BACKGROUND & AIMS: :The purpose of this study was to compare differences of the psychological burdens between young male transsexuals and age-gender matched non-transsexuals with standardized psychiatric rating scales in Korea. A total of 43 biologically unrelated young male transsexuals and 49 age-gender matched non-transsexuals participated in the study. All subjects completed Beck's Depression Inventory (BDI), Social Avoidance and Distress Scale (SADS), Self-Esteem Scale (SES) and Family Adaptability and Cohesion Evaluation Scale (FACES-III). The transsexuals showed significantly higher scores on the BDI (P < 0.0001) and SADS (P = 0.002) and lower scores on the SES (P < 0.0001) and Adaptability and Cohesion subscales (P = 0.016 and P < 0.0001, respectively) of the FACES-III than those of the non-transsexuals. The present study found young male transsexuals may be potentially vulnerable to develop psychiatric and familial problems in comparison with non-transsexuals, at least in Korea, although methodological limitations exist. Further well-designed researches should be launched to confirm this preliminary study.

背景与目标： : 这项研究的目的是比较韩国年轻男性变性人与年龄与性别相匹配的非变性人之间的心理负担差异，并采用标准化的精神病评定量表。共有43名与生物学无关的年轻男性变性者和49名年龄性别匹配的非变性者参加了这项研究。所有受试者均完成贝克抑郁量表 (BDI) 、社会回避与困扰量表 (SADS) 、自尊量表 (SES) 和家庭适应性与凝聚力评价量表 (FACES-III)。变性者在BDI (P < 0.0001) 和SADS (P = 0.002) 上的得分明显较高，在SES (P < 0.0001) 和适应性和凝聚力分量表上的得分较低 (P = 0.016和P <0.0001)，分别) 的脸-III比非变性人的脸。本研究发现，与非变性者相比，年轻的男性变性者可能容易出现精神和家庭问题，至少在韩国是这样，尽管方法上存在局限性。应开展进一步精心设计的研究，以确认这一初步研究。

BACKGROUND & AIMS: :Gender dysphoria is a condition in which a discrepancy between biological sex and gender identity causes distress. Many female-to-male transsexuals (FTMTS) are uncomfortable with female breasts. Chest wall contouring surgery is effective for obtaining a male-type chest, reducing mental stress, and increasing sexual satisfaction in such cases. At the Okayama University Hospital Gender Center, we have obtained positive results using an algorithm to determine the most appropriate surgical method for chest wall contouring in FTMTS patients. However, serious complications requiring reoperation, such as hematoma, may still occur. Postoperative hematomas were found in 15 (4.18%) of 358 FTMTS patients who underwent chest contouring surgery at our hospital between 2006 and 2018. Postoperative hematoma was examined retrospectively. The median time to the onset of hematoma was 7 (6-12) h after the initial surgery. The main blood vessels causing bleeding were those in the head-side skin flap region where visual confirmation was difficult and the perforator vessels from the pectoralis major muscle. Intraoperative bleeding and the operation time had a significant impact on the onset of postoperative hematoma. This is the first retrospective study that investigated the blood vessels and other factors contributing to postoperative hematoma development after chest wall contouring.

背景与目标： : 性别不安是生物性别和性别认同之间的差异导致困扰的一种情况。许多女性变性人 (FTMTS) 对女性乳房不舒服。在这种情况下，胸壁轮廓手术可有效获得男性型胸部，减轻精神压力并提高性满意度。在冈山大学医院性别中心，我们使用一种算法来确定最适合FTMTS患者胸壁轮廓的手术方法，从而获得了积极的结果。但是，仍然可能发生需要再次手术的严重并发症，例如血肿。在我们医院2006年和2018年接受胸部整形手术的358例FTMTS患者中，有15例 (4.18% 例) 发现了术后血肿。回顾性检查术后血肿。初次手术后至血肿发作的中位时间为7 (6-12) 小时。引起出血的主要血管是难以进行视觉确认的头侧皮瓣区域和胸大肌的穿支血管。术中出血和手术时间对术后血肿的发生有显著影响。这是第一个回顾性研究，研究了胸壁轮廓后导致术后血肿发展的血管和其他因素。

BACKGROUND & AIMS: :Prenatal exposure to androgens has been implicated in transsexualism but the etiology of the condition remains unclear. The ratio of the 2nd to the 4th (2D:4D) digit lengths has been suggested to be negatively correlated to prenatal androgen exposure. We wanted to assess differences in 2D:4D ratio between transsexuals and controls. Sixty-three male-to-female transsexuals (MFT), 43 female-to-male transsexuals (FMT), and 65 female and 58 male controls were included in the study. Photo copies of the palms and digits of the hands were taken of all subjects and 2D:4D ratios were measured, according to standard published procedures. Comparison between right-handed individuals revealed that the right-hand 2D:4D in MFT is higher than in control males but similar to that observed in control females. In FMT we found no differences in 2D:4D relative to control females. Our findings support a biological etiology of male-to-female transsexualism, implicating decreased prenatal androgen exposure in MFT. We have found no indication of a role of prenatal hormone exposure in female-to-male transsexualism.

背景与目标： : 产前暴露于雄激素与变性有关，但该病的病因尚不清楚。第2位至第4位 (2D:4D) 位长度的比率已被建议与产前雄激素暴露呈负相关。我们想评估变性者和对照组之间2D:4D比率的差异。该研究包括63名男女变性人 (MFT)，43名男女变性人 (FMT) 以及65名女性和58名男性对照。根据标准发布的程序，对所有受试者进行了手掌和手指的照片副本，并测量了2D:4D比率。右手个体之间的比较显示，MFT的右手2D:4D高于对照组男性，但与对照组女性相似。在FMT中，我们发现2D:4D相对于对照雌性没有差异。我们的发现支持了男女变性的生物学病因，这意味着MFT的产前雄激素暴露减少。我们没有发现产前激素暴露在女性对男性变性中的作用的迹象。

BACKGROUND & AIMS: :The first case of sex reassignment surgery (SRS) in our hospital was performed in January 2001; as of February, 2005, 4 cases of MTF-SRS had been performed. In the 2 most recent cases, we used penile and scrotal skin flaps to avoid complications. The depth and width of the new vagina was made to be adequate for sexual intercourse. Future attention should be focused on devising a surgical technique that will help prevent the complications of partial necrosis of the epidermal skin and wound dehiscence. Although ours is only an initial experience, we describe our surgical technique herein.

背景与目标： : 我们医院的首例变性手术 (SRS) 是在2001年1月进行的; 截至2005年2月，已进行了4例mtf-srs。在最近的2例病例中，我们使用了阴茎和阴囊皮瓣以避免并发症。使新阴道的深度和宽度足以进行性交。未来的注意力应集中在设计一种外科手术技术上，该技术将有助于防止表皮皮肤部分坏死和伤口裂开的并发症。尽管我们只是最初的经验，但我们在此描述了我们的外科手术技术。

BACKGROUND & AIMS: :Mouse strains exhibit different susceptibilities to gamma-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of gamma-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.

背景与目标： : 小鼠品系对 γ射线诱导的胸腺淋巴瘤表现出不同的敏感性。我们先前的研究将Mtf-1 (金属响应转录因子-1) 确定为候选易感基因，该基因参与调节细胞活性氧 (ROS) 的辐射诱导信号传导途径。为了揭示Mtf-1基因座赋予敏感性增加的机制，我们研究了伽马射线对体内ROS水平的早期影响及其在Mtf-1易感和抗性同基因小鼠之间的差异。在这里，我们显示了照射后4周检测到克隆生长的胸腺细胞，表明克隆扩增在很早的阶段就开始了。我们还显示，在照射后7天检查时，在Mtf-1易感小鼠中，具有较高ROS水平和增殖能力的大胸腺细胞比抗性小鼠更多，尽管在缺乏Bcl11b肿瘤抑制基因一个等位基因的小鼠中未发现这种趋势。大胸腺细胞的这种高保留，具有ROS诱导的突变的高风险，是对照射后胸腺细胞耗竭的代偿性增殖和再生反应，并且该反应可能会增加导致胸腺淋巴瘤的淋巴瘤前细胞的发育。

BACKGROUND & AIMS: In most imaging detectors, the modulation transfer function (MTF) is regarded as a good parameter to describe spatial resolution. This is undoubtedly valid for visual observation. However, the detectability of a detail is essentially a matter of signal-to-noise ratio, which is not accounted for by the MTF. In x-ray imaging, signal-to-noise ratio in the image is generally limited by incident photons statistics, often larger than readout noises. Therefore, the MTF of the detector applies to both signal and noise, and does not impair the image content. Contrast can easily be restored by image processing without altering the signal-to-noise ratio. However, a number of effects may alter very differently noise and signal(i) If the MTF significantly extends beyond half the sampling frequency, the aliasing introduced by spatial sampling can severely enhance the noise and cancel the benefit of the good signal transfer. This is illustrated by synthetic images which simulate the response of imagers with different MTFs to the same test pattern in the presence of quantum noise. (ii) Parallax and blurring by the x-ray spot size or motion are shown to degrade the transfer properties of signal, but do not affect the quantum noise; they must be treated separately. Contrary to the x-ray converter MTF, parallax directly impacts the detective quantum efficiency (DQE). Finally, it is shown that only the detective quantum efficiency can reliably describe the spatial resolution of an x-ray imaging detector in the presence of noise, parallax and blurring.

背景与目标： 在大多数成像探测器中，调制传递函数 (MTF) 被视为描述空间分辨率的良好参数。这对于视觉观察无疑是有效的。但是，细节的可检测性本质上是信噪比的问题，MTF并未考虑这一点。在x射线成像中，图像中的信噪比通常受入射光子统计信息的限制，通常大于读出噪声。因此，检测器的MTF适用于信号和噪声，并且不会损害图像内容。通过图像处理可以轻松恢复对比度，而无需更改信噪比。然而，许多影响可能会改变非常不同的噪声和信号 (i) 如果MTF显著延伸超过采样频率的一半，则由空间采样引入的混叠会严重增强噪声并抵消良好信号传输的好处。合成图像可以说明这一点，该合成图像模拟了在存在量子噪声的情况下具有不同mtf的成像器对相同测试模式的响应。(ii) x射线光斑大小或运动引起的视差和模糊显示会降低信号的传输特性，但不会影响量子噪声; 它们必须分开处理。与x射线转换器MTF相反，视差直接影响探测量子效率 (DQE)。最后，表明在存在噪声，视差和模糊的情况下，只有侦探量子效率才能可靠地描述x射线成像探测器的空间分辨率。

BACKGROUND & AIMS: :Penile skin inversion is the method of choice for vaginoplasty in male-to-female transsexuals. Rectosigmoid neocolpopoiesis should be considered only when penile skin inversion has become impossible or has not led to functional results. In this paper we describe our technique and the results of colocolpopoiesis in 7 male-to-female transsexuals.

背景与目标： : 阴茎皮肤倒置是男女变性者阴道成形术的首选方法。仅当阴茎皮肤倒置变得不可能或未导致功能结果时，才应考虑直肠乙状结肠新生。在本文中，我们描述了我们的技术以及7名男性对女性变性者的coocolpopooiesis的结果。

BACKGROUND & AIMS: :Patients with gender dysphoria are offered cross-sex hormone therapy and sex reassignment surgery to achieve the transition between the sex assigned at birth and gender identity. According to international guidelines, cross-sex hormone therapy in trans-women should lead to a psychologically and physiologically healthy body with feminized serum hormone levels, resulting in suppression of spermatogenesis. However, in a recently published multi-center study, we discovered a high proportion of patients with male serum hormone levels and qualitatively intact spermatogenesis on the day of sex reassignment surgery. The objective of this study was to review the content of 11 publications that focus on the influence of cross-sex hormone therapy on testicular morphology. These publications were identified based on a PubMed search for the key words transgender/transsexual/gender dysphoria in male-to-female persons, cross-sex hormone therapy, and testicular tissues. Whereas three publications described a marked reduction of the spermatogenic level in all patients examined, eight publications reported inconsistent results. Histological analyses showed highly variable outcomes from qualitatively normal spermatogenesis and undisturbed Leydig/Sertoli cell morphology to full testicular regression with severe cellular damage and hyalinization. Explanations for these heterogeneous findings include insufficient cross-sex hormone therapy regarding dosage or duration. As complete spermatogenesis is associated with virilized serum hormone levels, these patients may face challenges especially after sex reassignment surgery in adjusting to the abruptly established hypogonadal state following removal of the testes. These findings also suggest that contraception should be discussed, and fertility preservation should be offered during/prior to cross-sex hormone therapy. There is a need for more individualized and better-controlled cross-sex hormone therapy and post-treatment regimens. Evidence-based guidelines for attending clinicians need to be established in order to deliver the most appropriate care.

背景与目标： : 为性别不安的患者提供跨性激素治疗和变性手术，以实现出生时分配的性别和性别认同之间的过渡。根据国际指南，跨性别女性的跨性别激素治疗应导致心理和生理健康的身体，其血清激素水平女性化，从而抑制精子发生。然而，在最近发表的一项多中心研究中，我们发现在变性手术当天，男性血清激素水平和质量完整的精子发生的患者比例很高。这项研究的目的是回顾11篇出版物的内容，这些出版物着重于跨性激素疗法对睾丸形态的影响。这些出版物是根据PubMed搜索的关键字在男女之间的跨性别/变性者/性别焦虑症，跨性别激素疗法和睾丸组织中确定的。尽管有三份出版物描述了所有接受检查的患者的生精水平显着降低，但有八份出版物报告了不一致的结果。组织学分析显示，从定性正常的精子发生和不受干扰的Leydig/Sertoli细胞形态到严重的细胞损伤和透明化的睾丸完全消退，结果变化很大。对这些异质性发现的解释包括关于剂量或持续时间的跨性激素治疗不足。由于完全的精子发生与男性化的血清激素水平有关，因此这些患者可能会面临挑战，尤其是在变性手术后，在摘除睾丸后适应突然建立的性腺功能减退状态。这些发现还表明，应讨论避孕措施，并在跨性激素治疗期间/之前提供生育力保护。需要更个体化和更好控制的交叉性激素治疗和治疗后方案。为了提供最适当的护理，需要为主治临床医生建立循证指南。

BACKGROUND & AIMS: :As in laboratory animals, long-term oestrogen treatment in the human male might induce prolactinomas. We here report on PRL levels in 142 male-to-female transsexuals, treated with 100 mg cyproterone acetate and 100 micrograms ethinyloestradiol per day for 6-108 months (median 52). PRL levels varied markedly between individuals. No relation with age and length of treatment period was found. In 42 subjects in whom PRL levels were followed serially, a slight fall was measured after 12-15 months of treatment. Galactorrhoea, present in 10 of 142 subjects, was unrelated to PRL levels. In 34 subjects in whom PRL levels were measured during treatment and 3 weeks after withdrawal, PRL levels fell significantly. Dopamine in doses of 0.1 microgram/kg/min and 1.0 microgram/kg/min was administered to six subjects with PRL levels greater than 1000 mU/l and six subjects with PRL levels less than 500 mU/l. No difference in the percentage decrease of PRL levels was found between these two groups. However, administration of monoiodotyrosine, an inhibitor of central dopamine synthesis, to these two groups, induced a significantly smaller release of PRL (expressed as percentage change) in subjects with PRL greater than 1000 mU/l than in those with PRL less than 500 mU/1 possibly indicating a loss of control of central dopaminergic regulation. These findings suggest that the risk of inducing prolactinomas through cross-gender hormone treatment is likely to be small.

背景与目标： : 与实验动物一样，人类雄性长期雌激素治疗可能会诱发泌乳素瘤。我们在这里报告了142名男女变性者的PRL水平，这些变性者每天用100 mg醋酸环丙孕酮和100微克乙炔雌二醇治疗6-108个月 (中位数为52)。PRL水平在个体之间有明显差异。未发现与年龄和治疗时间的关系。在42名连续跟踪PRL水平的受试者中，治疗12-15个月后测得轻微下降。142名受试者中有10名存在半乳糖，与PRL水平无关。在治疗期间和停药后3周测量PRL水平的34名受试者中，PRL水平显着下降。将0.1微克/kg/min和1.0微克/kg/min的剂量的多巴胺施用于PRL水平大于1000的六名受试者和PRL水平小于500的六名受试者。在这两组之间，PRL水平下降的百分比没有差异。然而，向这两组施用中枢多巴胺合成抑制剂单碘酪氨酸，在PRL大于1000 mU/l的受试者中，PRL的释放明显小于PRL小于500 mU/1的受试者，这可能表明中枢多巴胺能调节的控制丧失。这些发现表明，通过跨性别激素治疗诱发泌乳素瘤的风险可能很小。

BACKGROUND & AIMS: BACKGROUND:Satisfaction with breasts, sexual well-being, psychosocial well-being, and physical well-being are essential outcome factors following breast augmentation surgery in male-to-female transsexual patients. The aim of this study was to measure change in patient satisfaction with breasts and sexual, physical, and psychosocial well-being after breast augmentation in male-to-female transsexual patients. METHODS:All consecutive male-to-female transsexual patients who underwent breast augmentation between 2008 and 2012 were asked to complete the BREAST-Q Augmentation module questionnaire before surgery, at 4 months, and later after surgery. A prospective cohort study was designed and postoperative scores were compared with baseline scores. Satisfaction with breasts and sexual, physical, and psychosocial outcomes assessment was based on the BREAST-Q. RESULTS:Thirty-five male-to-female transsexual patients completed the questionnaires. BREAST-Q subscale median scores (satisfaction with breasts, +59 points; sexual well-being, +34 points; and psychosocial well-being, +48 points) improved significantly (p < 0.05) at 4 months postoperatively and later. No significant change was observed in physical well-being. CONCLUSIONS:In this prospective, noncomparative, cohort study, the current results suggest that the gains in breast satisfaction, psychosocial well-being, and sexual well-being after male-to-female transsexual patients undergo breast augmentation are statistically significant and clinically meaningful to the patient at 4 months after surgery and in the long term. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

背景与目标：

BACKGROUND & AIMS: Previous reports of sexual orientation and gender identity in subjects with XYY karyotype are reviewed. Two patients seeking a change of sex operation and found to have an XYY karyotype are described. It is argued that an XYY karyotype may predispose to a disturbed gender identity and possibly to the development of the transsexual syndrome.

背景与目标： 回顾了先前有关XYY核型受试者的性取向和性别认同的报道。描述了两名寻求改变性别手术并发现具有XYY核型的患者。有人认为，XYY核型可能会导致性别认同受到干扰，并可能导致变性人综合症的发展。

BACKGROUND & AIMS: :From December 2001 to September 2005, the technique of total penile reconstruction with a reinnervated free latissimus dorsi myocutaneous flap was used in 22 patients (24-38 years old) with gender dysphoria. These patients were followed up for at least 11 months (range, 11-44 months). All flaps survived. Complications include hematoma (7 cases), vascular thrombosis (2 cases), partial necrosis (1 case), excessive swelling of the neophallus (3 cases), and skin graft loss at the donor site (1 case). Of the 19 patients included in the final evaluation, the transplanted muscle was able to obtain contraction in 18 (95%) cases and 8 patients (42%) had sexual intercourse by contracting the muscle to stiffen and move the neopenis. The described technique of neophalloplasty proved to be a reliable technique and the muscle movement in the neophallus can be expected in almost all cases. The muscle contraction in the neophallus leads to "paradox" erection-stiffening, widening, and shortening of the neopenis, which allows for sexual intercourse in some patients. Subsequent reconstruction of the urethra is possible.

背景与目标： : 从2001年12月到2005年9月，对22例性别不安的患者 (24-38岁) 使用了神经支配的游离背阔肌肌皮瓣进行全阴茎重建技术。对这些患者进行了至少11个月的随访 (11-44个月)。所有襟翼都活了下来。并发症包括血肿 (7例)，血管血栓形成 (2例)，部分坏死 (1例)，新球过度肿胀 (3例) 和供体部位植皮丢失 (1例)。在最终评估中包括的19例患者中，移植的肌肉能够在18例 (95% 例) 中获得收缩，并且8例 (42% 例) 通过收缩肌肉来硬化和移动新肾而进行性交。所描述的神经成形术技术被证明是一种可靠的技术，几乎在所有情况下都可以预期神经成形术中的肌肉运动。neophallus的肌肉收缩导致 “悖论” 勃起-neopenis的僵硬，加宽和缩短，这允许某些患者进行性交。尿道的后续重建是可能的。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the incidence of venous thromboembolism (VTE) in transsexual patients and the value of screening for thrombophilia in this population. DESIGN:Retrospective cohort study. SETTING:Academic research institution. PATIENT(S):Two hundred fifty-one transsexuals (162 male-to-female [MtF] and 89 female-to-male [FtM] transsexuals). INTERVENTION(S):Screening for activated protein C (aPC) resistance, antithrombin III, free protein S antigen, and protein C deficiency. MAIN OUTCOME MEASURE(S):Incidence of thrombophilic defects and VTE during cross-sex hormone therapy. RESULT(S):Activated protein C resistance was detected in 18/251 patients (7.2%), and protein C deficiency was detected in one patient (0.4%). None of the patients developed VTE under cross-sex hormone therapy during a mean of 64.2 +/- 38.0 months. There was no difference in the incidence of thrombophilia comparing MtF and FtM transsexuals (8.0% [13/162] vs. 5.6% [5/89], respectively). CONCLUSION(S):VTE during cross-sex hormone therapy is rare. General screening for thrombophilic defects in transsexual patients is not recommended. Cross-sex hormone therapy is feasible in MtF as well as in FtM patients with aPC resistance.

背景与目标：

BACKGROUND & AIMS: :The purpose of this research is to achieve uniform spatial resolution in CT (computed tomography) images without hardware modification. The main idea of this study is to consider geometry optics model, which can provide the approximate blurring PSF (point spread function) kernel, which varies according to the distance from X-ray tube to each pixel. The FOV (field of view) was divided into several band regions based on the distance from X-ray source, and each region was deconvolved with different deconvolution kernels. Though more precise calculation for the PSF for deconvolution is possible as the number of subbands increases, we set the number of subbands to 11. 11 subband settings seem to be a balancing point to reduce noise boost, while MTF (modulation transfer function) increase still remains. As the results show, subband-wise deconvolution makes image resolution (in terms of MTF) relatively uniform across the FOV. The results show that spatial resolution in CT images can be uniform across the FOV without using additional equipment. The beauty of this method is that it can be applied to any CT system as long as we know the specific system parameters and determine the appropriate PSF for deconvolution maps of the system. The proposed algorithm shows promising result in improving spatial resolution uniformity while avoiding the excessive noise boost.

背景与目标： : 这项研究的目的是在无需硬件修改的情况下在CT (计算机断层扫描) 图像中实现统一的空间分辨率。这项研究的主要思想是考虑几何光学模型，该模型可以提供近似模糊的PSF (点扩散函数) 内核，该内核根据从x射线管到每个像素的距离而变化。根据距x射线源的距离，将FOV (视场) 划分为几个带区域，并使用不同的反卷积核对每个区域进行反卷积。尽管随着子带数量的增加，可以对PSF进行更精确的反卷积计算，但我们将子带数量设置为11。11子带设置似乎是减少噪声增强的平衡点，而MTF (调制传递函数) 的增加仍然存在。结果表明，子带反卷积使整个FOV的图像分辨率 (就MTF而言) 相对均匀。结果表明，CT图像的空间分辨率可以在整个FOV上均匀，而无需使用其他设备。这种方法的优点在于，只要我们知道特定的系统参数并为系统的反卷积图确定合适的PSF，它就可以应用于任何CT系统。所提出的算法在改善空间分辨率均匀性的同时避免了过度的噪声增强方面显示出有希望的结果。

BACKGROUND & AIMS: :Metal responsive element (MRE)-binding transcription factor-1 (MTF-1) is a zinc finger (ZF) transcription factor that plays a key role in heavy metal homeostasis by regulating relevant genes in response to metals. MTF-1 is known to be activated by heavy metals such as Zn and Cd, but the mechanism of activation remains unclear. In the present study, Cys and His residues of human MTF-1 (hMTF-1), some of which may be involved in interaction with metals or with each other, were screened for their contribution to Zn-dependent transcription. To avoid poor induction ratios of previous transfection assays, we re-examined experimental conditions to establish an assay able to correctly detect Zn-responsive transcription. Using this assay, a series of Cys and/or His substitution mutants were analyzed over the entire hMTF-1 molecule. In five out of the six ZFs (ZF1 to ZF5), Cys mutations that disrupt the ZF structure abolished response to Zn. Of these, ZF5 was shown for the first time to be essential for Zn-responsive transcription, despite it being unnecessary for Zn-induced DNA binding. These results indicate that Zn activation of hMTF-1 involves an additional process besides induction of DNA binding activity. Our assay also confirmed the importance of Cys in the acidic activation domain, as well as those in the C-terminal Cys cluster, implicated in transcription in other studies. The identified Cys residues might contribute to metal response of hMTF-1 through direct metal binding and/or intramolecular interactions, analysis of which will be helpful in understanding the mechanism of metal response.

背景与目标： : 金属响应元件 (MRE) 结合转录因子-1 (MTF-1) 是锌指 (ZF) 转录因子，通过调节相关基因对金属的反应，在重金属稳态中起关键作用。已知MTF-1被重金属 (例如Zn和Cd) 活化，但活化机理尚不清楚。在本研究中，筛选了人MTF-1 (hMTF-1) 的Cys和His残基 (其中一些可能与金属或彼此相互作用有关) 对Zn依赖性转录的贡献。为了避免先前转染测定的诱导率差，我们重新检查了实验条件，以建立能够正确检测Zn响应转录的测定方法。使用该测定法，在整个hMTF-1分子上分析一系列Cys和/或His取代突变体。在六个ZF (ZF1至ZF5) 中的五个中，破坏ZF结构的Cys突变消除了对Zn的反应。其中，尽管ZF5对于Zn诱导的DNA结合是不必要的，但ZF5首次被证明对Zn反应性转录至关重要。这些结果表明，除了诱导DNA结合活性外，hMTF-1的Zn活化还涉及其他过程。我们的分析还证实了Cys在酸性激活结构域以及C末端Cys簇中的重要性，这与其他研究中的转录有关。鉴定出的Cys残基可能通过直接金属结合和/或分子内相互作用有助于hMTF-1的金属响应，对其进行分析将有助于理解金属响应的机理。