多囊卵巢综合征肾上腺高雄激素的病因探讨

卵巢分泌睾酮是多囊卵巢综合征中雄激素过量的主要来源,一般对高雄激素血症的病因重点关注卵巢睾酮水平的升高,而对肾上腺分泌雄激素--硫酸脱氢表雄酮参与多囊卵巢综合征研究较少.另外,性激素结合球蛋白水平高低决定雄激素的生物活性状态.因而多囊卵巢综合征中肾上腺类固醇激素的合成可能是多囊卵巢综合征中高雄激素环境形成的决定因素之一.该文综述了近年来肾上腺雄激素在多囊卵巢综合征发病中的作用,旨在为多囊卵巢综合征治疗提供理论依据.     

卵巢源雄激素过多症和肾上腺源雄激素过多症

雄激素过多症是临床常见的内分泌紊乱性疾病,雄激素水平升高一直是困惑研究者的难题。临床对雄激素来源的诊断非常有限,而且缺少特定有效的检查及相关临床信息。高雄激素血症中雄激素不止来源于一种腺体,卵巢是公认合成雄激素的腺体,而肾上腺也是合成雄激素的重要腺体之一。多囊卵巢综合征和自发性雄激素过多症中,肾上腺所分泌的雄激素是多因素共同作用的结果,包括高胰岛素血症、甾体激素代谢紊乱、卵巢激素合成增加。然而,伴有脱氢表雄酮硫酸盐水平升高的高雄激素患者体重减轻,胰岛素水平较低,代谢情况良好。该文从分泌雄激素的腺体—卵巢和肾上腺两个方面,对3种常见的雄激素过多症(即多囊卵巢综合征、自发性雄激素过多症、非典型性21-羟化酶缺乏症)的雄激素水平分别进行阐述。     

多囊卵巢综合征患者血浆中肾上腺髓质激素水平

多囊卵巢综合征（PCOS）是育龄期妇女极为常见的内分泌疾病，发病率为3％-10％，临床特征为月经失调、高雄激素血症和胰岛素抵抗（IR）。至今其发病机制仍存在争议，下丘脑．垂体一卵巢轴功能的改变、肥胖、IR、卵巢和／或肾上腺来源的雄激素过多、类固醇激素生成障碍等均在发病中起一定的作用。     

多囊卵巢综合征患者血清胰岛素水平测定及其意义

目的: 探讨多囊卵巢综合征 (PCOS) 患者血清胰岛素水平变化及意义。方法: 采用全自动化学发光法测定 114例PCOS患者血清胰岛素水平, 其中高雄激素组 35例, 雄激素正常组 79例, 两组进行对照。结果: PCOS高雄激素组空腹血清胰岛素水平 (14 .32±9. 01) mIU/L, 对照组 (雄激素正常组) 血清空腹胰岛素水平 (10 .65±7 .97) mIU/L, 两组比较差异有显著性 (t=3 .162, P<0 .05)。结论: 胰岛素参与PCOS高雄激素的病理过程。     

多囊卵巢综合征遗传学研究进展

多囊卵巢综合征(PCOS)是育龄妇女最常见的生殖内分泌紊乱性疾病,具有高度遗传异质性,其致病原因迄今不明。PCOS有高度的家族聚集性,提示遗传因素在发病中起重要作用。遗传学研究表明,影响这些激素代谢和调节的多种基因参与了该病的发生,PCOS典型的临床表现使研究者着重关注影响雄激素代谢、胰岛素抵抗等基因,近年来有七十余种基因在研究中。就与雄激素合成和调节有关的基因,与胰岛素抵抗和代谢紊乱有关的基因,与炎症有关的基因的研究进展作综述。     

胰岛素增敏剂在治疗多囊卵巢综合征中的作用

多囊卵巢综合征(PCOS)的主要病理生理学变化是代偿性高胰岛素血症(HI)和胰岛素抵抗(IR),由此产生①高雄激素(HA)和高黄体生成激素(HLH)引起的无排卵性生育障碍;②糖脂代谢异常导致远期代谢并发症.因此利用胰岛素增敏剂(ISA)可降低血胰岛素(INS)水平,使卵巢和肾上腺合成及释放雄激素减少,改善生殖功能,防止代谢并发症 .     

多囊卵巢综合征遗传学研究进展

多囊卵巢综合征(PCOS)是育龄妇女最常见的生殖内分泌紊乱性疾病,具有高度遗传异质性,其致病原因迄今不明.PCOS有高度的家族聚集性,提示遗传因素在发病中起重要作用.遗传学研究表明,影响这些激素代谢和调节的多种基因参与了该病的发生,PCOS典型的临床表现使研究者着重关注影响雄激素代谢、胰岛素抵抗等基因,近年来有七十余种基因在研究中.就与雄激素合成和调节有关的基因,与胰岛素抵抗和代谢紊乱有关的基因,与炎症有关的基因的研究进展作综述.     

微小RNA在多囊卵巢综合征病因学研究中的新进展

多囊卵巢综合征（PCOS）是一种常见的生殖内分泌疾病,其主要特征是高雄激素血症、稀发排卵或无排卵、卵巢多囊样改变及胰岛素抵抗。微小RNA（miRNA）是一类小分子非编码RNA,在转录后水平对靶基因进行调控。miRNA可以通过调节卵巢颗粒细胞增殖和凋亡影响卵泡发育、排卵与闭锁;通过影响雄激素的合成和释放,导致内分泌紊乱;通过调节糖代谢及胰岛素敏感性,诱导胰岛素抵抗的产生,从而参与PCOS的发病过程。现就miRNA在PCOS病因学研究中的进展进行综述。     

多囊卵巢综合征及卵巢打孔术

多囊卵巢综合征（polycystic ovarian syndrome,PCOS）是一种内分泌紊乱性疾病,是无排卵性不孕的主要病因。氯米芬（clomifene citrate,CC）是无排卵PCOS的首选一线促排卵治疗。随着腹腔镜手术的发展,腹腔镜下卵巢打孔术（laparoscopic ovarian drilling,LOD）已成为治疗无排卵PCOS广泛应用的微创治疗方式,当CC抵抗时LOD可作为首选促排卵方法。LOD术中需特别强调穿刺针应垂直卵巢,充分冲洗卵巢,预防医源性粘连。PCOS患者LOD术后,卵巢功能、月经及内分泌可得到明显改善。研究显示显著肥胖、雄激素过多症、长时间不孕可能预测LOD抵抗。术前黄体生成激素（LH）高水平LOD术后排卵妊娠的概率更高。LOD较促性腺激素治疗避免了多胎妊娠、卵巢过度刺激综合征（OHSS）等并发症。     

多囊卵巢综合征的妇女血浆肾素总量增高

多囊卵巢综合征(PCOS)是一种伴有促性腺激素分泌异常、雄激素增多症以及慢性无排卵症。PCOS是先天性畸形还是下丘脑、垂体水平或者周围组织引起的卵巢及肾上腺过度分泌雄激素仍有争议。临床异常表现及实验室特征都有力地说明了PCOS病因是多     

The role of 5alpha-reduction in steroid hormone physiology

A role for 5alpha-reduction in androgen physiology was first established with the recognition that dihydrotestosterone, the 5alpha-reduced metabolite of testosterone, is formed in many androgen target tissues, binds to the androgen receptor with greater affinity than testosterone, and plays an essential role in virilization of the urogenital sinus and urogenital tubercle during male development. Two 5alpha-reductases perform this reaction, and both isoenzymes utilize NADPH as cofactor and have broad specificity for steroids containing a delta4,3-keto configuration. 5alpha-Reduction, which is essentially irreversible, flattens the steroid molecule because of altered relation of the A and B rings, and stabilizes the hormone-receptor complex. Studies involving in vitro reporter gene assays and intact mice in which both isoenzymes are disrupted, indicate that the fundamental effect of dihydrotestosterone formation is to amplify hormonal signals that can be mediated by testosterone at higher concentrations. 5alpha-Reduction also plays a role in the action of other steroid hormones, including the plant growth hormone, brassinolide, the boar pheromones, androstanol and androstenol, progesterone (in some species), and, possibly, aldosterone and cortisol. The fact that the reaction is important in plants and animals implies a fundamental role in steroid hormone action.     

雄激素与女性生殖

雄激素是男性体内含量最多、最重要的一种类固醇激素。在女性体内,雄激素也是不可或缺的。女性体内雄激素来源于卵巢和肾上腺,具有生物活性的雄激素包括睾酮（T）和双氢睾酮（DHT）,肾上腺雄激素在外周组织转化为睾酮。一方面睾酮在女性体内经过芳香化酶的作用合成雌激素,另一方面睾酮和DHT结合雄激素受体（AR）进入细胞核内调控靶基因的转录。AR除了分布于卵巢外,还在大脑、肌肉、骨骼、皮肤、肾脏、肝脏等外周非生殖器官表达。在卵泡发生和成熟中,雄激素也起重要作用。过多雄激素,常与多囊卵巢综合征相关。结合女性体内雄激素的靶器官,综述雄激素在女性卵巢和外周非靶器官的作用,及其与女性生殖相关的事件如乳腺癌的关系。     

Immunolocalization of sex steroid hormone receptors in the canine uterine tube and their relation to sex steroid hormone concentrations

The aim of this immunohistochemical study was to describe the cellular distribution of the estrogen receptor-alpha (ERalpha), progesterone receptor (PR) and androgen receptor (AR) in canine uterine tubes. Samples of uterine tubes were taken from dogs in different stages of the estrous cycle, and dogs that were pregnant or had just delivered. Nuclear staining for sex steroid hormone receptors was observed in the surface epithelium, stromal cells and smooth muscle cells of the muscular layer. Only slight differences in staining pattern were observed between the ampulla and fimbriae. The staining for ERalpha and PR showed changes throughout the estrous cycle. Some of these changes were related to changing concentrations of sex steroid hormones. High staining scores for ERalpha and PR were found during proestrus and low scores during early metestrus. The staining for AR showed only minor cyclic changes. However, during proestrus and estrus, cytoplasmic staining for AR was observed in differentiated secretory epithelial cells, when nuclear staining in these cells was nearly absent. For the three hormone receptors, stromal cells generally stained with a higher intensity than epithelial cells. It is likely that many steroid hormone actions on the epithelium are mediated through stromal cells. During pregnancy, rather high staining scores were found for ERalpha and AR in the uterine tube. This is in contrast to observations in the canine pregnant uterus.     

The aging ovary

During reproductive life, ovarian steroid biosynthesis is gonadotropin dependent and occurs in theca and granulosa cells. In the menopausal ovary, there is atresia of ovarian follicles, with sparing of the androgen-producing theca-interstitial cell component. The aging ovary, therefore, produces significantly reduced amounts of estrogen, with continued, though decreased, androgen production. After menopause, ovarian estradiol biosynthesis is minimal, with circulating estrogen being derived principally from peripheral aromatization of ovarian and adrenal androgens. Androgen biosynthesis from the adrenal gland, in addition to that from the ovary, decreases with age. Although ovarian androgen production declines with age, there is not an abrupt decrease as is seen with ovarian estrogen levels at the time of menopause. The biological activity of these steroids, either before or after menopause, depends on the amount of steroid available in the unbound fraction. To this end, sex hormone-binding globulin (SHBG) levels are an important determinant of hormone action. Not only does the concentration of SHBG influence the biological effect of testosterone and estradiol, but these steroids also regulate SHBG concentrations.     

Endocrine potency of wastewater: contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays

Industrial and municipal effluents are important sources of endocrine disrupting compounds (EDCs) discharged into the aquatic environment. This study investigated the endocrine potency of wastewater and the cleaning efficiency of two typical urban Danish sewage treatment plants (STPs), using chemical analysis and a battery of bioassays. Influent samples, collected at the first STP grate, and effluent samples, collected after the sewage treatment, were extracted using solid phase extraction. Extracts were analyzed for the content of a range of industrial chemicals with endocrine disrupting properties: phthalate metabolites, parabens, industrial phenols, ultraviolet screens, and natural and synthetic steroid estrogens. The endocrine disrupting bioactivity and toxicity of the extracts were analyzed in cell culture assay for the potency to affect the function of the estrogen, androgen, aryl hydrocarbon, and thyroid receptors as well as the steroid hormone synthesis. The early-life stage (ELS) development was tested in a marine copepod. The concentrations of all analyzed chemicals were reduced in effluents compared with influents, and for some to below the detection limit. Influent as well as effluent samples from both STPs were found to interact with all four receptors and to interfere with the steroid hormone synthesis showing the presence of measured EDCs. Both influent samples and one of the effluent samples inhibited the development of the copepod Acartia tonsa. In conclusion, the presence of EDCs was reduced in the STPs but not eliminated, as verified by the applied bioassays that all responded to the extracts of effluent samples. Our data suggest that the wastewater treatment processes are not efficient enough to prevent contamination of environmental surface waters.     

Competitive binding comparison of endocrine-disrupting compounds to recombinant androgen receptor from fathead minnow, rainbow trout, and human

Typically, in vitro hazard assessments for the identification of endocrine-disrupting compounds (EDCs), including those outlined in the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Tier 1 Screening protocols, utilize mammalian receptors. Evidence, however, exists that fish sex steroid hormone receptors differ from mammalian receptors both structurally and in their binding affinities for some steroids and environmental chemicals. Most of the binding studies to date have been conducted using cytosolic preparations from various tissues. In the present study, we compare competitive binding of a set of compounds to full-length recombinant rainbow trout androgen receptor alpha (rtAR), fathead minnow androgen receptor (fhAR), and human androgen receptor (hAR), each expressed in COS cells. Saturation binding and subsequent Scatchard analysis using [3H]R1881, a high-affinity synthetic androgen, revealed an equilibrium dissociation constant (Kd) of 0.11 nM for the rtAR, 1.8 nM for the fhAR, and 0.84 nM for the hAR. Compounds, including endogenous and synthetic steroids, known mammalian antiandrogens, and environmental compounds, were tested for competitive binding to each of the three receptors. Overall, agreement existed across receptors as to binding versus nonbinding for all compounds tested in this study. Minor differences, however, were found in the relative order of binding of the compounds to the individual receptors. Studies such as these will facilitate the identification of EDCs that may differentially affect specific species and aid in the development and support of future risk assessment protocols.     

The role of adrenal and gonadal hormones in the pathogenesis of autoimmune polyarthritis

A growing body of recently published results suggest the role of adrenal androgens in the onset and development of chronic inflammatory process due to autoantigens. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA)--the major androgen products of the adrenal gland--have immunosuppressive effect inhibiting interleukin-6 production and substantially determining acute phase reaction. Decreased serum levels of DHEA and DHEAS has been observed in most of autoimmune diseases. Recent data suggest that adrenal hypoandrogenism comes from disturbed neuroendocrine, regulation due to hypothalamic effect of the inflammatory cytokines. On the other side, decreased adrenal androgen activity negatively influences the anabolic tonus of steroid hormone system while a relative enhancement of catabolic pressure occurs by the glucocorticoids. Moreover, the hypothalamus-hypophysis-gonadal axis can also be involved, resulting shifts in serum levels of prolactin, estrogens and gonadal androgens. All these hormonal changes can be summarised in decreasing the immunosuppressive tonus. This hypothesis connects the endocrine dysregulation with the development of autoimmune disorders. The new results promise not only a basically different theory of chronic inflammation but they will permit using new diagnostic tools as well as inducing substantially new and more effective therapeutic approaches.