Xi Guo Ph.D. , Yiping Zhong M.Phil. , Yang Liu M.Phil. , Rihan Wu M.Phil. , Ling Huang Ph.D. , Chuan Huang M.Phil. , Minghui Chen Ph.D.
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引用次数: 0
Abstract
Objective
To investigate the direct effect of growth differentiation factor 9 (GDF9) on androgen production in human theca cells.
Design
Experimental study.
Setting
Tertiary hospital-based research laboratory.
Patient(s)
Women who underwent in vitro fertilization and intracytoplasmic sperm injections at our clinic were included in this study.
Intervention(s)
Primary cultured human theca cells from women undergoing in vitro fertilization and intracytoplasmic sperm injection treatment were treated with GDF9, an activin receptor-like kinase 5 (ALK5) inhibitor, and a SMAD4 agonist.
Main Outcome Measure(s)
The expression of androgen synthesis-related genes StAR, CYP17A1, and LHCGR, levels of androstenedione and testosterone, phosphorylation of SMAD2/3, and the interaction between bone morphogenic protein-activated type II receptor and ALK5 were evaluated using reverse transcription-quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assays, and coimmunoprecipitation assays, respectively.
Result(s)
Growth differentiation factor 9 decreased StAR, CYP17A1, and LHCGR expression levels in human theca cells, which was prevented by treatment with the ALK5 inhibitor, and suppressed production of androgen in human theca cells. Growth differentiation factor 9 increased SMAD2/3 phosphorylation, and the ALK5 inhibitor also suppressed this effect. Bone morphogenic protein-activated type II receptor and ALK5 bound to each other after GDF9 stimulation. The SMAD4 agonist kartogenin also decreased messenger RNA levels of StAR and CYP17A1 and protein levels of StAR in human theca cells.
Conclusion(s)
Growth differentiation factor 9 can activate the bone morphogenic protein-activated type II receptor-ALK5-SMAD2/3 signaling pathway, suppress CYP17A1 expression, and decrease androgen production in human theca cells.