黄体生成素β Gly102Ser基因多态性与多囊卵巢综合征的相关性研究

目的探讨黄体生成素β(Luteinizing hormoneβ-subunit,LHβ)Gly102Ser及黄体生成素受体(Luteinizing hormone receptor,LHR)基因多态性与PCOS的相关性。方法应用聚合酶链反应-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)检测LHβGly102Ser多态性,分析LHβ基因多态性与多囊卵巢综合征(polycystic ovary syndrome,PCOS)的相关性。结果 PCOS组中LHβGly102Ser基因有14例突变型,占3.3%。对照组中3例突变,占1.1%;PCOS组LHβGly102Ser基因突变率显著高于对照组(P=0.006);LHβGly102Ser基因突变型的血清基础LH水平低于对照组(P0.05),但突变组有降低趋势;PCOS组内血清LH2mmol/L的患者,LHβ基因Gly102Ser发生突变的比例显著增加(P=0.003)。结论 PCOS人群中存在LHGly102Ser基因多态性,此多态性与PCOS有明显的相关性。LHβGly102Ser基因多态性可能是PCOS发病的危险因素之一。     

多囊卵巢综合征卵泡颗粒细胞提前对黄体生成素反应

目的： 探讨多囊卵巢综合征（PCOS）卵泡液中激素和颗粒细胞黄体生成素（LH）受体mRNA表达的关系。方法: 对PCOS组12例和对照组15例患者于月经周期的第7-10 d手术获取卵泡和卵泡液，采用微粒子化学发光法检测卵泡液中卵泡刺激素（FSH）、LH、孕酮（P）、雌二醇（E2）和胰岛素（insulin）的水平，采用ELISA检测卵泡液中雄烯二酮（A）的水平，对颗粒细胞和卵泡膜细胞LH受体mRNA进行RT-PCR半定量检测。结果: PCOS组卵泡液中LH［（3.8±2.1 vs 1.7±0.8)U/L, P<0.01］、A［(600.0±373.4 vs 212.4±205.4)μg/L, P<0.05］和颗粒细胞LH受体mRNA的表达(0.29±0.16 vs 0.12±0.13, P<0.01)显著高于对照组， PCOS组卵泡的颗粒细胞提前表达LH受体mRNA; 对照组卵泡直径小于 7 mm 时，RT-PCR检测不到颗粒细胞LH受体mRNA表达，而PCOS组卵泡直径达到 4 mm 时，发现颗粒细胞LH受体mRNA已提前表达。颗粒细胞LH受体mRNA的表达与卵泡液中LH(r=0.67,P<0.01)、胰岛素(r=0.51,P<0.05)及卵泡膜细胞LH受体mRNA表达的水平(r=0.6,P<0.01)呈正相关。结论: PCOS的卵泡液中存在高水平的LH，PCOS卵泡颗粒细胞提前对LH反应，颗粒细胞和卵泡膜细胞合成A和P增强，这可能是PCOS卵泡发育停滞的原因之一。     

多囊卵巢综合征患者血清相关性腺激素结果分析

目的本文主要探讨血清总睾酮(total testosterone,TT)、雄烯二酮(androstendione,AND)以及促黄体生成素(luteinizing hormone,LH)/促卵泡刺激素(follicle stimulating hormone,FSH)比值对多囊卵巢综合征(PCOS)的诊断灵敏度,PCOS患者血清AND与TT、LH、FSH浓度及LH/FSH比值是否具有相关性,以及探究不同年龄段PCOS患者血清各相关生化指标是否有显著差异。方法回顾性地分析了121例PCOS患者血清生化指标,包括 LH、FSH、AND、TT和计算出的 LH/FSH 比值。PCOS 患者经临床表现、体格检查、血清 TT 测定结合卵巢彩超结果确诊,根据年龄以20岁为界将患者分为青春期和成年期两组。结果经统计,PCOS 患者血清 TT 阳性率为59%,AND 阳性率为62%,有33%的患者LH/FSH比值大于2。TT联合AND检测可以提高PCOS的诊断灵敏度至74%。TT 与 AND 经Pearson 相关性分析, P =0.006(<0.05 ),有线性相关关系,且为正相关,LH、FSH 和 LH/FSH 比值与 TT、AND 均无线性相关关系。经 t 检验分析,在青春期与成年期两组 PCOS 患者间,青春期组患者的血清 TT 水平与成年期组相比,青春期组明显高于成年期组,差异有统计学意义, P =0.002(<0.05)。两组的AND、LH、FSH 水平和 LH/FSH 比值差异均无统计学意义。结论本研究表明血清TT 联合AND 检测可以提高PCOS 患者的诊断灵敏度,PCOS 患者血清AND浓度与TT 呈线性正相关,与LH、FSH浓度及LH/FSH比值均不具有线性相关关系。青春期患者血清TT明显高于成年期组,AND、LH、FSH浓度及LH/FSH比值差异无统计学意义。     

短效GnRH—a在促排卵周期中诱导卵泡成熟与排卵的研究

目的 探讨在缺乏内源性LH峰的促排卵周期中,使用短效GnRH-a诱导卵泡成熟与排卵的临床效果及适宜剂量.方法 在使用HMG的促排卵周期中,当卵泡成熟时,缺乏内源性LH峰的患者,随机分成研究组(107周期)与对照组(93周期),分别给予短效曲普瑞林和HCG,监测尿LH值变化,并在卵泡破裂日行IUI,给予黄体史持.结果 两组的排卵率比较无统计学差异(P＞0.05);研究组卵巢过度刺激综合征(OHSS)的发生率较对照组有明显降低,差异有统计学意义(P＜0.05);在研究组中分别使用0.1mg和0.2mg短效曲普瑞林诱发排卵,其排卵率差异无统计学意义(P＞0.05);尿LH值在药物注射后4h0.2mg组明显高于0.1mg组,差异有统计学意义(P＜0.05).研究组在用药前后的尿LH值与对照组相比,在用药后4h、8h、24h、32h的尿LH值差异均有统计学意义(P＜0.05).两组的临床妊娠率、双胎妊娠率及早期自然流产率比较差异无统计学意义(P＞0.05).结论 在缺乏内源性LH峰的促排卵周期中,短效GnRH-a可有效诱导卵泡成熟及排卵发生,获得与HCG相似的排卵效果及妊娠结局,可有效降低OHSS发生;0.1mg和0.2mg的短效曲普瑞林,均可有效诱发内源性LH峰出现;需要常规给予黄体支持.     

PCOS遗传基因研究进展

多囊卵巢综合征(PCOS)是育龄妇女常见的生殖内分泌紊乱性疾病,为异质性病变,临床表现各异,其主要内分泌特征为高雄激素血症、高胰岛素血症和胰岛素抵抗、LH水平和LH/FSH比值升高。迄今为止,PCOS的发病机制还不清楚,PCOS患者的高度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PCOS的发生发展过程。     

PCOS患者血浆leptin和血清T、E2、FSH、LH、PRL检测的临床意义

目的：探讨多囊卵巢综合征（PCOS）患者血浆leptin和血清T、E2、FSH、LH、PRL水平的变化及临床意义。方法：应用放射免疫分析和发光法对31例PCOS患者进行了血浆leptin和血清T、E2、FSH、LH、PRL测定,并以正常妇女作对照。结果：PCOS患者血浆leptin和血清T、LH、PRL水平非常显著地高于正常妇女组（P〈0.01）,FSH、E2水平与正常妇女组比较无显著性差异（P〉0.05）,且血浆leptin水平与血清T、LH、PRL水平呈正相关（r=0.5784、0.5411、0.6082,P〈0.01）。结论：检测PCOS患者血浆leptin和血清T、E2、FSH、LH、PRL水平的变化与疾病的发生和发展密切相关。     

多囊卵巢综合征患者血清抑制素B水平的分析

目的：探讨抑制素B（inhibin,INH-B）水平在多囊卵巢综合征（PCOS）患者血清中的变化及其与体重指数（BMI）的关系。方法：筛选PCOS患者40例,根据体重指数（BMI）分为肥胖组和非肥胖组并检测血清中的抑制素B（INH-B）、胰岛素生长因子-I（IGF-I）、空腹胰岛素（In）、瘦素（leptin）、黄体生成素（LH）、卵泡刺激素（FSH）、人体催乳素（PRL）、雌二醇（E2）和睾酮（T）,另取40例排卵正常、无怀孕妇女做对照分析。结果：PCOS患者肥胖组leptin、In、LH、T水平明显高于非肥胖组,INH-B、IGF水平则明显低于非肥胖组,差异有统计学意义（P〈0.05）;且肥胖组的LH与INH-B呈负相关（r=-0.735,P〈0.05）,非肥胖组的LH与INH-B无明显相关性。非肥胖组INH-B、IGF、LH、T水平明显高于对照组,差异有统计学意义（P〈0.05）。结论：INH-B与多囊卵巢综合征（PCOS）发生有关,且作为PCOS特征的肥胖又影响着INH-B的作用和水平。     

二甲双胍对多囊卵巢综合征患者胰岛素抵抗及排卵的影响

目的探讨胰岛素增敏剂二甲双胍对多囊卵巢综合征（PCOS）的胰岛素抵抗及排卵的治疗效果。方法把60例月经稀发或闭经的PCOS患者，随机分成三组，20例给予克罗米酚治疗（克罗米酚组），20例给予二甲双胍治疗（二甲双胍组），20例给予二甲双胍及克罗米酚联合治疗，在用药8周后比较各组治疗前后体重指数、腰臀比、黄体生成素（LH）、黄体生成素（LH）与卵泡刺激素（FSH）比值、睾酮及血清胰岛素水平与排卵率的变化。结果经用二甲双呱治疗8周后，测定血LH、LH／FSH、睾酮、血清胰岛素水平有明显下降，差异有显著性（P〈0．01）。二甲双胍组中有8例诱发排卵，克罗米酚组有12例诱发排卵，联合治疗组有18例诱发排卵。结论二甲双胍能改善并诱发排卵功能，并增强多囊卵巢综合征患者对克罗米酚的敏感性。     

多囊卵巢综合征患者性激素水平与胰岛素抵抗相关性分析

目的探讨多囊卵巢综合征(PCOS)的病因、发病机理及寻找最佳的治疗方案提供依据。方法通过放射免疫(RIA)法测患者胰岛素释放试验,酶法测糖耐量试验,电化学发光免疫分析(ECLIA)法测血清LH、FSH、E2、P、T水平。结果表明28.2%患者有胰岛素抵抗(IR),13.1%有IR和糖耐量受损,5.5%糖耐量受损。单纯IR患者中,肥胖者占35.7%;单纯糖耐量受损者中,肥胖者占36.3%;IR伴糖耐量受损者中,肥胖者占34.6%;肥胖组LH、LH/FSH、E2、T水平与非肥胖组之间无显著性差异(P0.05);而肥胖组与非肥胖的空腹血糖及空腹胰岛素水平有显著性差异(P0.05);肥胖者与非肥胖者月经周期及卵泡数目两指标有显著性差异(P0.05)。结论有较多PCOS患者存在IR或糖耐量受损;在IR和糖耐量受损的患者中,肥胖者占有较高的比重,肥胖可促进IR形成;肥胖可加重IR和生殖功能障碍。     

多囊卵巢综合征妇女激素与血脂水平的相关性研究

本文以34例PCOS妇女和20例正常月经周期妇女为研究对象,通过测定两组激素和血脂水平,了解两组血清激素和血脂的差别。同时,应用逐步回归方法,建立了Tch和HDLc的回归模型。结果表明PCOS组LH、LH/FSH、睾酮明显高于对照组(P<0.05),而E_2低于对照组黄体期水平(P<0.05)。空腹血清胰岛素与Tch高于对照组,而HDLc低于对照组(P<0.05)。PCOS妇女Tch和HDLc分别与胰岛素和睾酮呈线性关系。由此,推测PCOS妇女的高胰岛素和高雄激素水平可能分别是致Tch升高和HDLc降低的原因之一。从而为防止PCOS妇女心血管疾病危险性提供了发病学基础。     

Influence of abnormal structure beta chain of luteinizing hormone on endocrinological kinetics of luteinizing hormone and gynecologic diseases

With recent progress in endocrinology and in procreation physiology, the importance of kinetics of pituitary gonadotropin has been increasing, and the measurement method has been improved. In the present study, however, we found inconsistency in measured LH values between IRMA (SPAC-S LH) as the conventional method and CLEIA (IMMULYZE LH) as the newly developed method. The inconsistency between the SPAC-S LH value and the IMMULYZE LH value was observed in 10.0% of the healthy group and in 12.5% of the patient group. The cause of this discrepancy was due to a reaction of the SPAC-S LH of the intact LH monoclonal antibodies to the LH with the abnormal structure beta chain by two point mutation in the LH beta gene. The response of LH-RH test varied depending on the measurement reagent of LH in patients who had the LH with the abnormal structure beta chain, which made it difficult to determine the lesion and histological grading regarding the ovulation mechanism. Therefore, in patients with abnormal beta chain, an accurate treatment protocol was indeterminate. In this study, although a relationship between various gynecological diseases and the point mutation of LH was not clarified, we suggest that LH of the abnormal structure beta chain may cause excessive secretion in the early stage, and lead to some effect on physical activities.     

Steroidogenic action of 2 analogs of ovine LH on cells isolated from ovine corpus luteum

Lysine residues appear to play an important role in the biological activity of luteinizing hormone or lutropin (LH). Some derivatives obtained by chemical modification such as N-methylated LH exhibit the same hormonal activity than LH in the different steps of the mechanism of steroidogenesis. Some others, on the contrary, preserve the hormonal activity only at some steps. In this work was investigated the action of ovine LH and some derivatives on isolated cells prepared from ovine corpora lutea. Guanidinated LH (which is able to bind to LH receptors in Leydig cells but whose steroidogenic potency is very low) exhibits no binding or steroidogenic activity in the female (sheep or rat). As a consequence guanidyl LH can act as an inhibitor of LH action in the male (Leydig cells).     

Gonadotrophin surge-inhibiting/attenuating factor governs luteinizing hormone secretion during the ovarian cycle: physiology and pathology

The stabilization of low luteinizing hormone (LH) concentrationsduring the period of the ovarian cycle preceding the mid-cycleLH surge seems to be of importance for embryo viability andsurvival. Several studies have stressed the importance of thetimely excess of threshold levels of LH for optimal oocyte quality:LH already initiates the resumption of meiosis when a relativelylow threshold level is reached, whereas a further outburst ofLH release is necessary to reach the threshold level to induceovulation. Hence, the mechanism of LH release should have theability, on the one hand, to limit the LH secretion rate, andon the other, to allow an increased secretion rate, as duringthe LH surge. The functional antagonistic coupling of gonadotrophin-releasinghormone (GnRH) and the ovarian protein gonadotrophin surge-inhibitingfactor or -attenuating factor (GnSIF/AF) provides such a modeof action for the control of LH concentration during the ovariancycle. One of the important regulatory steps in this processis the de-novo synthesis of the so far unidentified pituitaryproteins induced by GnRH. The induction of these proteins isa prerequisite for the increase in the rate of LH release. Becausetheir synthesis is a time-consuming process, the effect becomesvisible in the typical biphasic pituitary LH responses to thepulsatile or continuous administration of GnRH: initially low,with an increase after some time. This phenomenon is also knownas the GnRH self-priming action. It is assumed that the synthesisof these self-priming-associated proteins is necessary to eliminatethe inhibitory effect of GnSIF/AF. GnSIF/AF eliminates the effectof self-priming by neutralizing the biological activity of thepituitary proteins, which are responsible for the increasedrate of LH release. Thus, the pituitary gland is kept in a GnRH-hyporesponsivestate. The major advantage of such a slow protein synthesisdependentregulatory mechanism is that it prevents sudden increases inthe LH secretion rate in response to GnRH. Thus it stabilizeslow LH concentrations to prevent the premature reinitiationof meiosis. However, the enhanced secretion of GnRH and/or thesuppressed release or action of GnSIF/AF may finally lead tothe restoration of the intrinsic LH responsiveness of the gonadotrophsat the start of the mid-cycle LH surge. The antagonistic interactionbetween GnRH and GnSIF/AF, and its implication in the controlof LH release under physiological and pathological conditions,are discussed.     

Endocrinology: Clinical significance of invisible or partially visible luteinizing hormone

It is well known that luteinizing hormone (LH), like many otherglycoproteins, is heterogeneous and presents several circulatingisoforms. Recently, new sensitive immunometric assays measuringintact LH were developed. These assays have been found to underestimateor to be incapable of recognizing LH in some patients. Thisstudy was undertaken to determine the prevalence of such casesand to define their clinical characteristics. We compared threeLH assays using as capture antibodies either a monoclonal antibodythat reacts exclusively with intact LH (ES 600 Boehringer, StratusBaxter) or a monoclonal antibody against the subunit of LH(IMX Abbott). In 17% of 90 patients tested, ES 600 measured> 50% lower LH concentrations when compared with the EVIX.Moreover, in two cases LH was not detectable by ES 600 or Stratus,whereas it was normal with the EVIX. We found another five suchcases and discuss here the clinical data and results of differenthormone measurements in these seven cases of ‘invisibleLH’. Although bioactive LH (mouse Leydig cell assay) wasnormal, the existence of low or even undetectable LH was clinicallyconfusing and led to expensive complementary investigationssuch as gonadotrophin-releasing hormone analogue tests and magneticresonance imaging. The uses and limitations of these assaysare illustrated by different clinical situations in which theresults of the different assays have been misleading.     

黄体生成素及其受体在大鼠肝脏的定位

目的观察黄体生成素(LH)及其受体(LHR)在大鼠肝脏的定位分布,为研究LH是否参与肝代谢功能的调节提供形态学依据。方法应用免疫荧光组织化学双标染色技术,在激光共聚焦扫描显微镜下观察染色结果。结果大鼠肝细胞既呈LH阳性又有LHR阳性,LH和LHR免疫反应阳性物质均分布在大鼠肝细胞的细胞质,细胞核为阴性。不同部位的肝细胞LH及其受体免疫反应强度存在差别。结论 LH及其受体存在于大鼠肝脏细胞,可能对肝脏的功能起调节作用。     

Antihypertensive effect of an immunosuppressive agent, cyclophosphamide, in genetically hypertensive rats of the Lyon strain

The effect of a pharmacological immunosuppression on the development of hypertension and the part played by hormonal secretions of the thymus in this disease were investigated in genetically hypertensive rats (LH) of the Lyon strain. For this purpose, systolic blood pressure (SBP) was measured in cyclophosphamide-treated LH rats and in neonatally thymectomized LH rats receiving thymostimulin, a thymus extract. Cyclophosphamide treatment delayed the onset and attenuated the full development of hypertension in LH rats whereas it had no effect on SBP in normotensive rats (LN). Thymectomized LH rats also exhibited a significantly decreased SBP as compared to sham-operated controls. Thymostimulin treatment slightly increased the SBP of thymectomized LH rats but did not restore it to the level seen in sham-operated animals. These results showed that thymic hormonal secretions did not seem to be involved in the initiation of hypertension. By contrast, the fact that a reduction of hypertension could be obtained either by thymectomy or cyclophosphamide treatment suggested that immune disorders, mediated by thymus-dependent cellular reactions, could be of pathogenic importance in the development of hypertension in LH rats.     

A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus

In response to orthodromic stimulation, granule neurons of the dentate gyrus of the rat hippocampal slice display a late hyperpolarization (LH) with properties which clearly distinguish it from the conventional γ-aminobutyric acid (GABA)-mediated chloride (CI) dependent inhibitory postsynaptic potential (IPSP). The LH is not reduced by antagonists of GABA-mediated CI conductances such as picrotoxin, and it is probably dependent on increased potassium conductance rather than increased CI conductance. The LH can be elicited by orthodromic stimulation which does not elicit a burst of action potentials and, in fact, the LH has been observed following stimulation which did not produce a depolarization detectable at the resting membrane potential. It is suggested that the increased potassium conductance of the LH may be calcium-dependent, or it may be directly elicited by a neurotransmitter.     

Intercellular Communication Within the Rat Anterior Pituitary: XIV Electron Microscopic and Immunohistochemical Study on the Relationship Between the Agranular Cells and GnRH Neurons in the Dorsal Pars Tuberalis of the Pituitary Gland

Although numerous investigators in 1970s to 1980s have reported the distribution of LH‐RH nerve fibers in the median eminence, a few LH‐RH fibers have been shown to be present in the pars tuberalis. The significance of the finding remains to be elucidated, and there are few studies on the distribution of LH‐RH neurons in the pars tuberalis, especially in the dorsal pars tuberalis (DPT). Adult male Wistar‐Imamichi rats were separated into two groups: one for electron microscopy and the other for immunohistochemistry to observe LH‐RH and neurofilaments. Pituitary glands attached to the brain were fixed by perfusion, and the sections were prepared parallel to the sagittal plane. The typical glandular structure of the pars tuberalis was evident beneath the bottom floor of the third ventricle, and the thick glandular structure was present in the foremost region. Closer to the anterior lobe, the glandular structure changed to be a thin layer, and it was again observed at the posterior portion. Then the pituitary stalk was surrounded with the dorsal, lateral, and ventral pars tuberalis. LH‐RH and neurofilaments fibers were noted in the bottom floor, and some of them vertically descended to the gland. Adjacent to the glandular folliculostellate cells in the pars tuberalis, Herring bodies with numerous dense granules invading into the gland were present between the pituitary stalk and DPT. It was postulated that the “message” carried by LH‐RH might have been transmitted to the cells in the DPT to aid in the modulation of LH release. Anat Rec, 290:1388–1398, 2007. © 2007 Wiley‐Liss, Inc.     

Morphological evidence for the 'implantation window' in human luminal endometrium

Endometrial tissue was taken from 21 normal fertile women (aged 18-40 years) between 4 and 13 days after the luteinizing hormone (LH) surge. Systematic random samples of luminal epithelium were taken for both light and electron microscopy and examined morphometrically. Throughout the luteal phase there were remarkably few changes in the volume fraction of nucleus, mitochondria, rough endoplasmic reticulum and 'vesicular system' to cell. Nuclear profile dimensions and cell height also did not change over time. Cell and organelle volume (estimated as volume weighted mean volume) did not change significantly, but showed numerically smallest values on day LH + 13. However the ratio of desmosomes to whole cell and both arithmetic mean thickness and harmonic mean thickness of basement membrane were minimal at the time when implantation would be most likely to occur, i.e. approximately 6 days after the LH peak. Therefore it appears that while some morphometric parameters in human luminal epithelial cells change little during the luteal phase, specific cellular changes occur to the basement membrane and desmosomes which may facilitate embryo implantation. These changes occurred around day LH+ 6 and may be a morphological representation of the 'implantation window'.     

Lateral hypothalamic stimulation can augment or attenuate nucleus gigantocellularis escape: evidence for appetite-associated aversion amelioration

Carr and Coons (1982a, 1982b) found that lateral hypothalamic (LH) stimulation ameliorates the aversiveness of stimulation of pain-implicated nucleus gigantocellularis (NGC), but this finding disagrees with other findings. To resolve this disagreement, we tested whether amelioration is differentially associated with the ability of LH stimulation to support self-stimulation (SS), to support responding to escape LH stimulation (LH escape), or to elicit stimulation-bound feeding (SBF). LH stimulation not yielding SBF always increased responding to escape from NGC stimulation (NGC escape) and was reward-escape in nature in supporting LH escape as well as SS. By contrast, LH stimulation yielding SBF always reduced NGC escape and was purely rewarding in that it only supported SS and never LH escape. In an additional experiment, the anxiolytic diazepam augmented the ability of LH stimulation yielding SBF to reduce NGC escape.