛评分。
结果：在随机分配的200名参与者中，有199名完成了研究。利多卡因和安慰剂组之间的疼痛评分在触角放置（利多卡因和安慰剂：中位数，4；范围，0-10； P = .15）和插入时（利多卡因：中位数，5；范围，1-10；安慰剂：中位数为6；范围为0-10； P = 0.16）。这些结果在均等方面没有差异。
结论：在宫内节育器插入前局部或颅内使用2％利多卡因凝胶不会降低疼痛评分。

BACKGROUND & AIMS: This article describes the use and prescribing of menopausal and postmenopausal hormone therapy (HT) in one example country, Finland, and the trends and levels of HT use in other western countries for comparison. Previously published studies were reviewed and reanalyzed, and some additional unpublished data from Finnish surveys were compiled. The use of HT increased in Finland up to 1994. In Finland the initiative for HT use came more often from physicians than women themselves, physicians valued HT more than women, women's period of use of HT was shorter than physicians' recommendations, women's reasons for using HT were usually to treat symptoms, but physicians considered HT also useful in the prevention of later diseases. Gynecologists were more favorable toward HT than other physicians. HT has become common in very different times in different countries, but with the exception of the US experience in the 1970s, the trend has been towards increasing use. One motivation to do surveys on physicians' prescribing or women's use of HT has been to facilitate HT use. The large variation in HT use may reflect the uncertainty concerning its true value. The reasons for the large-scale prevention with HT have not been systematically studied, but it is likely due to various social and commercial forces.

背景与目标： 本文介绍了一个示例国家芬兰的绝经和绝经后激素治疗（HT）的使用和处方，并比较了其他西方国家使用HT的趋势和水平，以进行比较。审查并重新分析了以前发表的研究，并汇编了芬兰调查中的一些其他未发表的数据。直到1994年，芬兰对HT的使用有所增加。在芬兰，使用HT的倡议更多地是来自医生而不是女性本身，医生对HT的重视程度高于女性，女性使用HT的时间短于医师的建议，这是妇女的原因。通常使用HT来治疗症状，但医生认为HT还可用于预防以后的疾病。妇科医生比其他医生更倾向于HT。 HT在不同国家的不同时代已经很普遍，但是除了美国在1970年代的经验外，趋势是越来越多地使用它。对医生的处方或女性使用HT进行调查的动机之一是促进HT的使用。 HT使用量的巨大差异可能反映了其真实价值的不确定性。大规模预防HT的原因尚未得到系统的研究，但这可能是由于各种社会和商业力量造成的。

BACKGROUND & AIMS: :The level of cyclic AMP in various fractions of rat skeletal tissue was measured after in vitro or in vivo administration of parathyroid hormone and calcitonin. Incubations of bone fractions prepared from young (5 weeks of age thyroparathyroidectomized rats revealed that both parathyroid hormone and calcitonin increased the cyclic AMP level in fractions of epiphysis, metaphysis and marrow cells. Cyclic AMP accumulation in incubated perisoteum and diaphysis were induced solely by parathyroid hormone. In in vivo experiments the cyclic AMP level in the tibia of the thyroparathyroidectomized rat was increased by infusion of either parathyroid hormone or calcitonin, and the simultaneous administration of each maximally effective dose of the two hormones exhibited an additive effect. Within 2 min, parathyroid hormone infusion caused an elevation of cyclic AMP content in periosteum and metaphysis. Rapid increase of cyclic AMP in the metaphysis was also induced by calcitonin, and the effect of the two hormones on cyclic AMP accumulation in this fraction was additive. Small but significant increase of cyclic AMP in the diaphysis was detected at 5 min after the administration of parathyroid hormone. Calcitonin infusion did not show any consistent effects on periosteum and diaphysis.

背景与目标： ：在体外或体内给予甲状旁腺激素和降钙素后，测量大鼠骨骼组织各部分中环AMP的水平。从年轻（5周龄甲状腺副甲状腺切除的大鼠）制备的骨级分的培养表明，甲状旁腺激素和降钙素均会增加骨epi，干physi端和骨髓细胞部分中的环AMP含量。仅在甲状旁腺激素的诱导下，骨膜和骨干中的循环AMP积累是诱因。在体内实验中，通过注射甲状旁腺激素或降钙素可增加甲状旁腺切除大鼠的胫骨中的环AMP含量，同时最大剂量的两种激素同时给药显示出加和作用，在2分钟内，甲状旁腺激素注入引起骨膜和干meta端的环AMP含量升高，降钙素还引起干physi端的环AMP迅速增加，这两种激素对该部分中环AMP的积累具有累加作用。在5 min时检测到骨干中的环状AMP服用甲状旁腺激素后。降钙素输注对骨膜和骨干没有显示出任何一致的影响。

BACKGROUND & AIMS: PURPOSE:Steroid sulfatase (STS) inhibitors that can decrease or prevent the biosynthesis of estrogenic steroids via the sulfatase route may play an important role in the treatment of breast cancer. We compare the in vivo efficacy of two potent STS inhibitors, STX64 and STX213, in a xenograft breast cancer model. EXPERIMENTAL DESIGN:MCF-7 cells stably expressing STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of estradiol sulfate (E2S) and bearing both MCF-7STS and wild-type MCF-7 (MCF-7WT) tumors were orally treated with STX64 and STX213. Treatment was given for 49 days followed by a recovery period of 35 days in which animals received only E2S. Mice were weighed, and tumor measurements were taken weekly. RESULTS:STX64 and STX213 exhibited potent STS inhibition in vivo. However, STX213 showed a greater duration of activity. In vehicle-treated nude mice receiving E2S, tumor volumes increased 5.5-fold for MCF-7WT and 3.8-fold for MCF-7STS after 49 days compared with day 0. MCF-7WT tumor growth was reduced by 56% by STX213 over the dosing period, and subsequent growth was retarded during the recovery period. All treatments fully inhibited growth of MCF-7STS tumors, and recovery of these tumors was significantly retarded (P<0.01). All compounds completely inhibited liver and tumor STS activity. Additionally, STS mRNA expression in the MCF-7STS tumors directly correlated with the corresponding STS enzyme activity. CONCLUSIONS:This study indicates that STS inhibitors attenuate hormone-dependent human breast cancer growth and therefore offer a potentially novel treatment for this condition.

背景与目标： 用途：类固醇硫酸酯酶（STS）抑制剂可通过硫酸酯酶途径减少或阻止雌激素类固醇的生物合成，可能在乳腺癌的治疗中起重要作用。我们比较了两种有效的STS抑制剂STX64和STX213在异种移植乳腺癌模型中的体内疗效。
实验设计：产生稳定表达STS cDNA（MCF-7STS）的MCF-7细胞。接受皮下切除的卵巢切除的MF-1雌性裸鼠注射雌二醇硫酸盐（E2S）并同时携带MCF-7STS和野生型MCF-7（MCF-7WT）肿瘤的患者，应使用STX64和STX213口服治疗。给予49天的治疗，然后恢复35天，其中动物仅接受E2S。称重小鼠，每周进行一次肿瘤测量。
结果：STX64和STX213在体内表现出有效的STS抑制作用。但是，STX213显示了更长的活动时间。在接受E2S的媒介物治疗的裸鼠中，与第0天相比，在49天后，MCF-7WT的肿瘤体积增加了5.5倍，MCF-7STS的肿瘤体积增加了3.8倍。STX213使MCF-7WT的肿瘤生长比给药减少了56％期间，随后的生长在恢复期受到阻碍。所有治疗均完全抑制MCF-7STS肿瘤的生长，并且这些肿瘤的恢复显着受阻（P <0.01）。所有化合物均完全抑制肝脏和肿瘤STS活性。此外，MCF-7STS肿瘤中的STS mRNA表达与相应的STS酶活性直接相关。
结论：这项研究表明，STS抑制剂可减弱激素依赖性人类乳腺癌的生长，因此可为这种情况提供潜在的新颖治疗方法。

BACKGROUND & AIMS: :The serum concentrations of a specific GH-binding protein, derived from the GH receptor, were assayed in sera from 62 African pygmies and 101 normal statured controls. Samples were assayed in the absence and presence of excess GH using 2 separatory procedures. Interassay variability for samples was corrected by a standard reference pool of sera from adults assayed with all unknown samples. Results were expressed as specific binding relative to this standard. The mean percent relative specific binding for GH increased with age in normal-statured controls throughout childhood and adolescence. Relative specific binding for GH was 37.0 +/- 2.0% (mean +/- SEM) in control subjects between the ages of 1-5 yr (mean age, 2.9 yr) and increased progressively to 93.0 +/- 7.0% in young adults (mean age, 23 yr). The relative specific binding of GH by serum from pygmies did not exceed 30.1 +/- 3.4% of the control adult standard at any age period (P less than 0.001), and there was no progressive age-related increase in binding. The decrease from normal binding was minimal in pygmies during childhood (29%), but the decrease from normal was 60-70% in adolescents and adults. Thus, short stature in pygmies probably results not from an absolute deficiency of GH receptors per se, as in Laron dwarfism, but from a failure of cellular GH receptors to increase in a normal manner. This is most compatible with a change in regulating expression of the GH receptor gene, rather than a structural defect in the coding sequence of the GH receptor gene.

背景与目标： ：在来自62个非洲py鼠和101个正常对照的血清中测定了从GH受体衍生的特定GH结合蛋白的血清浓度。使用2种分离方法在不存在和存在过量GH的情况下分析样品。通过使用所有未知样品进行分析的成人血清标准参比库对样品的测定间变异性进行了校正。结果表示为相对于该标准的特异性结合。在整个童年和青春期，正常控制的对照组中GH的平均相对特异性结合百分比随年龄增加而增加。在1-5岁（平均年龄为2.9岁）之间的对照受试者中，GH的相对特异性结合为37.0 /-2.0％（平均水平/-SEM），而在年轻人（平均年龄）中逐渐增加至93.0 /-7.0％ ，23年）。在任何年龄段，侏儒血清中GH的相对特异性结合率均不超过对照成人标准的30.1 /-3.4％（P小于0.001），并且没有与年龄相关的进行性结合增加。在侏儒时期，正常binding缩的减少极少（29％），但在青少年和成人中，normal缩比正常的减少为60-70％。因此，侏儒矮小可能不是由于GH受体本身的绝对缺乏（如Laron侏儒症），而是由于细胞GH受体不能以正常方式增加。这与调节GH受体基因表达的变化最相容，而不是与GH受体基因编码序列的结构缺陷最相容。

BACKGROUND & AIMS: BACKGROUND:The majority of patients receive HT after biochemical progression despite primary therapy of prostate cancer with curative intent. It is difficult to differentiate at a low rise in PSA level, e.g.,

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Some peptide hormones are associated with specific, high-affinity plasma proteins. The major binding protein (BP) for growth hormone (GH) in humans is a circulating fragment of the GH membrane receptor, consisting of the hydrophilic, extracellular portion of that transmembrane glycoprotein. The circulating levels of GH-BP mirror the levels of GH receptors. There are 4 well-characterized insulin-like growth factor (IGF)-BPs. One IGF-binding component in plasma is a fragment of the extracellular portion of the IGF-II/mannose-6-phosphate receptor, analogous to the GH-BP. The 3 other cloned IGF-BPs form a homologous family of proteins with differences in structure, glycosylation and hormonal control that suggest differences in function. The GH- and IGF-BPs play a major role in the metabolism and biological action of these peptide hormones.

背景与目标： ：某些肽激素与特定的高亲和力血浆蛋白有关。人类生长激素（GH）的主要结合蛋白（BP）是GH膜受体的循环片段，由该跨膜糖蛋白的亲水性细胞外部分组成。 GH-BP的循环水平反映了GH受体的水平。有4个特征明确的胰岛素样生长因子（IGF）-BP。血浆中的一种IGF结合成分是IGF-II /甘露糖6-磷酸受体的胞外部分的片段，类似于GH-BP。其他3个克隆的IGF-BPs形成同源的蛋白质家族，其结构，糖基化和激素控制方面存在差异，提示其功能存在差异。 GH-和IGF-BP在这些肽激素的代谢和生物学作用中起主要作用。

BACKGROUND & AIMS: :Growth hormone (GH) is a major regulator of growth, somatic development and body composition. Sex steroids can act centrally by regulating GH secretion and peripherally modulating GH responsiveness. This review addresses data of potential clinical relevance on how sex steroids modulate GH secretion and action, aiming to increase the understanding of sex steroid/GH interactions and leading to improved management of patients. Sex steroids regulate GH secretion directly as well as indirectly through IGF-I modulation. Testosterone stimulates GH secretion centrally, an effect dependent on prior aromatization to oestrogen. Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback inhibition. Whether oestrogen stimulates GH secretion centrally in females is unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and protein anabolism while exhibiting similar but independent actions of its own. Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of the liver. This is a concentration-dependent phenomenon that arises invariably from oral administration of therapeutic doses of oestrogen, an effect that can be avoided by using a parenteral route. This strong modulatory effect of gonadal steroids on GH responsiveness provides insights into the biological basis of sexual dimorphism in growth, development and body composition and practical information for the clinical endocrinologist. It calls for an appraisal of the diagnostic criteria for GH deficiency of GH stimulation tests, which currently are based on arbitrary cut-offs that do not take into account the shifting baseline from the changing gonadal steroid milieu. In the management of GH deficiency in the hypopituitary female, oestrogen should be administered by a nonoral route. In hypopituitary men, androgens should be replaced concurrently to maximize the benefits of GH. In the general population, the metabolic consequences of long-term treatment of women with oral oestrogen compounds, including selective oestrogen receptor modulators, are largely unknown and warrant study.

背景与目标： ：生长激素（GH）是生长，体细胞发育和身体成分的主要调节剂。性类固醇可以通过调节GH分泌并在外围调节GH反应性来发挥中心作用。这篇综述探讨了有关性类固醇如何调节GH分泌和作用的潜在临床相关性数据，旨在增进对性类固醇/ GH相互作用的了解并改善患者的管理。性类固醇直接或通过IGF-I调节间接调节GH的分泌。睾丸激素可集中刺激GH分泌，其作用取决于先前对雌激素的芳香化作用。雌激素通过减少IGF-1反馈抑制作用间接刺激GH分泌。雌激素是否能集中刺激女性的GH分泌尚无定论。性腺类固醇会改变GH的代谢作用。睾丸激素可放大IGF-1的GH刺激，钠保留，底物代谢和蛋白质合成代谢，同时表现出类似但独立的作用。雌激素通过抑制GH调节的肝脏内分泌功能来减弱GH的作用。这是一种浓度依赖性现象，总是由口服治疗剂量的雌激素引起，这种现象可以通过肠胃外途径避免。性腺类固醇对GH反应性的这种强调节作用，为临床内分泌学家提供了生长，发育和身体组成方面性二态性的生物学基础的见解，并为临床提供了实用信息。它要求对GH刺激试验中GH缺乏的诊断标准进行评估，该诊断标准目前基于任意临界值，该临界值未考虑来自不断变化的性腺类固醇环境的基线变化。在垂体下垂体GH缺乏症的治疗中，应通过非口服途径给予雌激素。在垂体下垂的男性中，应同时更换雄激素以最大程度地增加GH的益处。在一般人群中，口服雌激素化合物（包括选择性雌激素受体调节剂）对妇女进行长期治疗的代谢后果在很大程度上尚不清楚，值得研究。

BACKGROUND & AIMS: :The size of the pool of growing follicles was normal after prolonged down-regulation, as indicated by normal AMH levels 4 and 8 weeks after goserelin administration. However, there was a profound down-regulation of LH levels; therefore we suggest administration of exogenous LH to proceed to IVF or alternatively stimulation of endogenous LH secretion with daily administration of GnRH agonist. These need to be assessed prospectively.

背景与目标： ：在长期下调后，生长的卵泡池大小正常，这是在给予戈舍瑞林后4和8周正常的AMH水平所表明的。但是，LH水平有明显的下调。因此，我们建议每天给予GnRH激动剂来给予外源性LH进行IVF或刺激内源性LH分泌。这些需要进行前瞻性评估。

BACKGROUND & AIMS: :Rats treated neonatally or at four weeks of age with dexamethasone on a single occasion showed a considerable decrease in thymic glucocorticoid reception. It appears that hormonal imprinting can take place in the cells of the cytogenic organs not only perinatally, but also later, owing to the undifferentiated (differentiating) state of the forming cells.

背景与目标： ：单次用地塞米松治疗新生儿或四周大的鼠，胸腺糖皮质激素的接受量显着下降。似乎由于形成细胞的未分化（分化）状态，激素印记不仅可以在围产期发生在细胞发生器官的细胞中，而且以后也可以发生。

BACKGROUND & AIMS: OBJECTIVE:The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. MATERIALS AND METHODS:Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. RESULTS:The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. CONCLUSIONS:The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

背景与目标： 目的：采用酶法，组织学和免疫组化技术研究褪黑激素对松果体切除大鼠的抗氧化状态的影响。这项研究的目的是研究褪黑激素对海马细胞凋亡的影响。
材料与方法：雄性Wistar大鼠（n = 21）分为3组：将I组和II组分别作为对照组（假松果体切除术）和松果体切除的大鼠。从手术后第7天开始，对第三组的大鼠进行松果体切除术，并每天注射褪黑激素（1 mg / kg），持续3个月。在实验期结束时，所有大鼠被斩首处死。取出大鼠的大脑，并从所有脑标本中获得海马组织。所有大鼠的右海马标本用于测定超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）水平。所有动物的左海马组织标本用于免疫组织化学和组织学评估。
结果：与对照组相比，松果体切除的大鼠的SOD和GSH-Px水平显着降低，MDA水平显着升高。在该组的组织学和免疫组织化学评价中，观察到了泌尿生殖细胞的增加，液泡变性和细胞凋亡。然而，在松果体切除术后施用褪黑激素的大鼠中检测到SOD和GSH-Px酶活性增加，而MDA水平降低。此外，褪黑素治疗的大鼠失去了由松果体切除术引起的海马组织学和凋亡的改变。
结论：我们的研究结果表明，褪黑素能抑制松果体切除术引起的海马组织氧化损伤和形态变化。