特发性中枢性性早熟女童ERα基因Pvu Ⅱ和Xba Ⅰ多态性分析

目的 探讨雌激素受体α(Estrogen receptor,ERα)基因PvuⅡ和Xba Ⅰ多态性与特发性中枢性性早熟(Idiopathic central precocious puberty,ICPP)女童发病的关系.方法 选取特发性中枢性性早熟女童100例,同时选择体检健康女童100例为对照组,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法检测两组女童ERα基因内切酶PvuⅡ和Xba Ⅰ限制性片段长度多态性,比较分析两组Pvu Ⅱ和Xba Ⅰ基因型及等位基因分布频率.结果 ①ERα基因PvuⅡ基因型PP、Pp、PP频率,XbaⅠ基因型XX、Xx、xx频率分别与对照组相比,差异均有统计学意义(x2=9.023,P=0.011;x2=11.740,P=0.003);②携带Pvu Ⅱ的P等位基因发生ICPP的相对风险是p的1.750倍(95％CI:1.152～ 2.659,P＜0.05);携带XbaⅠ的X等位基因发生ICPP的相对风险是x的2.061倍(95％CI:1.351～ 3.145,P＜0.05).结论 在ICPP人群中存在雌激素受体α基因Pvu Ⅱ和Xba Ⅰ位点基因多态性,P等位基因和X等位基因可能是特发性中枢性性早熟女童遗传易感性基因,Pp基因型或Xx基因型相对易于患病.     

肥胖对中枢性性早熟女童GnRH激发试验促黄体生成素峰值及相关激素的影响

目的探讨肥胖对中枢性性早熟女童GnRH激发试验促黄体生成素(LH)峰值及相关激素的影响。方法选取我院2012~2014年完成GnRH激发试验的中枢性性早熟女童333例,根据体重指数(BMI)分为正常体重组(n=123)、超重组(n=108)和肥胖组(n=102),并对3组性发育指标进行比较分析。再分别从各组中随机抽取20例,检测血清瘦素(leptin)、性激素结合蛋白(SHBG)、神经激肽B(neurokini B)和吻素(kisspeptin)水平,Pearson相关分析分析BMI与各激素水平的相关性。结果各组平均诊断年龄差异无统计学意义,但超重及肥胖组的骨龄显著大于正常体重组(P0.05)。正常体重组血清LH激发峰值、SHBG水平显著高于超重及肥胖组,leptin及neurokini B水平显著低于超重及肥胖组(P0.05)。BMI与GnRH激发试验LH峰值、SHBG水平呈负相关(P0.05),与leptin和neurokini B水平呈正相关(P0.05)。结论在分析性早熟女童GnRH激发试验结果及相关激素水平时需考虑BMI对结果的影响。     

Sex‐ and region‐specific pubertal maturation of the corticotropin‐releasing factor receptor system in the rat

One of the most reliable findings in psychiatry is in the incidence of anxiety and depression. Beginning at puberty, women develop mood disorders twice as often as men. Because corticotropin‐releasing factor (CRF) receptors are implicated, we compared CRF receptor binding in pre‐ and postpubertal rats. In each brain area, CRF receptor binding was sexually dimorphic, but no two areas were alike in the way the sexes differed. In the nucleus accumbens and olfactory tubercle, CRF₁ binding was initially the same in juveniles, but became greater in adult females. In piriform cortex, CRF₁ binding increased in females and decreased in males, again becoming sexually dimorphic. CRF₁ binding in the anterior cingulate was greater in females than in males at both ages. In CA3, CRF₁ binding was greater in males before puberty but decreased during puberty, abolishing the sex difference. CRF₂ binding in the posterior bed nucleus of the stria terminalis was greater in males irrespective of age. In contrast, in each of three subdivisions of the lateral septum, females had greater CRF₂ binding than males as juveniles, or, as juveniles and as adults. CRF₂ binding in the ventromedial hypothalamus was the same in juveniles, but binding levels increased in males, leading to an adult sex difference. Thus, eight CRF receptor‐expressing areas displayed eight distinct sex differences. These results show that sex differences pervade the CRF receptor system in juvenile and adult rats, and the mechanisms that control them are likely to be sex‐, region‐, and subtype‐specific. J. Comp. Neurol. 522:1284–1298, 2014. © 2013 Wiley Periodicals, Inc.     

Relationship between chronic raised intracranial pressure and empty sella presenting hormonal disturbances

The role of intracranial pressure in the development and maintenance of the primary empty sella has been pointed out in the literature previously. The hormonal changes and clinical features have been evaluated in a 30 year-old female patient examined for a convexity meningioma and a 20 year-old patient examined for chronic hydrocephalus caused by cured meningitis. Histories and investigations revealed an empty sella turcica associated with primary amenorrhoea and delayed puberty. The removal of the convexity meningioma resulted in loss of amenorrhoea and a rise in plasma gonadotrophins. The establishment of a ventriculo-peritoneal shunt did not bring about any changes in hormonal values and clinical features except the subjective headache disappeared. The importance of consideration of intracranial causes in patients who have delayed puberty or absence of menstrual history is briefly emphasized in light of the literature. Our data also demonstrated a correlation between an increase in intracranial pressure and a deficiency of hormonal secretion by the hypophysis.     

Periadolescent maturation of the prefrontal cortex is sex‐specific and is disrupted by prenatal stress

The prefrontal cortex (PFC) undergoes dramatic, sex‐specific maturation during adolescence. Adolescence is a vulnerable window for developing mental illnesses that show significant sexual dimorphisms. Gestational stress is associated with increased risk for both schizophrenia, which is more common among men, and cognitive deficits. We have shown that male, but not female, rats exposed to prenatal stress develop postpubertal deficits in cognitive behaviors supported by the prefrontal cortex. Here we tested the hypothesis that repeated variable prenatal stress during the third week of rat gestation disrupts periadolescent development of prefrontal neurons in a sex‐specific fashion. Using Golgi‐Cox stained tissue, we compared dendritic arborization and spine density of prelimbic layer III neurons in prenatally stressed and control animals at juvenile (day 20), prepubertal (day 30), postpubertal (day 56), and adult (day 90) ages (N = 115). Dendritic ramification followed a sex‐specific pattern that was disrupted during adolescence in prenatally stressed males, but not in females. In contrast, the impact of prenatal stress on the female PFC was not evident until adulthood. Prenatal stress also caused reductions in brain and body weights, and the latter effect was more pronounced among males. Additionally, there was a trend toward reduced testosterone levels for adult prenatally stressed males. Our findings indicate that, similarly to humans, the rat PFC undergoes sex‐specific development during adolescence and furthermore that this process is disrupted by prenatal stress. These findings may be relevant to both the development of normal sex differences in cognition as well as differential male–female vulnerability to psychiatric conditions. J. Comp. J. Comp. Neurol. 521:1828–1843, 2013. © 2012 Wiley Periodicals, Inc.     

41例青春期子宫内膜异位症诊疗分析

目的 探讨青春期子宫内膜异位症（endometriosis,EMs） 的临床特征、诊断、治疗及预后。 方法 回顾性分析2008 - 2012 年本院收治的41 例青春期EMs 患者临床资料并进行随访。 结果 19.5% 的患者伴有生殖道畸形,与无畸形组相比,确诊年龄距初潮年龄的平均间隔时间较短（P ＜ 0.01）,分期早（P ＜ 0.05）。41 例患者行腹腔镜下或开腹卵巢囊肿剥除术及病灶清除术,部分行生殖道畸形矫正手术,术后25 例患者接受促性腺激素释放激素激动剂辅助治疗。36 例获得随访病例中,接受药物辅助治疗组患者复发率显著低于单纯手术组（P ＜ 0.05）。 结论 青春期子宫内膜异位症患者临床症状主要表现为痛经、慢性盆腔痛及急性腹痛;合并生殖道畸形患者确诊年龄较小、术中分期较早时,手术是其主要治疗方法,术后使用药物辅助治疗可有效避免复发。     

Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.¹ We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data.We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.     

李赟主任治疗青春期继发性闭经经验抉微

李赟主任从事妇科临床多年,认为肾精不足、脾肾虚弱、肝气郁结、脾虚湿阻皆可致闭经,但继发性闭经的主要病机为肾气不足,肾虚不能化生精血,以致血海空虚,不能按时满溢。临床上李师常治以补肾填精,益气养血之法,以其自拟方“补肾八珍汤”为基础方,随症加减,疗效显著。