促性腺激素释放激素类似物在妇科的应用研究进展

促性腺激素释放激素(GnRH)由下丘脑分泌,刺激或抑制垂体促性腺激素的分泌,有相当的活性潜能。在治疗妇科肿瘤、子宫内膜异位症、特发性真性性早熟以及辅助生殖技术中广泛应用,本文对其在妇科的应用现状进行综述。     

长效促性腺激素释放激素类似物治疗性早熟患儿的护理

性早熟指女孩 8岁、男孩 9岁以前呈现出性发育征象。近年来有增多趋势 ,且女孩多于男孩。以往多采用孕酮类药物治疗 ,效果不理想[1] 。我科于1998年 6月至 2 0 0 0年 7月采用长效促性腺激素释放激素类似物 (ＧｎＲＨａ)治疗性早熟女性患儿 9例 ,取得明显效果。报告如下。1　临床资料1.1　一般资料9例女性患儿 ,年龄 6～ 9岁。 1～ 7 5岁 (平均4 9岁 )出现性发育征象 ,表现为早期乳房发育 ,继之出现阴毛、腋毛、卵巢发育 ,随之出现月经。平均身高 12 7 4ｃｍ ;乳房发育按Ｔａｎｎｅｒ法分期[2 ] Ｂ2 期4例 ,Ｂ3期 5例 ;骨龄平均为 9 0岁 ;盆…     

不同促性腺激素释放激素类似物对垂体反应性的作用

促性腺激素释放激素类似物分为激动剂与拮抗剂,在辅助生殖治疗中,主要用于抑制黄体生成素(LH)峰,预防卵泡早排,但两者对垂体反应性产生不同的作用。本文旨在讨论不同促性腺激素释放激素类似物对垂体反应性的影响,以及垂体外效应。     

我们需要更多地认识促性腺激素释放激素

1949年Green和Harris首先建立了“神经(下丘脑)-内分泌(腺垂体)”化学递质系统的学说。下丘脑神经核分泌的促性腺激素释放激素(GnRH)以及一组氨基酸、神经肽、生长因子和癌基因等化学信使,通过内分泌、旁分泌、神经内分泌、自分泌和胞内分泌等机制,作用于垂体和全身多种靶组织和靶细胞,产生了哺乳类和人类丰富和复杂的生殖内分泌功能。神经内分泌节律是脑腺体功能的关键指标,下丘脑GnRH脉冲式释放的特性决定了垂体促性腺激素的节律性分泌,节律性分泌失调导致生殖内分泌功能的紊乱。人类GnRH-受体编码在染色体4q13.2-13.3,大小为18.9 kb…     

促性腺激素释放激素激动剂降调节的个体化与促性腺激素启动日时机选择

促性腺激素释放激素激动剂(GnRH-a)已经广泛地应用于体外受精(IVF)垂体降调节中.GnRH-a分长效和短效两种剂型,长效剂型患者接受性和依从性高,但有卵巢过度抑制倾向,会造成促性腺激素(Gn)用量增加、使用时间延长,因而增加经济负担,而短效者可接受性和依从性较差.两者临床效果无显著差异.临床上常用的GnRH-a降调节方案有长、超长、短、超短等方案,各种方案的临床效果总体上并无显著差异但各有优缺点,通常卵巢功能减退的患者建议给予短方案,甚至超短方案,而卵巢储备功能正常患者常用长方案.超长方案对于合并子宫内膜异位症或多囊卵巢综合征患者等能提高临床妊娠率.降调标准存在争议,因此文献报道对于Gn的启动时间亦有不同,需要根据患者个体及不同的降调节方案而定.适当延迟启动时间可能改善卵母细胞的质量和内膜接受性,从而提高临床妊娠率,而且适当推迟Gn启动时间对于减少Gn的用量,降低患者的经济负担也是十分有益的.     

促性腺激素释放激素抑制剂与促性腺激素释放激素激动剂用于IVF-ET中正常反应患者的系统性评价及Meta分析

目的系统性评价促性腺激素释放激素拮抗剂(GnRH-ant)与促性腺激素释放激素激动剂(GnRH-a)长方案用于体外受精-胚胎移植(IVF-ET)中正常反应患者促排卵治疗的有效性及安全性。方法计算机检索6种数据库,时间截止至2014年12月底。纳入GnRH-ant与GnRH-a用于卵巢正常反应患者治疗的随机对照试验(RCT),采用Revman5.1软件进行Meta分析。结果 24篇RCT符合纳入标准。刺激天数(MD:-0.70,95%CI:-1.08~-0.32)、Gn用量(MD:-2.94,95%CI:-4.9~-0.97)、HCG日E2值(MD:-353.75,95%CI:-530.60~-176.90)、获卵数(MD:-1.32,95%CI:-2.00~-0.64)、临床妊娠率(OR:0.87,95%CI:0.75~1.00)、OHSS率(OR:0.57,95%CI:0.41~0.79)GnRH-ant组显著低于GnRH-a长方案组(P0.05),但是HCG日子宫内膜厚度(MD:-0.07,95%CI:-0.25~0.12)、持续妊娠率(OR:0.88,95%CI:0.75~1.03)、活产率(OR:0.90,95%CI:0.70~1.17)、流产率(OR:1.18,95%CI:0.86~1.62)、周期取消率(OR:1.10,95%CI:0.89~1.35)两组差异无统计学意义(P0.05)。结论在正常反应患者行IVF-ET治疗中,GnRHant方案较之GnRH-a标准的长方案显著降低卵巢过度刺激综合征(OHSS)发生率,持续妊娠率、活产率相似。     

促性腺激素释放激素拮抗剂方案中废弃胚胎发育潜能及其与妊娠结局的关系

目的探讨促性腺激素释放激素拮抗剂（GnRH—ant）方案中废弃胚胎的发育潜能,及其与妊娠结局之间的关系。方法体外受精／卵胞浆内单精子注射（IVF／ICSI）患者共76例：促性腺激素释放激素激动剂（GnRH—a）长方案47例,为A组,拮抗剂方案29例,为B组。收集D3胚胎移植、冷冻后剩余低质量废弃胚胎共274枚（包括异常受精胚胎）,序贯法囊胚培养（A组有囊胚形成者为A1组,无囊胚形成者为A2组;B组有囊胚形成为B1组,无囊胚形成为B2组）,观察囊胚形成情况及妊娠结局,探讨两者之间的关系。结果两组患者基本情况及周期特点无明显差异;促排卵天数及取卵日内膜厚度A组明显大于B组（P〈0．01）。囊胚形成率A组与B组无明显差异（P〉0．05）;总生化妊娠率A组高于B组（P〈0．05）;总临床妊娠率A组显著高于B组（P〈0．01）;生化及临床妊娠率A1组均高于B1组。A1组生化及临床妊娠率均高于A2组（P〈0．05）,B1、B2组妊娠率无显著差异（P〉O．05）。结论部分废弃胚胎具有一定的发育潜能,小部分能发育至囊胚阶段,与GnRH—a相比,拮抗剂不影响其发育潜能;常规GnRH—a长方案废弃胚胎发育潜能与妊娠结局显著相关;与GnRH—a长方案相比拮抗剂方案妊娠率有下降,可能与胚胎发育潜能关系不大,其原因需进一步研究。     

促性腺激素释放激素拮抗剂在超促排卵中的应用

目的分析在高龄患者的体外受精一胚胎移植周期中应用促性腺激素释放激素拮抗剂（GnRH—ant）方案的临床特征和治疗结局。方法回顾性分析233个GnRH—ant移植周期、50个促性腺激素激动剂（GnRH—a）短方案移植周期和253个GnRH—a长方案移植周期患者的促性腺激素（Gn）用药天数和剂量、获卵数、受精率、卵裂率、优质胚胎率和临床妊娠率等差异。结果与GnRH—a长方案组相比,GnRH—ant方案组和GnRH—a短方案组超促排卵时间相对较短,Gn用量较少,而后两组之间无明显差异。三组之间获卵数、受精率、卵裂率、优质胚胎数和临床妊娠率均无统计学差异（P〉0．05）。结论与GnRH—a长方案组相比,在高龄患者应用GnRH—ant方案能缩短促排卵时间,减少Gn用量,而不影响临床妊娠率。     

绝经后激素治疗和妇科恶性肿瘤的研究进展

绝经后激素治疗(MHT)是围绝经期女性健康管理的有效方案,目前的证据发现MHT不增加或轻度增加绝大部分妇科肿瘤的风险,或者在绝大部分妇科肿瘤治疗后应用并不影响患者的预后。因此在处理绝经症状、改善患者生活质量的情况下,妇产科医师有责任和义务在充分知情同意的情况下对适合的人群考虑和推荐MHT。     

Testosterone effects on luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the mouse

Studies in the mouse have demonstrated for the first time in vivo regulation of gonadotropin-releasing hormone (GnRH) on the minute-to-minute dynamics of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release and the effects of testosterone on this regulation. Intact and castrated mice with different testosterone levels (3-9 ng/mL) were challenged with exogenous GnRH while under general anesthesia to block endogenous GnRH release. Plasma concentrations of LH and FSH were determined by radioimmunoassay from sequential blood samples collected from anesthetized mice with in-dwelling catheters. The release of LH was correlated with the infusion of different doses of GnRH (0.35, 3.5, and 35 ng) in both intact and castrated mice (r = 0.942, approximately 0.999). GnRH-stimulated LH release was significantly lower in intact mice and in castrated mice with high testosterone levels than in castrated mice with low testosterone levels (P < .05). However, GnRH did not induce FSH release except in castrated males with low testosterone levels and at the highest dose of GnRH. The profiles of FSH release in intact mice and castrated mice with the highest testosterone levels were significant lower than the other groups (P < .05). In conclusion, release of LH, but not FSH, was correlated with increasing dosages of GnRH (r = 0.970), and testosterone significantly suppressed GnRH-stimulated LH release in the mouse (P < .05).     

Cervical sympathectomy affects gonadotropin-releasing hormone,luteinizing hormone and testosterone in male rats

To examine the effects of bilateral cervical sympathectomy on the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone (TS), 24 male rats were divided into four groups: control (C), light (L), sympathectomy (S), and light-sympathectomy (LS) groups. The C and S groups were kept under a 12-h light-dark cycle and the L and LS groups were kept under continuous light for 2 weeks. After 2 weeks, blood was collected and the rats were perfused with a fixative. GnRH neurons in the hypothalamus were stained immunohistochemically, and serum LH and TS levels were measured by radioimmunoassay. Although the difference in the number of GnRH neurons between the C and S groups was not significant, the L group was significantly lower than the C or LS groups. The serum LH and TS levels in the L group were higher than in the other groups. The present results suggest that continuous light increases GnRH secretion in the hypothalamus, followed by increased secretions of LH in the pituitary and TS in the testes, and bilateral cervical sympathectomy under continuous light inhibits these hormonal changes. However, a normal circadian rhythm does not affect gonadotropin secretion. Therefore, long-term and repeated stellate ganglion block may inhibit the increases of GnRH, LH, and TS secretions induced by continuous light.     

垂体激素和激素替代治疗对骨代谢调控的研究进展

既往研究多认为垂体分泌的激素通过其靶内分泌腺对骨代谢进行间接调控。但近年来,越来越多的研究发现垂体激素如生长激素、促甲状腺素、促性腺素、促肾上腺皮质素以及催产素等对骨代谢具有直接调节作用,这些激素通过作用于相应的受体,激活不同的信号通路,直接作用于成骨细胞、破骨细胞,从而发挥生物学效应,影响骨量及骨质疏松性骨折的发生率。垂体功能低下患者长期使用生长激素、糖皮质激素、性激素、甲状腺素等替代治疗亦对骨代谢有着不同的调控作用。它们也是直接与成骨或破骨细胞膜上相应的受体结合,通过基因或非基因效应,从而对骨量进行调节。本文综述了垂体激素对骨骼的直接作用及激素长期替代治疗对骨代谢的调控,旨在为疾病的早期诊断、精准个体化治疗提供一些思路。     

Simplified gonadotropin-releasing hormone (GnRH) stimulation test

Provocative gonadotropin-releasing hormone (GnRH) stimulation testing indirectly assesses testicular function with more sensitivity than determination of basal gonadotropin levels alone. Unfortunately, the drawbacks of multiple blood sampling and high cost have limited the clinical usefulness of this test. We herein present a simplified, two-point, thirty-minute GnRH stimulation test. Statistical analysis of data from 55 men with normal baseline gonadotropin levels, reveal that this simplified test is just as accurate as the traditional test (p less than 0.0001) without the latter's attendant difficulties. In addition, we found that normal basal gonadotropin levels had little correlation to the actual responses obtained from GnRH stimulation testing (r = 0.20 and r = 0.39 for luteinizing hormone and follicle-stimulating hormone, respectively).     

Insulin-like growth factor-1 is associated with regulation of the luteinizing hormone production in men receiving androgen deprivation therapy with gonadotropin-releasing hormone analogues for localized prostate cancer

BackgroundLuteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear.MethodsSeventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay).ResultsNo correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearman's correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 ± 6 nmol/L) compared with that at the baseline (19 ± 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 ± 2.3 vs. 0.9 ± 0.9 μg/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels.ConclusionsDuring ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer.     

甲状旁腺素在骨质疏松症及骨科领域应用的研究进展

骨质疏松症(osteoporosis, OP)是一种以骨量低下、骨微结构损坏而导致骨脆性增加、易发生骨折为特征的全身性骨病。骨质疏松症所致的骨折严重影响患者的健康和生活质量,并对社会经济造成沉重的负担。目前骨质疏松症的治疗手段主要是以双膦酸盐类为主的抗骨吸收类药物。这类药物抑制骨吸收,但无法新生成骨组织。以重组人甲状旁腺素（1-34)[PTH(1-34)]为代表的促骨形成类药物作用于成骨细胞,通过刺激骨形成发挥作用,为治疗骨质疏松症提供了新的选择。多项临床研究证明PTH(1-34)可增加骨密度并改善骨结构,长期应用可降低骨质疏松症患者椎体和非椎体骨折发生率。PTH (1-34)巳在中国获批用于治疗有骨折高发风险的绝经后妇女骨质疏松症。骨质疏松症不仅增加了患者发生骨折的风险,也使得骨折愈合更加困难。由于PTH(1-34)特殊的成骨作用机制,近年来其在治疗骨折不愈合和脊柱融合等骨科领域的应用也日益受到重视,并且巳经有一些成功的个案报道。本文回顾了近年来国内外关于PTH( 1-34)在骨质疏松症和骨科领域的临床研究的进展,以期为临床实践提供参考。     

Immunohistochemical demonstration of gonadotropin-releasing hormone receptors in prostate carcinoma

The antiandrogen and gonadotropin-releasing hormone (Gn-RH) analogue treatment of prostate carcinoma is based on decreased proliferative and increased apoptotic activity of tumor cells, induced by androgen ablation. Gn-RH analogues decrease the serum level of androgens by breaking the pituitary-gonadal axis, but increasing evidence points to the direct effect of Gn-RH analogues on tumor cells. Immunohistochemical demonstration of Gn-RH receptors recently became possible. Cryostat and paraffin sections of prostate biopsy samples of 10 untreated patients with prostate carcinoma (T2−T3, Gleason score 5−8) were investigated for Gn-RH receptors (Gn-RHR) and androgen receptors, respectively, using the immunoperoxidase method. Membrane bound, focal Gn-RHR positivity was found in 5 samples. Nuclear androgen receptor positivity appeared in 7 samples. No correlation between Gn-RHR and androgen receptor positivity was found, neither receptor status and tumor-nodes-metastasis stage nor Gleason score could be related to each other. Correlation between Gn-RHR positivity and response to luteinizing hormone-releasing hormone analogue treatment will be investigated further.     

Effects of gonadotropin-releasing hormone analogs on cis-platinum-induced spermatogenic damage

In order to test the hypothesis that pretreatment with gonadotropin-releasing hormone (GnRH) analogs might ameliorate cytotoxic drug-induced testicular damage, mature male Wistar rats were pretreated for 2 weeks with a GnRH superactive agonist or a pure GnRH antagonist prior to, and for 1 week after, a 5 mg/kg intraperitoneal dose of cis-platinum. Despite inhibition of testicular function by both GnRH analogs prior to cis-platinum administration, there was no evidence of protection or enhanced recovery of spermatogenesis at 6 and 12 weeks after cis-platinum treatment, and spermatogenesis was significantly further depressed at both time-points by both GnRH agonist and antagonist pretreatment. This suggests that pretreatment with GnRH analogs in the rat does not protect spermatogenesis from cis-platinum-induced testicular damage within up to two spermatogenic cycles and that hypogonadism at the time of cytotoxic drug treatments may aggravate testicular damage.     

卵母细胞代谢及其调节

卵母细胞发育与成熟过程依赖大量ATP,因此物质代谢旺盛。卵母细胞以葡萄糖和/或其中间产物丙酮酸为底物,在线粒体内氧化磷酸化,产生大量ATP,是卵母细胞最主要的供能形式。但是,卵母细胞糖代谢模式有种属特异性差异。同时,卵母细胞也存在脂肪酸和氨基酸的代谢。除提供能量外,这些代谢产物在细胞信号传导、渗透压调节等方面也有重要作用。卵母细胞代谢的精确调控受多方面因素的影响如卵母细胞胞内、胞间、胞外的调控等。研究卵母细胞代谢及其机制,对探寻改善卵母细胞质量、提高卵母细胞体外成熟效能具有重要的意义。