Kisspeptin/GPR54系统与促性腺轴及青春期发育关系的研究进展

1青春期发育的研究现状 下丘脑合成和分泌的促性腺激素释放激素（gonadotropin-releasing hormone，GnRH）是启动下丘脑-垂体-性腺（hypothalamic-pituitary-gonadal，HPG）轴的一种重要神经激素，以脉冲方式释放至垂体门脉循环，刺激垂体卵泡刺激素（FSH）和黄体生成素（LH）的合成和释放，     

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下丘脑-垂体-性腺轴(HPGA)主宰生殖系统的发育和功能。下丘脑以间歇性脉冲形式分泌促性腺激素释放激素(GnRH),垂体前叶细胞分泌促性腺激素(Gn),即促黄体激素(LH)和促卵泡生成素(FSH),卵巢或睾丸分泌雌二醇或睾酮。上述激素组成了复杂的网络系统,调控着人体性腺、性器官的发育及生殖功能的成熟。青春期前,GnRH分泌少。青春发育(10岁左右)时,GnRH分泌增加,其分泌脉冲和分泌峰值在睡眠时逐渐增加,LH和FSH分泌脉冲峰值亦在夜间增高,以后不随睡眠时间更替并持续增高。下丘脑发育成熟的早晚与遗传因素有关。外界环境因素的干预,包括营养…     

性早熟诊断与治疗的现状和进展

人类生殖系统的发育和功能维持受下丘脑 -垂体 -性腺轴 (ＨＰＧＡ)的控制。下丘脑以间歇性脉冲形式分泌促性腺激素释放激素（ＧｎＲＨ） ,作用于靶细胞膜上的受体 ,刺激垂体前叶分泌促性腺激素（Ｇｎ） ,即促黄体激素（ＬＨ）和促滤泡生成素（ＦＳＨ） ,促进卵巢或睾丸的发育并分泌雌二醇 (Ｅ２)或睾酮。青春期前儿童下丘脑分泌的ＧｎＲＨ量甚少 ,垂体 -性腺轴功能处于甚低水平 ;至１０岁左右 ,ＧｎＲＨ的分泌脉冲和分泌峰值在睡眠时逐渐增加 ,ＬＨ和ＦＳＨ分泌的脉冲峰值亦开始在夜间增高 ,后渐不随睡眠时间更迭并持续增高。此期下丘脑对Ｇ…     

促性腺激素释放激素类似物激发试验尿检法对儿童促性腺激素释放激素类似物疗效的判断价值

目的 探讨促性腺激素释放激素类似物(GnRHa)激发试验时免疫化学发光分析法(ICMA)检测的无创性尿促性腺激素(UGn)可否用于儿童GnRHa的疗效判断.方法 患儿23例(男4例,女19例).中枢性性早熟17例(均为女童),予GnRHa治疗.青春期预测终身高矮小6例(男4例,女2例),予GnRHa联合生长激素治疗.在治疗前和治疗3个月均行GnRHa激发试验,留激发试验0～3.5 h尿,其中18例留取了激发试验前1d同一时段的日间自发性尿,应用ICMA检测促黄体生成素(LH)和卵泡刺激素(FSH).结果 1.治疗前后GnRHa激发试验时UGn显著性检验:治疗前后的尿促黄体生成素(ULH)水平分别为(1.27±1.63) IU和(0.07±0.06) IU,尿卵泡刺激素(UFSH)水平分别为(6.38±3.85)IU和(0.54±0.30) IU.2.GnRHa激发试验时血清Gn峰值和UGn对GnRHa疗效评估:当血清LH峰值(PLH)和FSH峰值(PFSH)分别≤2.30IU·L-1和2.39 IU·L-时,其判断疗效的灵敏度分别为95.45％和100％,特异度均为100％；当ULH水平和UFSH水平分别≤0.083 IU和1.089 IU时,其灵敏度分别为90.91％和100％,特异度均为100％.3.GnRHa激发试验时血清Gn和UGn分别与其激发试验前的比值对GnRHa疗效评估:当血清PLH/日间自发性血清LH、血清PFSH/日间自发性血清FSH分别≤5.40和2.16时,其灵敏度和特异度均为100％；当其激发试验时ULH水平/日间自发性ULH水平、激发试验时UFSH水平/日间自发性UFSH水平分别≤6.076和2.480时,其灵敏度和特异度也均达100％.结论 GnRHa激发试验时ICMA检测的无创性3.5 h UGn水平、激发试验时3.5 h UGn水平/日间自发性UGn水平指标可能对儿童GnRHa疗效具有判断价值,其中UFSH水平及其与日间自发性UFSH水平比值指标价值可能更大.     

夜尿促性腺激素与儿童下丘脑-垂体-性腺轴启动的关系

目的探讨夜尿促性腺激素与儿童下丘脑-垂体-性腺轴(HPGA)启动的关系。方法生长或发育异常患儿68例。男20例,女48例。性早熟42例(其中伴垂体微腺瘤3例),预测终身高矮小11例,生长激素缺乏症6例,特发性矮小3例,男性乳房女性化2例,颅咽管瘤(术后放疗)、超重伴垂体微腺瘤、代谢性骨病和Turner综合征各1例。均住院行促性腺激素释放激素类似物激发试验。激发试验前留取其夜间12h尿。应用免疫化学发光法检测其血清和尿促黄体生成素(LH)和卵泡刺激素(FSH),且夜尿LH(NULH)和夜尿FSH(NUFSH)用肌酐(Cr)校正。激发试验0min血液作为血自发性LH(SLH)和血自发性FSH(SFSH)标本。结果NULH/Cr与血LH峰值的相关系数为0.584,P<0.001;NUFSH/Cr与血FSH峰值的相关系数为0.206,P=0.092。NULH/Cr、NUFSH/Cr、NULH/NUFSH、SLH、SFSH和SLH/SFSH判断HPGA启动的受试者工作特性曲线下面积分别为0.790、0.665、0.713、0.762、0.799和0.634。当NULH/Cr≥68.8064IU.mol-1时,判断HPG...     

能量代谢因子促生长激素释放肽与青春期启动

促生长激素释放肽与机体摄食和能量代谢的调节有关,同时能够调节机体与性激素分泌相关的促性腺激素类物质释放,是连接能量代谢与下丘脑-垂体-性腺轴的桥梁因子.生殖系统功能的启动与成熟与机体的营养状态密切相关,儿童青春期的启动需要一定的体脂储备,肥胖儿童青春期易提前启动,促生长激素释放肽可能是传递机体营养状态的信号因子之一,可能在青春期的启动中发挥一定的作用.     

曲普瑞林激发试验对女童曲普瑞林疗效的评估

目的 探讨曲普瑞林(促性腺激素释放激素类似物)激发试验在女童曲普瑞林疗效评估中的价值.方法 女童31例.其中中枢性性早熟26/31例,采用曲普瑞林(商品名达菲林)治疗；青春期预测终身高矮小4/31例和青春期特发性矮小1/31例,均予以曲普瑞林联合生长激素治疗.曲普瑞林治疗前及治疗3个月(注射下一次曲普瑞林前)均行曲普瑞林激发试验(达必佳,晨起8:30,每次0.1 mg,皮下注射),注射曲普瑞林0 min血样作为日间自发性促性腺激素(Gn)标本,另采集注射前夜00:00血样作为夜间自发Gn标本.应用免疫化学发光分析法(ICMA)检测促黄体生成素(LH)和卵泡刺激素(FSH)水平.结果 30/31例女童曲普瑞林治疗有效,治疗后LH峰值(PLH)最大值为1.68 IU·L-1:1/31例疗效不佳,治疗后PLH为3.81IU·L-1.在30例治疗有效患儿中,曲普瑞林治疗后PLH[(0.98±0.39) IU·L-1]明显低于其治疗前[(26.11±16.59) IU·L-1](P=0.000),治疗后FSH峰值(PFSH)[(1.65 ±0.85) IU·L-1]也明显低于其治疗前[(17.78±7.09) IU·L-1](P=0.000),治疗前后PLH和PFSH均无重叠性；治疗后日间自发性LH[(0.47±0.25)IU·L-1]低于其治疗前[(1.88±3.24) IU·L-1](P=0.000),日间自发性FSH[(1.12±0.56) IU·L-1]也低于其治疗前[(5.28±4.49) IU·L-1](P=0.000).22/30例治疗后夜间自发性LH[(0.48±0.27) IU·L-1]低于其治疗前[(4.55±4.54) IU·L-1](P=0.000),夜间自发性FSH[(1.16 ±0.47)IU·L-1]也低于其治疗前[(5.34±2.63)IU·L-1](P=0.000).结论 单次自发性Gn检测对生长或发育异常女童曲普瑞林疗效具有初步评估价值,曲普瑞林激发试验(ICMA检测法)可作为女童曲普瑞林疗效评估的可靠检测方法.     

急性白血病化疗对垂体、性腺、甲状腺激素的影响

目的评价儿童急性白血病(AL)及联合化疗对其垂体、性腺、甲状腺激素的影响。方法测定37例(男23例,女14例)AL患儿化疗前后和20例对照组血清促卵泡激素(FSH)、黄体生成素(LH)、睾酮(T)、雌二醇(E2)、催乳素(PRL)、生长激素(GH)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平。结果AL患儿FSH、LH、T、E2、GH、FT4、TSH水平化疗前后及对照组各组差异无显著意义(P>0.05),PRL水平治疗前高于对照组(P<0.01),男童PRL水平治疗前后比较差异有显著意义(P<0.01)。FT3治疗前低于对照组(P<0.001),治疗后趋于正常(P>0.05)。结论AL本身及联合化疗对患儿垂体-性腺轴功能及GH水平无明显影响。AL本身可使PRL水平升高,而化疗药物可抑制男童PRL的分泌。联合化疗对甲状腺功能无影响,FT3水平对判断AL患儿病情变化、疗效及预后有一定参考意义。     

血清促性腺激素基础值在性早熟女童诊断中的价值

目的：探讨血清促性腺激素基础值在性早熟女童诊断中的价值。方法：以促性腺激素释放激素（GnRH）激发试验结果作为性早熟诊断的金标准,将77例性早熟女童分为中枢性性早熟（CPP,n=45）和单纯性乳房早发育（IPT,n=32）两组,分别比较两组黄体生成素（LH）、卵泡刺激素（FSH）基础值及LH/FSH比值的差异;并采用受试者工作特征（ROC）曲线分析LH、FSH基础值及LH/FSH比值诊断性早熟的准确性。结果：CPP组患儿血清基础LH、FSH水平及LH/FSH比值均高于IPT组（P<0.01）;两组患儿LH基础值与GnRH激发试验中LH峰值存在正相关;LH、FSH和LH/FSH比值诊断CPP的曲线下面积（AUC）进行比较,AUCLH大于AUCFSH和AUCLH/FSH（均P＜0.05）,而AUCFSH和AUCLH/FSH之间比较差异无统计学意义。当血清LH基础值为0.62 IU/L时,敏感度为0.778,特异度为0.906,Youden指数最大（0.684）;当切割值为1.5 IU/L时,诊断敏感度下降为0.311,但特异度为1.0。结论：血清LH基础值诊断CPP的价值优于LH/FSH比值及FSH基础值,可用于性早熟女童门诊的初步诊断,但存在一定的误诊和漏诊率;对于LH基础值大于1.5 IU/L的患儿,结合临床表现可明确诊断,无需另行GnRH激发试验。     

内分泌系统疾病

311 ,72326特发性垂体性生长激素缺乏症下丘脑一垂体一靶腺轴完整性探讨/沈永年一//临床儿科杂志一1996,14(6)一363一365 对25例典型的垂体性GH缺乏症进行下丘脑一垂体一甲状腺、肾上腺和性腺轴功能评价。经TRH、ITT和LHRH激发试验结果表明:单一GH缺乏症3例,占12%,多种垂体激素缺乏22例,占88%。其’中垂体TSH、ACTH、F’SH或LH储备和分泌功能低下分别’为一4(56%)、3(12%)和20(8(〕%)例。伴随TSH和FSH/LH同时受累n例(44 .0%),TSH和ACTH同时受累2例(8%),TSH、ACTH和FSH/LH同时受累1例(4%)。了解垂体其它激素不足,及时…     

Pituitary-gonadal axis in male undermasculinisation

AIMS—To study the value of assessing serum concentrations of luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in patients with male undermasculinisation not caused by androgen insensitivity.
METHODS—A retrospective study of a register of cases of male undermasculinisation (20 with abnormal testes, eight with 5α-reductase deficiency, three with testosterone biosynthetic defects, seven with Drash syndrome, and 210undiagnosed).
RESULTS—A human chorionic gonadotropin (hCG) stimulation test was performed in 66 of 185 children with male undermasculinisation. In 41 of 66 patients the dose of hCG was either 1000 U or 1500U on three consecutive days. The rise in testosterone was related to basal serum testosterone and was not significantly different between the two groups. Testosterone:DHT ratio in patients with 5α-reductase deficiency was 12.5-72.8. During early infancy, baseline concentrations of LH and FSH were often within normal reference ranges. In patients with abnormal testes, median pre-LHRH (luteinising hormone releasing hormone) concentrations of LH and FSH were 2and 6.4 U/l, respectively, and post-LHRH concentrations were 21and 28 U/l. An exaggerated response to LHRH stimulation was observed during mid-childhood in children where the diagnosis was not clear and in all children with abnormal testes.
CONCLUSIONS—The testosterone:DHT ratio following hCG stimulation is more reliable than the basal testosterone:DHT ratio in identifying 5α-reductase deficiency. During infancy, the LHRH stimulation test may be more reliable in identifying cases of male undermasculinisation due to abnormal testes than basal gonadotrophin concentrations.
     

The GH-IGF-I axis and diabetes complications

Over 60 yr ago, Houssay demonstrated that removal of the pituitary improved the diabetes of animals and made them particularly sensitive to insulin ( Carbohydrate metabolism . BA Houssay. N Engl J Med 1936; 214: 971–975), and Young reported that permanent diabetes could be produced by injection of pituitary extract ( Permanent diabetes produced by pituitary ( anterior lobe ) injections. FG Young. Lancet 1937; ii: 372–374). Rolf Luft and colleagues in Sweden translated the Houssay model to humans by performing hypophysectomy in the hope of ameliorating vascular complications ( Hypophysectomy in man. R Luft, H Olivecrona, B Sjogren. Nord Med 1952; 47: 351–354). At the same time, remission of diabetic retinopathy was reported in a woman with long-standing type 1 diabetes when she developed postpartum anterior pituitary insufficiency (Sheehan's syndrome) ( The Houssay phenomenon in man: recovery from retinopathy in a case of diabetes with Simmonds' disease . JE Poulsen. Diabetes 1953; 2 : 7–12). In the 1960s and 1970s, there was considerable enthusiasm for pituitary ablation in the treatment of proliferative retinopathy, an approach happily supplanted by retinal photocoagulation.     

Pituitary-gonadal axis in male undermasculinisation.

AIMS: To study the value of assessing serum concentrations of luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in patients with male undermasculinisation not caused by androgen insensitivity. METHODS: A retrospective study of a register of cases of male undermasculinisation (20 with abnormal testes, eight with 5alpha-reductase deficiency, three with testosterone biosynthetic defects, seven with Drash syndrome, and 210 undiagnosed). RESULTS: A human chorionic gonadotropin (hCG) stimulation test was performed in 66 of 185 children with male undermasculinisation. In 41 of 66 patients the dose of hCG was either 1000 U or 1500 U on three consecutive days. The rise in testosterone was related to basal serum testosterone and was not significantly different between the two groups. Testosterone:DHT ratio in patients with 5alpha-reductase deficiency was 12.5-72.8. During early infancy, baseline concentrations of LH and FSH were often within normal reference ranges. In patients with abnormal testes, median pre-LHRH (luteinising hormone releasing hormone) concentrations of LH and FSH were 2 and 6.4 U/l, respectively, and post-LHRH concentrations were 21 and 28 U/l. An exaggerated response to LHRH stimulation was observed during mid-childhood in children where the diagnosis was not clear and in all children with abnormal testes. CONCLUSIONS: The testosterone:DHT ratio following hCG stimulation is more reliable than the basal testosterone:DHT ratio in identifying 5alpha-reductase deficiency. During infancy, the LHRH stimulation test may be more reliable in identifying cases of male undermasculinisation due to abnormal testes than basal gonadotrophin concentrations.     

Functional enteroinsular axis in full-term newborn infants

The term "enteroinsular axis" refers to the enhancement of insulin release by hormones secreted from the gut. Gastric inhibitory polypeptide (GIP) is one of the major hormones that mediates this function. The purpose of the present study was to examine whether the enteroinsular axis is functional in newborn infants born at term gestation. Between d 2 and d 4 of life, glucose was infused for 2 h intravenously or orogastrically to 44 fullterm newborn infants, of whom 18 were appropriate for gestational age, nine large for gestational age, eight small for gestational age; nine infants were born to diabetic mothers. Glucose was infused at either 8 mg/kg/min intravenously or 16 mg/kg/min orogastrically to achieve similar plasma glucose concentrations. Plasma insulin and GIP concentrations were compared. Plasma GIP concentration increased significantly with enteral glucose administration in all infants but remained unchanged with parenteral glucose infusion. The responses of plasma insulin and the insulin/glucose ratio were significantly greater in infants receiving enterally than parenterally infused glucose. However, when glucose was infused orogastrically at a lower rate (8 mg/kg/min), plasma GIP concentrations rose, but no enhancement of insulin response was detected, suggesting the importance of the role of circulating glucose in the "enteroinsular axis". The infants of diabetic mothers and the large-for-gestational-age infants had more rapid insulin response to orogastrically administered glucose, but their GIP responses were similar to that of normal infants. These findings suggest that, at term gestation, the newborn infants have a "functional" enteroinsular axis in response to glucose, i.e. the rising plasma GIP contributed in part to the enhanced insulin response to enterally infused glucose.(ABSTRACT TRUNCATED AT 250 WORDS)