To investigate the effect of estrogen on cell proliferation and expression of proteins of C-type natriuretic peptide (CNP), natriuretic peptides B receptor (NPR-B) and natriuretic peptides C receptor (NPR-C) in ATDC5 cells during chondrogenesis.ATDC5 cells were induced for differentiation with insulin 10 µg/ml (day 0), and were started to be investigated on day 6. They were incubated with: (1) Estradiol (E2) at different concentrations (10(-11)-10(-5) mol/L) for 24 hours (for studying cell proliferation), or for 48 hours (for studying CNP, NPR-B and NPR-C protein expression); (2) E2 (10(-8) mol/L) for 24, 48, 72, 96 and 120 h (for studying cell proliferation), or for 24, 48, 72 and 96 hours (for studying CNP, NPR-B and NPR-C protein expression); (3) E2 (10(-8) mol/L) , and/or ICI 182782 (estrogen receptor antagonist ) (10(-7) mol/L) for 24 hours (for studying cell proliferation). ATDC5 cells proliferation were determined by MTT (OD value). Western-blotting was performed to identify the protein levels of CNP, NPR-B and NPR-C.(1) After incubation with E2 (10(-11)-10(-5) mol/L) for 24 h, ATD5 cell number increased with the increasing E2 concentration, peak in E2 concentrations of 10(-9) and 10(-8) mol/L (0.56 ± 0.06 and 0.52 ± 0.02, P < 0.05 and <0.01, respectively) , while significantly decreased in E2 (10(-5) mol/L) (0.30 ± 0.02) compared with DMSO-control (0.38 ± 0.02) (P < 0.05). After incubation with E2 (10(-11)-10(-5) mol/L) for 48 h, the protein level of CNP, NPR-B and NPR-C increased significantly, with the greatest effect seen at a concentration of 10(-10) mol/L E2 for CNP and NPR-B, 10(-9) mol/L E2 for NPR-C (P < 0.05). (2) After incubation with E2 (10(-8) mol/L) for 24 to 96 hours: (1) The cell number in each of the four time points was significantly increased compared with DMSO-control, with the greatest effect in 48 h (0.030 ± 0.003) (P < 0.05 or <0.01, respectively). While the cell number at 120 h was similar to that in DMSO-control. (2) The protein level of CNP increased significantly at 24 h (P < 0.05), seemed to be increased at 48 h and 72 h and decreased at 96 h. Both NPR-B and NPR-C level seemed to be increased at 24 h (P = 0.060 and 0.055, respectively) and seemed to decrease at 48 h, with decreasing significantly at both 72 h and 96 h (P < 0.05). (3) After incubation for 24 h, there was significant difference among the cell number of the four groups (P < 0.05). Cell number of group E2 (0.470 ± 0.032) was increased compared with group (E2+ICI) (0.410 ± 0.018), both being increased compared with group DMSO-control (0.370 ± 0.011, P < 0.05, respectively). There was no difference in cell number between group ICI 182782(0.360 ± 0.035) and group DMSO-control.E2 promotes the proliferation of ATDC5 cells i.e. chondrogenesis via estrogen receptor mediated mechanism, in both concentration-dependent and time-dependent manner. E2 (10(-11)-10(-8) mol/L) up-regulates protein expression of CNP, NPR-B and NPR-C of ATDC5 cells during chondrogenesis, and regulate the expression of the three proteins mentioned above positively or negatively at different time point, which implied that estrogen is one of the regulators of CNP signaling pathway.
Objective To evaluate the long-term final adult height outcome of combined treatment with gonadotropin-releasing hormone analogue(GnRHa)and recombinant human growth hormone(rhGH)in girls with idiopathic central precocious puberty(ICPP).Methods Out of 49 sirls with ICPP[treated with GnRHa at a dose of 60-80 μg/kg every 4 weeks for at least 6 months,whose height velocity fell below 4 cm/year and showed no improvement of predicted adult height(PAH)in 6 months],26 received(rhGH-combined group),in addition to chronological age,and duration of GnRHa treatment,who showed the same growth pattern but refused rhGH treatment,served to evaluate the efficacy of rhGH in addition.At the conclusion of the smdy,all the girls had been followed up for(3.3±1.9)years,and(3.2±0.9)years in rhGH-combined group and control group,respectively;and had achieved adult heisht.To compare the PAH with the final adult height(FAH)before and after treatment in the two groups.Results During rhGH treatment, height velocity of the rhGH-combined girls increased significantly[(6.7±2.0 vs <4)cm/year baseline],RhGH-combined gids showed an adult height far higher than pretreatment PAH [(157.5±4.5 vs 148.1±4.6)cm,P<0.01],and target height[(154.4±4.6)cm] was,significantly excceded.The control group reached an adult heisht also significandy higher than pretreatment PAH[(154.7±5.5vs 150.3±6.0)cm,P<0.01],while target height[(155.6±4.3)cm]was just reached but not significantlyexcceded.The gain in height obtained,calculated between pretreatment PAH and final heisat,(9.4±4.9)cm in rhGH-combined group was much more than that(4.3±4.2)cm in the control group(P<0.01).Conclusion RhGH may accelerate the linear growth and improve adult height of GnRHa-treated ICPP girls.
Key words:
Gonadotropin-releasing hormone analogue; Growth hornmne; puberty,precocious; Adult height
Background: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism caused by mutations in Glut2.To date there is no case has been reported from China.Objective and hypotheses: To summarize the clinical characteristics of FBS.Methods: We reported the first two cases of FBS in China.We summarized the clinical characteristics of FBS by reviewing the 2 cases and published literature. Results:The both cases presented similar manifestations as reported, including severe short stature, hypoglycemia, hepatomegaly secondary to glycogen accumulation, severe glycouremia secondary to proximal renal tubular dysfunction.And more points may help to differentiate FBS and type I glycogen storage disease(GSD I) including glucose intolerance with normal lactic acid and uric acid, possible and slightly glucose response to glucagon stimulation without accumulation of lactic acid, severe symptoms of hypophosphatemia and rickets, and metabolic acidosis caused by type II renal tubular acidosis.After receiving symptomatic treatment both children presented catch-up growth.Conclusions: FBS is a rare inherited disease caused by mutations in Glut2.It should be carefully differentiated from GSD I and diabetes mellitus in clinical practice.Symptomatic treatment can be helpful.
[Objective] To provide a descriptive analysis of Fanconi-Bickel syndrome(FBS),which is a rare inherited disease caused by mutations in the glucose transporter 2(GLUT2) gene and is not well characterized in China.[Methods] We reported the first two cases of FBS in China and described the clinical characteristics of FBS by combining our results with a review of the literatures.[Results] Both of the two affected children who were confirmed by genetic analysis of GLUT2 gene presented with manifestations similar to Glycogen Storage Disease Type 1(GSD-I),severe short stature,hypoglycemia,hepatomegaly secondary to glycogen accumulation.However,post prandial hyperglycemia,glycosuria and hypophosphatemic rickets secondary to proximal renal tubular dysfunction,type II renal acidosis without elevated lactic acid and uric acid in FBS do not developed in GSD-I.As the characteristics of being born as small for gestational age and apparent liver dysfunction in our children have been seldom described in the literatures,the present study will supplement the up-to-date clinical characteristic spectrum for FBS.[Conclusions] FBS should be differentiated from GSD-I and diabetes mellitus.Careful medical history collection,physical examination,laboratory data evaluation,imaging studies and liver biopsy are helpful in making the correct diagnosis.
C-type natriuretic peptide (CNP) is an important local regulator of long bone growth. It catalyzes the synthesis of cGMP after binding to its receptor natriuretic peptide receptor-B (NPR-B) ,and regulates long bone growth by activating downstream factors. Though the mechanism of the regulation of CNP signaling remains unclear, it has been demonstrated that CNP signaling has a cross-talk with the fibroblast growth factor receptor 3 pathway in cartilate.Heterozygous NPR-B mutations maybe one of the molecular basis of idiopathic short stature. CNP can be used as a biological marker of linear growth, with great importance in growth monitoring, diagnosis and treatment of growth disorders.The research on the mechanism of CNP signaling system in endochondral ossification will contribute to a new medication for bone development disorders in the future.
Key words:
Natriuretic peptide,C type; Long bone growth; Growth plate
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