Activin A Stimulates Aromatase via the ALK4-Smad Pathway in Endometriosis.
Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA. Cumulatively, these data suggest that Activin A promotes the secretion of estradiol from ESCs by increasing the expression of P450arom via the ALK4-Smad pathway. These findings indicate the ALK4-Smad pathway may promote ectopic lesion survival and development.
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China; Center of Reproductive Medicine, 174th Hospital of PLA, Xiamen 361000, China.
Juan
J
Zheng
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Juan
J
Qu
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Pinhong
P
Lu
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Zhen
0000-0001-7723-6749
Z
Hou
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Yugui
0000-0002-2866-6096
Y
Cui
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Yundong
Y
Mao
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Xiaochen
X
Qi
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Hui
H
Ji
State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Jiayin
J
Liu
D030201:Activin Receptors, Type I / Q000378:metabolism*; D028341:Activins; D000328:Adult; D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism*
C497796:SMAD4 protein, human; D051901:Smad4 Protein; C422405:activin A; D028341:Activins; D001141:Aromatase; C561410:CYP19A1 protein, human; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I