瘦素与肥胖女孩特发性中枢性性早熟的关系

目的探讨瘦素对青春期启动的影响,瘦素与性腺轴激素之间的关系及其在肥胖女孩特发性中枢性性早熟(ICPP)发生中的作用。方法56例符合现行诊断标准的ICPP女孩,按是否肥胖分为2组:肥胖的ICPP组18例,非肥胖ICPP组38例,年龄匹配的青春期前儿童分为非肥胖未发育组25名,肥胖未发育组18名。测定其空腹血清瘦素、FSH、LH和雌二醇(E2)水平。结果与非肥胖未发育组血清瘦素浓度[(4.1±1.5)μg/L]比较,肥胖的ICPP组[(14.7±7.5)μg/L]、非肥胖的ICPP组[(8.8±5.1)μg/L]和肥胖未发育组[(8.0±5.3)μg/L]均明显升高(P<0.01或P<0.05);肥胖的ICPP组还明显高于肥胖未发育组及非肥胖的ICPP组(均P<0.05),但是肥胖未发育组及非肥胖的ICPP组之间差异无统计学意义。结论瘦素参与青春期发育的启动,肥胖女孩存在瘦素抵抗,肥胖女孩的高瘦素血症并非是引起其青春期发动提前的主要诱发因素。     

女孩特发性性早熟血清瘦素测定及意义

目的 观察瘦素在女孩性发育过程中的变化及临床意义。方法 利用放射免疫分析法（RIA）测定20例特发性性早熟（ICPP）女孩（其中A1组10例为6－7^11/12岁，A2组10例为8－9^11/12岁）血清瘦素水平，并与正常同年龄对照组女孩比较。结果 （1）ICPP（A1、A2）组女孩血清瘦素水平较正常同年龄对照组女孩明显升高，且差异有显著性；（2）A1、A2二组之间瘦素水平则差异无显著性；（3）血清瘦素水平与其体重呈正相关。结论 性发育启动需要一定的体重及瘦素水平，瘦素很可能是性发育启动的一个允许因子，对性发育过程起了促进作用。     

老年2型糖尿病患者血清瘦素浓度与甘油三酯水平的关系

目的　探讨老年糖尿病人血清瘦素浓度与甘油三酯水平的关系。方法　测定 10 0例老年糖尿病患者血清瘦素浓度与甘油三酯的水平 ,分析二者之间的关系。结果　老年糖尿病患者随甘油三酯水平升高血清瘦素浓度升高 (P <0 0 5 ) ,在相同甘油三酯水平 ,女性患者血清瘦素浓度高于男性患者 (P <0 0 5 )。结论　老年糖尿病患者血清瘦素浓度与甘油三酯水平有关。     

下丘脑能量信号通路通过调节Kiss1神经元对青春期发育的影响研究进展

青春期的启动主要受下丘脑能量信号通路的调控。下丘脑能量信号通路瘦素、腺苷酸活化蛋白激酶（AMPK）、G蛋白偶联受体54(GPR54)具有启动青春期发育和调控机体能量平衡的功能。Kiss1是刺激性成熟的主要内分泌因子,是调控下丘脑促性腺激素释放激素（GnRH）神经元的重要作用元件和下丘脑—垂体—性腺（HPG）轴成熟的调节因子,Kiss1作为GPR54的天然配体,与GPR54结合后调节GnRH分泌,对青春期发育起关键作用;瘦素是一种能量代谢的负反馈调节激素,下丘脑Kiss1神经元表达瘦素受体,介导瘦素对生殖系统产生影响;AMPK是重要的下丘脑能量感受器,在能量缺乏的条件下,AMPK被激活,抑制Kiss1 mRNA表达,在调节能量平衡及生殖方面起关键作用。机体能量代谢与青春期启动信号通路之间关系密切,研究青春期启动过程中调节能量平衡的信号通路,可以为治疗青春期发育异常和能量代谢失衡提供新治疗靶点。     

上海地区儿童和青少年血清瘦素水平与肥胖度,青春期？…

目的 研究上海地区儿童和青少年血清瘦素（ｌｅｐｔｉｎ）水平与肥胖度、青春期发育的关系。方法 用放射免疫分析法测定１０４例健康非肥胖男孩和１１８例健康非肥胖女孩（年龄在４．８岁至２０岁之间）的血清瘦素水平。结果 （１）无论是男孩还是女孩,血清瘦素水平均与体重指数（ＢＭＩ）呈正相关。在女孩,血清瘦素水平与年龄呈正相关;而在男孩,血清瘦素水平与年龄呈负相关。（２）随着年龄的增长,青春期发育的开始,女孩的     

血清瘦素浓度与甘油三酯水平的相关性

测定138例心血管病患者。结果:男性和女性中不同甘油三酯(TG)水平组的瘦素水平都不相同(F=38.426及30.457,P均<0.001;),随着TG水平的升高,血清瘦素的水平在男女性都有升高的趋势(F=67.077及49.786,P均<0.001),且女性瘦     

代谢性酸中毒对慢性肾衰患者血清瘦素水平的影响

目的初步探讨慢性肾功能衰竭(CRF)患者血清瘦素浓度的变化与代谢性酸中毒之间的关系.方法采用放射免疫分析法测定血清瘦素水平,观察代谢性酸中毒纠正前后CRF患者血清瘦素浓度的变化.结果正常人血清瘦素浓度为10.0±7.μg/L.CRF代谢性酸中毒患者血清瘦素浓度于纠酸前、纠酸后即刻和纠酸后3天分别为14.5±9.27、15.3±11.9、19.3±14.6μg/L,纠酸前、纠酸后即刻血清瘦素水平与正常对照组无明显差别,纠酸后3天血清瘦素浓度较纠酸前及正常对照组明显升高(P＜0.01).两组血清瘦素浓度与体重指数(BMI)均呈明显正相关,且女性血清瘦素浓度均分别高于男性(P＜0.01).结论①本研究提示,代谢性酸中毒可能对体内瘦素分泌具有抑制作用,且CRF患者的高瘦素血症很可能在某种程度上被酸中毒所掩盖.②CRF代谢性酸中毒患者中,女性血清瘦素水平明显高于男性.     

胰岛素样生长因子Ⅰ对儿童青春发育启动的作用

目的探讨胰岛素样生长因子Ⅰ(IGFⅠ)对正常儿童青春发育启动的可能作用。方法对北方大庆地区526名(男266,女260)健康的6～16岁小学和中学生进行4年的连续观察和研究。每年由相同的内分泌科医师进行体检,检查第二性征的发育,并按Tanner分期法行青春发育分期。同时采血用放射免疫测定或酶联免疫分析法测定血清LH、IGFⅠ和IGF结合蛋白3(IGFBP3)的水平。按年龄和青春发育分期分析血清LH和IGFⅠ、IGFBP3在青春发育过程中的变化及其关系。结果在儿童期不论是男孩还是女孩,随着年龄的增长,血清LH和IGFⅠ、IGFBP3水平有相似的升高趋势。男孩和女孩血清LH水平与IGFⅠ和IGFBP3水平都明显相关(均P<0.01)。血清IGFⅠ水平的开始明显升高在8岁,而LH水平的明显升高在10岁,表明血清IGFⅠ水平的升高要比LH升高早2年。以青春发育期进行分析,女孩在青春发育2期血清IGFⅠ水平明显高于1期,也早于LH水平升高(3期)。男孩则显示血清LH、IGFⅠ和IGFBP3水平在2期同时升高。结论儿童期循环中血清IGFⅠ水平的升高早于LH水平的升高,提示IGFⅠ可能是调节儿童青春发育启动的外周因素之一。     

非酒精性脂肪肝患者血清瘦素水平检测的临床意义

研究非酒精性脂肪肝患者血清瘦素水平检测的临床意义。选择门诊或住院患者非酒精性脂肪肝30例,正常对照30例,采用放射免疫法检测血清瘦素及胰岛素水平。结果发现,脂肪肝患者血清瘦素(23.7±13.1)μg/ml,胰岛素水平、(16.7±4.9)μg/ml显著高于正常对照组(4.7±3.2)μg/ml及(9.7±2.6)μg/ml,P<0.001。无论脂肪肝组还是正常对照组,血清瘦素水平升高存在性别差异,女性明显高于男性。脂肪肝患者存在瘦素抵抗和胰岛素抵抗,早期检测血清瘦素水平,为早期干预治疗脂肪肝提供了可能的途径。     

代谢综合征患者血清抵抗素、瘦素、C反应蛋白与体重和胰岛素抵抗的相关性

目的探讨代谢综合征（MS）患者血清抵抗素、瘦素和C反应蛋白（C-RP）水平与血脂、中心性肥胖和胰岛素抵抗（IR）的关系。方法50例MS男性患者和20例年龄相匹配的正常男性对照者（NC）,按腰围将MS患者分为肥胖组和非肥胖组,测定受试者空腹血清抵抗素、瘦素、C-RP、身高、体重、腰围、臀围、血压、血糖、血脂及胰岛素,计算HOMA-IR。结果MS患者肥胖组、非肥胖组和NC组相比血清抵抗素、瘦素、C-RP水平明显升高。结论MS患者血清抵抗素、瘦素及C-RP水平均明显升高,且与肥胖及IR程度明显相关,因而抵抗素、C-RP、瘦素可能在MS的发生发展中有重要作用。     

Physical changes of puberty

Normal pubertal development is characterized by major physical alterations: sexual maturation, changes in body composition, and rapid skeletal growth. Breast development is the first manifestation of puberty in approximately 85% of girls; the normal age for initial breast development is 8 to 13 years. Menarche generally occurs within 2 years of the onset of breast development, with a mean age in American girls of 12.8 years. In boys, the first manifestation of puberty is testicular enlargement; the normal age for initial signs of puberty is 9 to 14 years in males. Pubic hair in boys generally appears 18 to 24 months after the onset of testicular growth and is often conceived as the initial marker of sexual maturation by male adolescents. Skeletal growth is one of the most striking characteristics of puberty. Linear-growth velocity begins to increase in males at genital stage III and pubic-hair stage II, but peak height velocity is not attained until age 14 years in boys and 12 years in girls. Lean body mass, which primarily reflects muscle mass, begins to increase during early puberty in both boys and girls. Fat mass increases during the late stages of puberty in girls. Sex differences in the adolescent growth spurt produce the characteristics sexual dimorphism in shape and proportions seen in young adults.     

Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche.

Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.     

Relationship of plasma growth hormone-releasing hormone levels to pubertal changes

Basal plasma GH-releasing hormone (GHRH) concentrations were measured by RIA in 180 normal subjects (93 boys and 87 girls between the ages of 8 and 18 yr). Every subject was in good health and between -2 and +2 SD for height. Fourteen boys with delayed puberty also were studied. Plasma GHRH concentrations were higher during puberty than before it. At midpuberty, the mean GHRH levels in girls was 159.1 +/- 28.5 (+/- SEM) pg/ml, approximately 5-fold higher than the level in prepubertal girls (30.3 +/- 4.3 pg/ml). The mean plasma GHRH in midpubertal boys (101.4 +/- 11.5 pg/ml) was approximately 2-fold higher than the level in prepubertal boys (48.1 +/- 5.2 pg/ml). The GHRH levels in boys with delayed puberty more closely resembled those in boys at a similar pubertal stage than those in boys of similar chronological age. The dramatic rise in plasma GHRH levels during puberty suggests a role for this peptide in the adolescent growth spurt. Moreover, these data indicate that GHRH levels during adolescence may be a marker of the patient's pubertal development.     

Serum inhibin concentrations rise throughout normal male and female puberty

Using a newly developed, sensitive, and specific RIA, we measured the serum concentrations of inhibin, together with those of FSH, LH, and sex steroids, throughout puberty in 99 boys and 102 girls attending a suburban Melbourne school. Serum inhibin levels rose from a geometric mean level of 161 U/L (range, 87-310; 67% confidence interval) at stage I puberty in boys to 442 U/L (range, 300-626) at stage V, while corresponding values in girls were 97 U/L (range, 46-204) and 231 U/L (range, 187-372), respectively. Serum inhibin concentrations were strongly correlated with age and serum FSH, LH, testosterone, and estradiol; all hormones increased in parallel in both boys and girls. After adjustment for age, the partial correlation coefficients remained significant only for testosterone in the boys. We hypothesize that gonadal inhibin production is stimulated by rising gonadotropin levels during pubertal development.     

Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children

Several methods have been developed to assess insulin resistance (IR), insulin secretion, and sensitivity: some of them, such as the homeostasis model assessment (HOMA) for IR (HOMA IR) and for insulin secretion (HOMA beta cell) and the quantitative insulin sensitivity check index (QUICKI) are based on fasting levels of glucose (fasting G) and insulin (fasting I); others, such as the pancreatic insulin response to glucose (IRG) and the insulin sensitivity index (ISI) are derived from the glycemic and insulinemic responses to the oral glucose tolerance test (OGTT). The aim of the study was to compare these indexes in a large group of prepubertal and pubertal obese subjects and verify whether the data from fasting samples were enough for evaluating IR and insulin secretion or if OGTT was mandatory. A total of 405 obese subjects (221 boys and 184 girls) was studied. Ninty-three were prepubertal (Tanner stage I), 98 early pubertal (stage II to III) and 214 late pubertal (stage IV to V). In each subject, a 120-minute OGTT was performed, and the glycemic (mean blood glucose [MBG]) and insulinemic (mean serum insulin [MSI]) responses, expressed as AUC/120, as well as IRG and ISI were calculated. The fasting I/fasting G ratio (FIGR), HOMA IR, HOMA beta cell, and QUICKI were then measured. FIGR and HOMA IR increased in both sexes during puberty, but in girls, the increase was already evident from stage I to stage II to III, while in boys, it was evident only from stage II to III to stage IV to V. QUICKI decreased in girls at the onset of puberty and was lower than in boys in stage II to III; on the other hand, HOMA beta cell did not show any variation. IRG increased throughout puberty, although it was higher in boys than in girls in stages II to III and IV to V, while ISI decreased at the onset of puberty in boys; HOMA IR correlated with MSI and IRG, and HOMA beta cell with MSI in pubertal subjects only. In conclusion, the indexes deriving from fasting samples, such as FIGR and HOMA IR, proved to be enough for evaluating IR in prepubertal and pubertal obese subjects, as did QUICKI for insulin sensitivity, However, OGTT is still useful for assessing insulin secretion, because IRG is more sensitive in depicting the pubertal variations of IR than HOMA beta cell.     

Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children

OBJECTIVE: To define age at entry into Tanner stages in children with perinatal HIV-1 infection. DESIGN: Multicentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty. METHODS: The cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan-Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearman's rank correlation coefficient. RESULTS: Ages of girls [years (95%CI)] at P2 [12.9 (12.6-13.2)], P3 [13.4 (13.0-13.8)], P4 [14.6 (14.0-15.2)], B2 [12.7 (12.2-13.2)], B3 [13.3 (12.8-14.0)] and B4 [14.6 (14.0-15.2)] stages were > 97th percentile (> or = 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1-13.1)], P3 [13.9 (13.4-14.4)], P4 [14.9 (14.2-15.6)], G2 [12.1 (11.5-12.7)], G3 [13.6 (13.1-14.1)] and G4 [14.9 (14.1-15.7)] stages were at the 75-97th percentiles (< or = 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression. CONCLUSION: Perinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growth failure can exacerbate adolescents' feelings of being different and unwell.     

A longitudinal study of total and free thyroid hormones and thyroxine binding globulin during normal puberty

Thyroid hormones are essential for normal pubertal growth, yet the changes in total and, especially, free thyroid hormones and thyroxine-binding globulin during puberty have not been adequately defined. Serum from 39 normal children (20 girls, 19 boys) between the ages of 10 and 15 years were assayed for total T4, free T4, free T3 and thyroxine-binding globulin at 6-monthly intervals; the free hormone assays were valid, non-analogue methodologies. In the girls, free T4 levels fell from 15.7 +/- 0.6 pmol/l at 10 years to 13.0 +/- 0.6 (p less than 0.001) at 12.5 years before rising to 15.9 +/- 0.7 at 15 years; this nadir occurred at puberty stages 3-4. Changes in total T4 followed a similar pattern with a slight delay in the nadir (13 years, puberty stage 4). In the boys, free T4 fell from 16.3 +/- 0.6 pmol/l at 10 years to 14.3 +/- 0.3 at 13.5 years, then rising to 15.4 +/- 0.5 at 15 years; the nadir again occurred at puberty stages 3-4. The corresponding nadir in total T4 which occurred at puberty stages 4-5 was not apparent by age analysis. Thyroxine-binding globulin concentrations remained unchanged in the girls, but fell slightly in the boys during later puberty. Free T3 concentrations in the girls showed a progressive fall after 12.5 years which was significant by the age of 14 when most had been in puberty stage 5 for more than 1 year. The boys showed no change of free T3 concentration throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen receptor alpha regulates area-adjusted bone mineral content in late pubertal girls

CONTEXT: Whether the action of estrogen in skeletal development depends on estrogen receptor alpha as encoded by the ESR1 gene is unknown. OBJECTIVES: The aim of this study was to establish whether the gain in area-adjusted bone mineral content (ABMC) in girls occurs in late puberty and to examine whether the magnitude of this gain is related to ESR1 polymorphisms. DESIGN: We conducted a cross-sectional analysis. SETTING: The study involved the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based prospective study. PARTICIPANTS: Participants included 3097 11-yr-olds with DNA samples, dual x-ray absorptiometry measurements, and pubertal stage information. OUTCOMES: Outcome measures included separate prespecified analyses in boys and girls of the relationship between ABMC derived from total body dual x-ray absorptiometry scans and Tanner stage and of the interaction between ABMC, Tanner stage, and ESR1 polymorphisms. RESULTS: Total body less head and spinal ABMC were higher in girls in Tanner stages 4 and 5, compared with those in Tanner stages 1, 2, and 3. In contrast, height increased throughout puberty. No differences were observed in ABMC according to Tanner stage in boys. For rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms, differences in spinal ABMC in late puberty were 2-fold greater in girls who were homozygous for the C and G alleles, respectively (P = 0.001). For rs7757956, the difference in total body less head ABMC in late puberty was 50% less in individuals homozygous or heterozygous for the A allele (P = 0.006). CONCLUSIONS: Gains in ABMC in late pubertal girls are strongly associated with ESR1 polymorphisms, suggesting that estrogen contributes to this process via an estrogen receptor alpha-dependent pathway.     

Puberty in growth hormone-treated children born small for gestational age (SGA)

Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups.     

Leptin levels show diurnal variation throughout puberty in healthy children, and follow a gender-specific pattern.

OBJECTIVE: To investigate the levels and diurnal rhythm of serum leptin in healthy children, and to investigate the association between leptin levels and sex steroids. METHODS: Four girls and four boys, all healthy volunteers, were followed longitudinally throughout puberty. Their chronological ages ranged from 8.7 to 19.5 years, and body composition, expressed as weight-for-height standard deviation scores (SDS), ranged between -1.7 and +2.4. Serum leptin, oestradiol and testosterone concentrations were measured by radioimmunoassay at 1000, 1400, 1800, 2200, 0200 and 0600 h. RESULTS: In all girls and boys, both prepubertally and during pubertal development, serum leptin levels increased during the night, with no difference in relative peak amplitude. In boys, the leptin concentrations increased until the initiation of puberty and then declined, whereas in girls, the concentrations increased throughout puberty. The inter-individual variation in mean leptin levels among girls decreased to 11% at the time of menarche. A positive correlation was found for both oestradiol and testosterone versus leptin in girls throughout puberty (r=0.64 and r=0.71 respectively, P<0.001). A negative correlation was found between leptin and testosterone in boys in mid- and late puberty (r=-0.66, P<0.01). No correlation was found between oestradiol and leptin in boys or between testosterone and leptin in pre- and early pubertal boys. CONCLUSION: Serum leptin concentrations show diurnal variation throughout pubertal development in both girls and boys. The changes in leptin levels during puberty follow a gender-specific pattern, probably due to an influence of sex steroids on leptin production.