It is well known that a decline secular trend evaluated in the age of puberty onset.Sexual characteristics and linear growth spurt are two major events for puberty.The growth pattern of puberty characterized as acceleration-deceleration-cessation in growth velocity is specific for human being.It is modulated symphonically by both gonadal and somatotropic axes.This article reviews the advances in the modulming mechanisms of pubertal growth,particularly in the local sites of growth plate,and the concept of keeping positive balance between skeletal lineal growth and maturation.Finally,various therapeutic strategies for improving the final adult height in individuals with growth disorders during adolescence are discussed.

Objective To recognize the changes in the somatotropin axis function in girls with idiopathic central precocious puberty (ICPP) treated with GnRH analogue (GnRHa) and to probe into the cause of growth velocity reduction during GnRHa treatment. Methods Fourteen girls with ICPP were studied. Their growth velocities at the beginning and the end of 6th month of GnRHa treatment were observed. Maturation indexes (MI) were got from vaginal smears, and serum E 2, insulin like growth factor (IGF Ⅰ), IGF binding protein 3 (IGFBP 3) concentrations were determined and IGF Ⅰ/IGFBP 3 calculated at the beginning and the end of 6th month of GnRHa treatment. The controls were 13 age matched healthy prepubertal girls. Results After 6 month GnRHa treatment, the growth velocity reduced significantly from (8.23?1.67)cm/y to (6.27?1.54)cm/y (P

Objective To investigate the long-term outcome in the girls with central precocious puberty (CPP) treated by gonadotropin-releasing hormone analogue (GnRHa). Methods Thirty girls with idiopathic CPP treated with GnRHa for (23.0?7.6)months achieved their near final heights after (3.2?0.8)years follow-up. Comparisons were made among their final adult height (FAH), target height (THt), predicted adult height(PAH)at the onset and the end of GnRHa treatment (PAH 1 and PAH 2) . Factors affecting the height gain were also analysed. Results PAH increased after the GnRHa treatment [ PAH 2(155.2?5.7)cm vs PAH 1 (150.7?5.4)cm,P

Objective To explore the possible role of NROB1 gene played in regulating hypothalamic-pituitary-gonad axis(HPGA) by analyzing the clinical and molecular characteristics in a case of central precocious puberty(CPP) with NROB1 gene mutation. Methods Clinical characteristics and direct sequencing of NROB1 gene in the patient were analyzed. Results A 11-month-old boy with manifested premature puberty, enlargement of penis/testes, and penile erection, but without manifestations of adrenal insufficiency was reportd. Clinical diagnosis was adrenal hypoplasia congenita( AHC) with CPP. The NR0B1 gene sequencing revealed a novel mutation in exon 1 (913C> T). Conclusion NR0B1 gene mutation may lead to the development of CPP in the patient with AHC. However, the mechanism remains unclear and thus deserves further exploration.

0.05).(2) Expression levels of Akt : At baseline,Akt was already activated in NCU-SGA rats compared to no Akt activation in normal control rats.However,post-stimulating of insulin,the increase level of phosphate Akt in NCU-SGA rats was remarkably lower than that in control rats(P

Child ; China ; Endocrinology ; history ; History, 20th Century ; History, 21st Century ; Humans ; Pediatrics ; history

[Objective] To observe the effect of stanozolol on proliferation and differentiation of cultured growth plate chondrocytes in vitro.[Methods] At 3 week of age,Sprague–Dawley rats received 2.5 mg/kg in slow-released GnRHa (triptorelin) which was repeated every 2 weeks for 2 times,at 7-week old.The tibial growth plate cartilage were aseptically dissected and tripsin and EDTA digested for 0.5 h,then collagenase digested for 3 h at 37 ℃.Chondrocytes were cultured in DMEM:F12 medium for 48 h,the cells were starved for 24 h in serum-free DMEM:F12 medium before stanozolol treatment.In dose-effect groups,chondrocytes were incubated in serum-free media in various concentrations of stanozolol for 48 h.In time-course groups,chondrocytes were incubated in serum-free media in various times of stanozolol (10-8 mol/L).immunohistochemical staining of collagen Ⅱ,Ⅹ,PCNA,and MTT were conducted.[Results] The results of MTT,PCNA,and typeⅡcollagen synthesization demonstrated stanozolol enhanced the proliferation of the chondrocytes,time-course studies had shown that the proliferation were maximally stimulated by stanozolol after 2 or 3 days of incubation and decreased again after longer periods of incubation.Stanozolol stimulated the proliferation of the chondrocytes dose-dependently at 10-11 mol/L and 10-8 mol/L,maximally stimulatory concentrations of Stanozolol was 10-9 ～ 10-8 mol/L,and decreased again after higher concentration of stanozolol.Stanozolol did not stimulated type X collagen synthesization from 10-11 mol/L ～ 10-8 mol/L,but experiments showed that type X collagen was already stimulated after incubation in Stanozolol (10-7 ～ 10-5 mol/L).Time-course studies had shown those typeⅩcollagen synthesizations were stimulated by stanozolol after 4 ～ 5 days of incubation.[Conclusion] Stanozolol enhances the proliferation of chondrocytes of pubertal female rat treated with GnRHa in vitro (time-course- dependent and concentration -dependent).

Objective To investigate the possible mechanism of the effect of short-term gonadotropin-re-leasing hormone agonist(GnRHa)on linear growth in female pubertal rats. Methods Forty 3-week-old female rats were randomly divided into 5 groups(n=8 each). One group was sacrificed as base-line control. Group OVX was operated for ovariectomy at the beginning of experiment. Group Gn and group E2 each received two intramuscu-lar injections of 2.5mg·kg-1 triptorelin 2 weeks apart, and group E2 received additional daily 1μg·kg-1·d-1estradiol(E2)s. c. at three days after the second GnRHa injection for 11 days. Group Ctrl was sham-operated ascontrol. Each rat, except for the base-line control group. received 30mg/kg oxytetracycline s. c. and 20mg/kgcalcein s. c. 9 and 2 days respectively before sacrifice. Hepatic GH receptor mRNA, insulin-like growth factor(IGF)-I and IGF binding protein(IGFBP)-3, circulating IGF-I and IGFBP-3, local IGF-I/IGF-I receptor(IGF-IR)and proliferation rate(PFR)in epiphyseal growth plate(EGP)were evaluated after 4-week treatment.Results Similar to group OVX, the rats in group Gn became taller and heavier than group Ctrl with greater tibial length, wider EGP, greater longitudinal growth rate(LGR)and higher PFR(P<0.05 or P<0.01). Estrogen supplement reversed the effect of GnRHa. There was no statistical difference among the 4 groups regarding plasma IGF-I and IGFBP-3, hepatic IGF-I and IGFBP-3 mRNA levels, local IGF-I and IGF-I R levels in EGF. GnRHa down-regulated hepatic GHR mRNA expression, which was reversed by estrogen supplement. Conclusion GnRHa accelerates longitudinal growth of female pubertal rats. Estrogen deprivation contributes to GnRHa-induced alteration of linear growth in female rats, through improving PFR and suppressing the senescence of EGP. The underlying mechanism does not attribute to endocrine change of GH/IGF-I axis or local IGF-I/IGF-IR in EGP.

Objective To analyze the pattern of early catch-up growth In children with prepubertal short stature and various secretory forms of growth hormone(GH)following recombinant human growth hormone (rhGH)treatment and to explore the mechanism. Methods Sixty-two children with prepubertal short stature and various GH secretory forms were analyzed retrospectively, 27 with complete growth hormone deficiency (cGHD), 23 with partial growth hormone deficiency (pGHD)and 12 with idiopathic short stature(ISS). According to the GH peak value in GH provocative test, the group of pGHD was divided into pGHD-1(5.0-6.9μg/L)and pGHD-2(7.0-9.9μg/L). Height velocity, increase in height standard differentiation score (SDS), was calculated; serum levels of somatotrophic axis hormone were detected and bone age was determined. Results The quick early catch-up growth in different groups were similar in the initial 6 months. While that in the ISS group persisted for shorter period and was correlated with lower level in serum GH-binding protein(r=0.526,P=0.025)and Δinsulin-like growth factor-binding protein-3 (IGFBP-3) SDS (r=0.532,P=0.034) after rhGH treatment. The same doses of rhGH were applied to children with cGHD and pGHD. Children with pGHD-1 showed similar response to rhGH,regarding height velocity and ΔIGFBP-3 SDS, as compared with those of cGHD. However, children with pGHD-2 presented similar response with ISS, being worse than cGHD. Conclusion Downregulation of GH receptor and decrease in post-receptor effect seem to be the mechanism leading to early retardation in ISS. The incomplete catch-up growth in pGHD-2 may be caused by relatively inadequate rhGH dose. The cut-off value of GH provocative test in diagnosing GHD is more reasonable to be 7μg/L.

Objective To understand how serum DHEAS levels change with sex,age and stage of sexual maturation in children and adolescents and explore the relationship between adrenarche and pubertal maturatiotL Methods Serum samples from 120 healthy boys,198 healthy girls and 152 girls with idiopathic central precocious puberty (ICPP) were examined for DHEAS.Referenee ranges for healthy children and adolescents and statistical difierences between heahhy girls and ICPP girls were analyzed with respect to sex,age and stage of sexual maturation.Results Both healthy children and ICPP girls showed extremely low levels of serum DHEAS and they were not related to sex.age or tanner stages in the individuals below age of 6 years.Serum DHEAS levels were positively related to both age (above age of 6 years)and tanner stage in healthy groups(r=0.69 and 0.71 respectively,P＜0.01).After the onset of puberty,serum DHEAS levels appeared to be higher in boys than that in girls within the same tanner stage(P＜0.05).Within the individusis in the same age group with same sex.serum DHEAS levels increased along with pubertal development.While within the individuals in same tanner stage group with salne sex after puberty onset.serum DHEAS levels showed no significant difference among different age groups.For example.there was no difference in serum DHEAS levels of healthy girls in tanner stage Ⅲ among different age subgroups(age of8-9;age of 10-11,age of 12-13)and the mean vallie of serum DHEAS was 532.0-557.8μg/L(F=0.21,P=0.98).In different age subgroups above age of 6 years,Z scores for serum DHEAS in ICPP girls were highher than them healthy ones with advanced tanner stages(0.97us-0.1 and 1.39us-0.08,JP≤0.01)In different tanner stage subgroups.Z scores for serum DHEAS showed no difierence between healthy and ICPP girls despite apparent different age ranges(0.00 us-0.31-0.18,P＞0.05).Conclusions Serum DHEAS level increased along with both age (above 6 years) and tanner stage in healthy children and adolescents.There was no gender difference until the onset of puberty.It was demonstrated that adrenache and gonadarche were related to each other.Reference ranges for adolescents should be interpreted according to sex.age and tanner stage simultaneously.