[Expressions of ATF3 and CTGF and their regulation by estradiol in the prepuce of hypospadias patients].
OBJECTIVE
Estrogen is closely associated with hypospadias. The present study was to explore the molecular mechanism of hypospadias caused by estradiol.


METHODS
Fibroblasts obtained from the prepuce of hypospadiac and normal children were cultured in vitro and treated with 17-beta ethinyl estradiol (17-EE) at the concentrations of 1 micromol/L to 0.1 nmol/L for 2 hours, or at 0.1 micromol/L for 0.5, 1, 2, 4, 8, 16 and 24 hours. MTT assay was used to evaluate the effect of 17-EE on the proliferation of the cells, and RT-PCR was employed to detect the expressions of the activating transcription factor-3 (ATF3) and connective tissue growth factor (CTGF) in the hypospadiac tissue. The results were compared with those obtained from the nonhypospadiac tissue.


RESULTS
The expressions of ATF3 and CTGF were significantly upregulated in the hypospadiac tissue as compared with the nonhypospadiac group. At the concentration of 1 micromol/L, 17-EE significantly inhibited the proliferation of the cells. ATF3 mRNA was elevated at 1-2 hours, while CTGF mRNA showed no significant changes in 24 hours.


CONCLUSIONS
ATF3 and CTGF are two candidate genes involved in the etiology of hypospadias. And estradiol may induce hypospadias by upregulating the expressions of ATF3 and CTGF.
Zhou
Juan
J
Department of Urology, The Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Wang
Hao
H
Peng
Yu-Bing
YB
Chen
Qi
Q
Da
Jun
J
Wang
Zhong
Z
Ma
Li-Min
LM
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D052816:Foreskin / Q000378:metabolism*; D006801:Humans; D007021:Hypospadias / Q000235:genetics / Q000378:metabolism*; D008297:Male
C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C526317:CCN2 protein, human; D004967:Estrogens; D055513:Connective Tissue Growth Factor; D004958:Estradiol