乳洁安胶囊对乳腺增生大鼠激素水平的影响

目的：探讨乳洁安胶囊对乳腺增生大鼠血清中雌二醇（B）、孕酮（P）、催乳素（PRL）的影响。方法：应用腹腔注射苯甲酸雌二醇复制大鼠乳腺增生模型，同时应用药物治疗。实验30d后处死，心脏采血，放免法检测血清中E2、P、PRL的含量。同时取乳腺作组织切片观察。结果：模型组大鼠乳腺增生明显，E2、PRL含量较正常组显著升高，而灌服乳洁安胶囊的大鼠均能不同程度抑制乳腺组织增生，和模型组相比，E2、PRL含量明显降低。结论：乳洁安胶囊有降低乳腺增生大鼠E2、PRL水平，抑制乳腺增生，调节内分泌激素水平的作用。     

溴隐亭治疗垂体催乳素大腺瘤

目的 :探讨单纯溴隐亭治疗垂体催乳素大腺瘤的疗效。方法 :垂体催乳素大腺瘤 2 3例 ,用溴隐亭 7.5～ 10mg·d-1,口服 ,肿瘤愈大 ,催乳素 (PRL)水平愈高 ,则用药剂量愈大。当肿瘤缩小至直径 <1cm、PRL <10 0 μg·L-1时减至 2 .5～5mg·d-1。结果 :2 3例服药 1个月时PRL下降 (6 7± 15 ) %。服药 6个月肿瘤直径缩小 0 .4～ 0 .9cm。 12个月时 2 1例缩小0 .6～ 1.3cm ,2例肿瘤消失。 3年时复查 15例 ,有 11例肿瘤直径仅为 0 .5～ 0 .7cm ,其中 1例伴囊性变 ;3例肿瘤消失 (含上述2例 ) ;1例空蝶鞍。服药 6～ 14周停止溢乳 ,5～ 8周月经恢复。结论 :单纯溴隐亭治疗可使垂体PRL大腺瘤缩小或消失 ,且能恢复病人的生殖内分泌功能。     

利培酮对首发精神分裂症患者的疗效观察及与血浆催乳素水平的相关性研究

目的探讨非典型抗精神病药利培酮对首发精神分裂症患者血浆催乳素(PRL)水平的影响及其与疗效的关系。方法对30例符合CCMD-Ⅲ诊断标准的首发精神分裂症患者(治疗组) 在治疗前后及30例健康自愿者(对照组)的血浆PRL水平用放射免疫法进行检测。用利培酮治疗12 周,采用阳性和阴性症状量表(PAN SS)在治疗前后分别进行评定。结果患者组治疗前血浆PRL水平低于对照组,差异有统计学意义(P<0．05);治疗组治疗后血浆PRL水平明显高于治疗前(P< 0．01);治疗前、后在PAN SS总分及其因子分上差异均有显著性意义(P<0．05)。治疗后PRL水平较高、治疗前后差异较大或治疗前PRL水平较高者,疗效较好,尤其是阳性症状改善明显。结论利培酮治疗明显增加血浆PRL水平;且治疗前后血浆PRL水平与疗效相关,主要与阳性症状的疗效有关。     

不同剂量溴隐亭对催乳素瘤临床疗效、血清催乳素水平及肿瘤体积的影响

目的:探讨不同剂量溴隐亭治疗催乳素瘤的临床疗效、对血清催乳素(PRL)水平和肿瘤体积的影响及安全性。方法:选取2015年1-12月我院收治的催乳素瘤患者60例为研究对象,按照随机数字表法分为A组和B组,各30例。两组患者均餐中口服甲磺酸溴隐亭片,A组患者首次给药剂量为2.5 mg/d,3 d后增至3.75 mg/d,服用2~3 d后每周增加2.5 mg至血清PRL水平得到控制,剂量恢复至3.75 mg/d。B组患者首次给药剂量为1.25 mg/d,3 d后增至2.5 mg/d,服用2~3 d后每周增加1.25~2.5 mg至血清PRL水平得到控制,剂量恢复至2.5 mg/d。两组患者均连续治疗3个月。观察两组患者的临床疗效、治疗前后的血清PRL水平和肿瘤长径,并记录不良反应发生情况。结果:A组患者临床总有效率(83.33%)较B组(66.67%)高,但差异无统计学意义(P>0.05)。治疗前,两组患者血清PRL水平和各类型肿瘤的长径比较,差异均无统计学意义(P>0.05)。治疗1、2个月,两组患者血清PRL水平均较治疗前明显降低,且A组明显低于B组,差异均有统计学意义(P<0.05);治疗3个月,两组患者血清PRL水平均较治疗前明显降低,但组间比较差异并无统计学意义(P>0.05)。治疗后,两组患者各类型肿瘤的长径均明显减小,A组患者大腺瘤和巨大腺瘤的长径均明显小于B组,差异均有统计学意义(P<0.05);但A组患者的微腺瘤长径与B组比较,差异无统计学意义(P>0.05)。A组患者的不良反应发生率(12例,40.00%)明显高于B组(5例,16.67%),差异有统计学意义(P<0.05)。结论:增大溴隐亭的剂量对催乳素瘤的临床疗效无显著影响,但可缩短患者血清PRL水平恢复正常的时间、缩小肿瘤体积,而其不良反应发生率随剂量增大而增加。     

精神分裂症患者的d-芬氟拉明激发试验与利培酮治疗的关系

目的通过催乳素(PRL)、皮质醇(COR)对d-芬氟拉明(d-FF)激发试验的反应,研究精神分裂症患者的中枢5-HT功能,探讨非典型抗精神病药利培酮的抗精神病作用机制.方法以d-FF为探针,用酶联免疫法测定15例精神分裂症患者利培酮治疗前后血清PRL和COR水平,以阳性和阴性症状量表(PANSS)对患者精神症状进行评估.结果利培酮治疗后PRL基础值显著高于治疗前(P<0.01),COR基础值则显著低于治疗前(P<0.05).经基线校正后的PRL曲线下面积(AUC)和皮质醇AUC比治疗前降低,但无显著性差异(P>0.05).利培酮治疗后患者的精神症状得到全面改善.Spearman相关分析显示,PRL的AUC减分率与思维障碍因子的减分率显著相关(n=15,r=0.533,P<0.05),COR的AUC与阳性症状量表分(n=15,r=0.653,P<0.01)和思维障碍因子分(n=15,r=0.884,P<0.01)显著相关.结论利培酮治疗后PRL,COR对d-FF激发试验反应迟钝.精神分裂症患者于治疗前可能存在中枢5-HT功能亢进.利培酮的抗精神病作用机制与5-HT2a/D2受体双重阻断有关.     

奎硫平与利培酮对女性分裂症患者的血清催乳素影响的对照研究

目的：探讨女性精神分裂症患者采用奎硫平与利培酮治疗过程中,血清催乳素（PRL）的变化。方法：选择符合诊断标准的女性精神分裂症患者64例,随机分为奎硫平组与利培酮组,治疗8周,采用阳性和阴性症状量表（PANSS）在治疗前、治疗第4周和第8周分别评定;在治疗前和治疗第4、8周测定血清PRL浓度。结果：治疗前后两组在PANSS总分上无显著差异（P〉0．05）,治疗前两组血清PRL水平无显著差异（P〉0．05）,奎硫平组治疗后PRL水平变化不明显（P均〉0．05）,利培酮组治疗后PRL水平显著升高（P均〈0．01）。结论：奎硫平不引起明显的PRL升高,而利培酮有较强的致PRL升高的作用。     

乳通颗粒对产后缺乳模型大鼠催乳作用的研究

目的:研究乳通颗粒对产后缺乳模型大鼠的催乳作用。方法:取产仔时间前后相差不超过24h的母鼠,用溴隐亭灌胃复制模型,同时灌胃给予乳通颗粒;第2天开始每天测量母鼠泌乳量和子鼠体质量;第8天处死大鼠并检测其血清催乳素(PRL)水平,观察乳腺的病理组织学变化。结果:乳通颗粒有逐渐提高血清垂体PRL水平的趋势,使母鼠乳腺腺泡数增多、腺导管扩张,增加仔鼠的体质量及母鼠的泌乳量。结论:乳通颗粒能提高产后缺乳模型大鼠的血清PRL水平,畅通泌乳通道,增加泌乳量。     

原发性甲状腺功能减退症血清PRL改变及其对TRH反应

本文检测了40例原发性甲状腺功能减退症血清PRL水平,结果显示甲减组PRL 较正常组升高,但无显著差异.但重型甲减较正常组显著升高(P<0.05)。甲减治疗后较治疗前显著下降(P<0.01)。14例TRH 兴奋试验提示垂体PRL 对TRH 刺激反应增强。     

乳泉冲剂对实验性泌乳不足大鼠泌乳量的影响

目的评价乳泉中剂对实验性泌乳不足大鼠泌乳量的影响.方法取Wistar大鼠,随机分为6组,选用己烯雌酚建立实验性泌乳不足模型.各组母鼠自产后当天起,每日给药一次,连续10d,记录母鼠的泌乳量,用放射免疫法测定母鼠血清催乳素(PRL)水平,并取乳腺活检.结果乳泉冲剂可使母鼠泌乳量明显增多,仔鼠体重增长加速,且母鼠的血清催乳素分泌水平有所提高.结论乳泉冲剂可有效地拮抗己烯雌酚抑制泌乳作用.     

赛庚定治疗利培酮所致高催乳素血症31例

目的 探讨赛庚定（CYP）治疗利培酮所致精神分裂症患者血清催乳素（PRL）升高的疗效及不良反应.方法 选择符合CCMD- 3诊断标准,年龄18～40岁,首次发病住院的精神分裂症患者.入院患者单一服用利培酮,第3周末检测PRL,PRL≥26.8 ng·mL^-1者作为入组对象,共31例男性患者.入组当日即口服CYP 18 mg·d^-1,po,tid,持续2周.服CYP期间利培酮的剂量不变.第5周末检测PRL.实验期间有睡眠障碍者允许口服氯硝地西泮,剂量控制在4 mg·d^-1内,记录不良反应. 结果 31例患者入组时PRL平均为（52.25±17.36 ）ng·mL^-1,治疗后PRL平均为（25.52±5.77 ）ng·mL^-1,差值平均为（26.96±16.90 ）ng·mL^-1, PRL比治疗前有明显的下降（P<0.01）,且无明显的不良反应. 结论 CYP治疗利培酮所致PRL升高安全有效.     

Therapeutic potential of S179D prolactin – from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator

Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review focuses on one such antagonist, S179D prolactin, which was produced by mimicking a natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective growth antagonist, partly because it inhibits signalling from unmodified prolactin and partly because it produces its own intracellular signal. This signal results in cell differentiation, cell-cycle arrest or apoptosis depending on dose, duration of treatment and cellular context. S179D prolactin is also a potent antiangiogenic and initial studies have shown it to be a potent anti-inflammatory agent. In light of these additional modes of action, it is suggested that S179D prolactin should now be more aptly referred to as a selective prolactin receptor modulator.     

Hypothesis: prolactin is tumorigenic to human breast: dispelling the myth that prolactin-induced mammary tumors are rodent-specific

The commonly held assumption that rodent mammary tumors resulting from elevated prolactin are species-specific, or not biologically relevant to humans, is incorrect. Substantial epidemiological, clinical, and biological evidence now exists confirming the role of prolactin in human breast cancer. This evidence is evaluated and the argument presented that the tumorigenic risk from prolactin is therefore not species-specific to rodents but directly applies to humans. Further, as the mechanisms of prolactin-induced mammary tumor promotion and development appear analogous between rodents and humans, mammary tumorigenic findings in rodent carcinogenicity bioassays are both predictive and biologically relevant to the human response. Toxicologists and regulators need to consider this in carcinogenicity risk assessments.     

Human relevance of rodent prolactin-induced non-genotoxic mammary carcinogenesis: prolactin involvement in human breast cancer and significance for toxicology risk assessments

Prolactin-induced mammary carcinogenesis in rodents, particularly rats, is often stated to be of low toxicological relevance to humans. This opinion appears to have developed from a number of lines of cited evidence. Firstly, there had been long experience of use of dopamine antagonists (that increase prolactin) in human medicine and no evidence of an increase in breast cancer incidence or risk had been reported. Secondly, dopamine agonists (that lower prolactin) had been shown to have no effect in human breast cancer treatment. Thirdly, the actions of prolactin were considered different between rodents and humans. However, recent evidence now suggests that prolactin has a major role in human breast cancer, and the similarity of mechanism with the rodent suggests that prolactin-mediated mammary carcinogenesis in rodents could be of much higher toxicological relevance to humans than previously thought. Large epidemiology studies have upgraded a limited database and shown that dopamine antagonists (both antipsychotics and anti-emetics) increase breast cancer risk, that hyperprolactinaemia is consistently associated with human breast cancer growth, development and poor prognosis, and that prolactin is indeed a mitogen in human breast cancer cells that suppresses apoptosis and upregulates BRCA1. It is now clear that initial studies giving dopamine agonists to breast cancer patients had no effect because breast cancer cells also produced prolactin independently of the pituitary, which remained uncontrolled and unrecognized in early clinical studies. The evidence for the role of prolactin in human breast cancer is now strong and consistent, and is discussed and related to the risk assessment of drugs and chemicals. The conclusion is that it is invalid to suggest that prolactin-induced mammary carcinogenesis in rodents is of low relevance to humans because prolactin can induce an adverse response in the mammary tissue of both rodents and humans alike. Drugs and chemicals causing rodent prolactin-induced mammary carcinogenesis may therefore pose a risk to humans via the same mechanism if exposures also increase prolactin secretion in humans.     

Therapeutic potential of S179D prolactin--from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator

Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review focuses on one such antagonist, S179D prolactin, which was produced by mimicking a natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective growth antagonist, partly because it inhibits signalling from unmodified prolactin and partly because it produces its own intracellular signal. This signal results in cell differentiation, cell-cycle arrest or apoptosis depending on dose, duration of treatment and cellular context. S179D prolactin is also a potent antiangiogenic and initial studies have shown it to be a potent anti-inflammatory agent. In light of these additional modes of action, it is suggested that S179D prolactin should now be more aptly referred to as a selective prolactin receptor modulator.     

Hydrogen sulfide-releasing aspirin suppresses NF-κB signaling in estrogen receptor negative breast cancer cells in vitro and in vivo

Hormone-dependent estrogen receptor positive (ER+) breast cancers generally respond well to anti-estrogen therapy. Unfortunately, hormone-independent estrogen receptor negative (ER-) breast cancers are aggressive, respond poorly to current treatments and have a poor prognosis. New approaches and targets are needed for the prevention and treatment of ER- breast cancer. The NF-κB signaling pathway is strongly implicated in ER- tumor genesis, constituting a possible target for treatment. Hydrogen sulfide-releasing aspirin (HS-ASA), a novel and safer derivative of aspirin, has shown promise as an anti-cancer agent. We examined the growth inhibitory effect of HS-ASA via alterations in cell proliferation, cell cycle phase transitions, and apoptosis, using MDA-MB-231 cells as a model of triple negative breast cancer. Tumor xenografts in mice, representing human ER- breast cancer, were evaluated for reduction in tumor size, followed by immunohistochemical analysis for proliferation, apoptosis and expression of NF-κB. HS-ASA suppressed the growth of MDA-MB-231 cells by induction of G(0)/G(1) arrest and apoptosis, down-regulation of NF-κB, reduction of thioredoxin reductase activity, and increased levels reactive oxygen species. Tumor xenografts in mice, were significantly reduced in volume and mass by HS-ASA treatment. The decrease in tumor mass was associated with inhibition of cell proliferation, induction of apoptosis and decrease in NF-κB levels in vivo. HS-ASA has anti-cancer potential against ER- breast cancer and merits further study.     

雄激素受体有望成为乳腺癌中新的生物标志物

生物标志物可用于靶向治疗的诊断、预后和预测。雌激素受体（ER）和人类表皮生长因子-2(HER-2)已经成为指导乳腺癌治疗的标准生物标志物。雄激素受体（AR）是一种属于核受体超家族中的类固醇受体，与前列腺癌的发展有关。越来越多的证据表明AR在乳腺癌中起着重要的作用，AR被认为是乳腺癌中有用的生物标志物。现有的生存分析表明，AR在ER+乳腺癌中起到肿瘤抑制作用，是一种有利的预后标志物，而AR在ER-乳腺癌中起肿瘤启动子作用，包括在HER-2阳性型和三阴性乳腺癌（TNBC），是一种不良预后因素。AR还被证明可以预测ER+乳腺癌对辅助激素治疗和TNBC中新辅助化疗的反应潜力。然而，也有相关研究得出与以上相互矛盾的结果，这可能是肿瘤和AR阳性评分方法之间的内在差异导致的。有人建议应用AR表达状态来指导不同乳腺癌亚型的治疗。在未来，AR将成为乳腺癌的可行生物标志物，在乳腺癌中使用AR拮抗剂的临床试验是活跃的，单独靶向AR或其他治疗剂为乳腺癌的现有疗法提供了替代方案。因此，如果要使用AR靶向治疗，AR表达将是必要的。     

吗氯贝胺源性雄鼠乳腺发育症(英文)

目的:研究吗氯贝胺的乳腺毒性及其可能机制.方法:用组织病理学方法判断吗氯贝胺对乳腺的影响,用免疫荧光的方法检测雄激素、雌激素和催乳素的血清浓度,并用免疫组织化学方法半定量测定相关受体的变化.结果:180 d时对照组、60、240、600 mg/kg给药组分别有0、5、5、7只大鼠乳腺发育,30 d恢复期后仅600mg/kg组有1只大鼠乳腺发育.血清催乳素的浓度随着给药剂量的升高而下降,乳腺组织催乳素受体上调.结论:长期服用吗氯贝胺可引起可逆性雄性大鼠乳腺发育,异常发育的机制可能与催乳素受体上调有关.     

氟维司群治疗乳腺癌的若干问题

氟维司群是一种新型甾体雌激素受体拮抗药,可在细胞水平下调雌激素受体和孕激素受体数量,且无激动效应。氟维司群对激素受体阳性的乳腺癌疗效确切,耐受性好,是一种新的内分泌治疗药物。本文回顾氟维司群治疗乳腺癌的临床研究进展,讨论若干临床应用关键问题。     

Rat hepatic prolactin receptor: pubertal exposure to sex steroids alters responsivity to testosterone

Administration of testosterone enanthate to adult female rats lowered the level of hepatic prolactin receptor. Pubertal exposure of intact female rats to testosterone enanthate at the dose used did not affect the level of hepatic prolactin receptor in adults. However, the responsivity of such treated rats to testosterone challenge in adulthood was enhanced. Prepubertal ovariectomy of female rats lowered the level of hepatic prolactin receptor in adulthood. Exposure of the ovariectomized rats during puberty to mestranol (ethynylestradiol 3-methyl ether) at the dose used did not restore the normal adult female rat's level of hepatic prolactin receptor. However, they did become more resistant to subsequent testosterone challenge in adulthood. Exposure of prepubescent ovariectomized rats to testosterone enanthate during puberty reduced the already diminished level of hepatic prolactin receptor further. In addition, these rats were rendered more responsive to testosterone challenge in adulthood.