Lateral ventricle injection of orexin-A ameliorates central precocious puberty in rat via inhibiting the expression of MEG3

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP. Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin. Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3. Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.     

Girls with Premature Thelarche Younger than 3 Years of Age May Have Stimulated Luteinizing Hormone Greater than 10 IU/L

Objective:Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age.Methods:A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study.Results:On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants.Conclusion:Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.     

曲普瑞林兴奋试验用于评价女性下丘脑-垂体-性腺轴功能研究

目的探讨黄体生成素释放激素(LHRH)类似物(曲普瑞林)兴奋试验在评价女性下丘脑-垂体-性腺轴(HPGA)功能中的价值及安全性。方法 2007年1月至2009年12月在北京协和医院内分泌科进行研究:(1)对30例育龄期女性行曲普瑞林兴奋试验,肌注曲普瑞林100μg后,在0、15、30、45、60、90 min测定血卵泡刺激素(FSH)和黄体生成激素(LH)水平,摸索其变化规律和峰值时间;(2)对79例女性性腺疾病患者行曲普瑞林兴奋试验,并随访直至确诊。分析不同疾病中LH峰值水平和诊断之间的相关性,评价兴奋试验在疾病诊断和治疗中的价值。结果 (1)育龄期女性,LH峰值在肌肉注射曲普瑞林后60～90 min出现。(2)80%的全垂体前叶功能减退症患者(10例)、100%的单纯乳房发育患者(12例)、100%的外源性雌激素导致假性性早熟患者(6例)、100%的低促性腺激素性性腺功能减退症患者(5例)和100%因真性性早熟接受GnRH类似物治疗的患者(11例),LH峰值均<6 U/L;100%真性性早熟患者(16例)和青春发育后(30例)的患者,LH峰值均>6 U/L,其中85%的青春发育后的女性,LH峰值>18 U/L。(3)试验过程中未发现局部和全身不良反应。结论曲普瑞林兴奋试验可用于评价不同生理和病理状态下女性患者的下丘脑-垂体-性腺轴功能,有助于性早熟等疾病的鉴别诊断和疗效评价,且安全性好。LH峰值>6 U/L可作为下丘脑-垂体-性腺轴功能开始启动的判断指标;而LH峰值>18 U/L,可作为性成熟女性下丘脑-垂体-性腺轴功能正常的指标。     

Reproduction in male swamp wallabies (Wallabia bicolor): puberty and the effects of season

This study describes pubertal changes in testes and epididymides and seasonal changes in the adult male reproductive organs and plasma androgen concentrations of the swamp wallaby (Wallabia bicolor). Pre-pubescent males had testes with solid seminiferous cords and spermatogenesis only to the stage of gonocytes. Their epididymides had empty lumina along their entire length. The testes of three males undergoing puberty had some lumen formation and mitotic activity. Their epididymides were similar in appearance to those of adult males but were entirely devoid of any cells within the lumen of the duct. Three other pubescent males showed full lumen formation in the testes and spermatogenesis up to the elongating spermatid stage. Their epididymides were similar in appearance to those of adult males but with no spermatozoa in the duct. However, cells of testicular origin were found in the lumen of the duct in all regions suggesting that testicular fluids and immature germ cells shed into the rete testes flow through the seminiferous tubules into the epididymis before the release of mature testicular spermatozoa. The weights of testes and epididymides of adult males showed no change throughout the year but prostate weight and plasma androgen concentrations varied significantly with season, with maximums in spring and summer and minimums in winter. The volume fraction of Leydig cells and seminiferous tubules was significantly lower in winter than in summer; but, despite this, maturing spermatozoa were found in the testes throughout the year. Females in the area conceived year-round, suggesting that seasonal changes in the male reproductive tract did not prevent at least some males from breeding throughout the year.     

醋酸曲普瑞林联合心理干预治疗特发性中枢性性早熟患儿的疗效观察

摘 要 目的：探讨醋酸曲普瑞林联合心理干预治疗特发性中枢性性早熟患儿的疗效。方法: 40例中枢性性早熟患儿随机分为观察组和对照组,每组20例。对照组给予肌注醋酸曲普瑞林,每28 d 1次;观察组在对照组治疗基础上,增加每28 d 1次的心理干预。观察比较两组患儿治疗1年前后的情绪稳定性、抑郁心理、治疗依从性,以及身高、体质量、生长速度、骨龄（BA）、预测成年身高（PAH）等各项生长指标变化。结果:治疗1年后,观察组患儿的情绪稳定性评分及抑郁心理HAMD评分均显著低于对照组(P＜0.05),用药依从性明显高于对照组(P＜0.05)。观察组患儿的生长速度、PAH均显著高于对照组(P<0.05)。结论:醋酸曲普瑞林联合心理干预治疗特发性中枢性性早熟患儿,可以缓解患儿的抑郁心理、稳定情绪、提高用药依从性,且有效地提高生长速度,显著改善患儿的PAH。     

青春期前特发性矮身材儿童的生长激素应用剂量研究

目的 研究重组人生长激素(rhGH)的不同应用剂量对青春期前特发性矮身材(ISS)儿童的临床治疗疗效。方法 选取2014年3月-2016年6月于郑州市妇幼保健院接受治疗的68例ISS患儿为研究对象,在经郑州市妇幼保健院伦理委员会通过的情况下,将其按照随机数表分成两组,其中34例采用皮下注射rhGH 0.25 mg/(kg·每周)为低剂量组,34例采用皮下注射rhGH 0.40 mg/(kg·每周)为高剂量组,治疗疗程均为14个月,对比两组患儿治疗后生长速度(GV)、身高标准差积分(HtSDS)、骨龄以及不良反应的发生率。结果 研究发现,两组患儿在治疗前后的身高(cm)(107.4±6.85 vs. 126.7±7.15)、GV(7.45±1.09 vs. 11.68±1.37)以及HtSDS(-0.96±0.43 vs. -0.64±0.52)等存在明显差异,差异具有统计学意义(P<0.05),两组患儿的骨龄比较,差异无统计学意义(P>0.05);两组患儿出现注射部位红肿、疼痛的例数比较,差异无统计学意义(P>0.05),均可自行消退。结论 rhGH对治疗ISS有显著效果,高剂量rhGH的治疗效果优于低剂量rhGH。     

夏永良应用“玄府郁闭”理论治疗青春期后痤疮的经验浅析

[目的] 基于“玄府郁闭”理论,探讨夏永良老师治疗湿热郁闭型青春期后痤疮的临床经验。[方法] 通过查阅《黄帝内经》《素问玄机原病式》及后世医药典籍,分析“玄府郁闭”的理论依据,收集整理夏师门诊诊治的湿热郁闭型青春期后痤疮病例,并总结相关治疗经验及用药特色,最后分析典型案例进一步论述夏师临证经验。[结果] 夏师认为,湿热郁火之邪可致玄府闭塞、气津不通而发生痤疮,治疗中应以麻黄连轺赤小豆汤为基础,清里之湿热,开表之玄府,畅其气津,祛其郁阻,则痤疮可消。所举验案,夏师辨为湿热内蕴、经络瘀滞之证,治拟清热利湿、宣郁通络之法,方以麻黄连轺赤小豆汤合升降散、葛根芩连汤加减,辄收佳效。[结论] 夏师治疗湿热郁闭型青春期后痤疮以开通玄府为基础,标本兼顾,并注重食饮有节,起居有常,其临床经验值得学习和借鉴。     

Precocious synapses in 13.5-week fetal holoprosencephalic cortex and cyclopean retina

Background: Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20–31 weeks gestation. Materials and methods: Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, alobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears. Immunocytochemical demonstration of the synaptic vesicle protein synaptophysin was performed in the brain and retina, along with other neuronal markers. Results: Synaptophysin reactivity in the cortical plate was patchy and precocious. Radial glial fibres, demonstrated by vimentin, were oriented parallel to the cortical plate rather than perpendicular, probably because of hydrocephalus. A corpus striatum was not identified, but the poorly formed thalamus exhibited synaptophysin reactivity around many neurones. The cyclopean eye had ocular features of maturational delay including persistent hyaloid artery; ganglion cells were reduced in number, but retinal synaptophysin reactivity was paradoxically precocious. Conclusions: Holoprosencephaly exhibits abnormal patchy synapse distribution in the neocortex and retina; synaptogenesis was precocious, as we previously described in older fetuses. Too soon an onset of synapse formation may promote early epileptic circuitry, leading to severe infantile epilepsies postnatally. The visual system is the last of the special sensory systems to mature, yet in this case showed too early synapse formation. In HPE, cyclopia and in trisomy 13, total absence of external ears has not been reported; it results from faulty craniofacial induction by neural crest.