Antimullerian hormone inhibits follicle-stimulating hormone-induced adenylyl cyclase activation, aromatase expression, and estradiol production in human granulosa-lutein cells

Antimullerian hormone inhibits follicle-stimulating hormone-induced adenylyl cyclase activation, aromatase expression, and estradiol production in human granulosa-lutein cells
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DOI:
10.1016/j.fertnstert.2013.04.019
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发表时间:
2013-08-01
影响因子:
6.7
通讯作者:
Leung, Peter C. K.
Leung, Peter C. K.
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Hsun-Ming;Klausen, Christian;Leung, Peter C. K.

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目的:探讨抗苗勒管激素(AMH)对基础和FSH诱导的细胞色素P450芳香化酶的影响(芳香化酶)的表达和E-2的产生,并阐明AMH发挥其作用的机制。设计:实验研究。设置:生殖科学学术医学中心。患者:hGL细胞来自同意接受IVF治疗的患者。干预措施:无。主要结果测量:原代培养的hGL细胞用于检查AMH的作用(10 ng/mL)基础和FSH(0.2 IU/mL)刺激的E-2和细胞内环腺苷30:50单磷酸(cAMP)蓄积,以及芳香酶和FSH受体表达。结果:AMH处理显著降低FSH刺激的芳香化酶表达和E-2积累,而对基础水平和/或8-Br-cAMP刺激的水平没有可测量的影响。FSH受体信使RNA和蛋白质水平在AMH处理的细胞中没有改变。AMH抑制FSH诱导的细胞内cAMP的增加。结论:AMH通过AMHR 2抑制FSH诱导的腺苷酸环化酶的激活、芳香化酶的表达和E-2的产生。(C)2013年,美国生殖医学会(American Society for Reproductive Medicine)
Objective: To investigate the effects of antimullerian hormone (AMH) on basal and FSH-induced cytochrome P450 aromatase (aromatase) expression and E-2 production in human granulosa-lutein (hGL) cells, and to elucidate the mechanism by which AMH exerts its effects.Design: Experimental study.Setting: Academic medical center for reproductive science.Patient(s): The hGL cells were obtained from consenting patients undergoing IVF treatment.Intervention(s): None.Main Outcome Measure(s): Primary cultures of hGL cells were used to examine the effects of AMH (10 ng/mL) on basal and FSH (0.2 IU/mL)-stimulated E-2 and intracellular cyclic adenosine 30: 50 monophosphate (cAMP) accumulation, as well as aromatase and FSH receptor expression. Small interfering RNA targeting type II AMH receptor (AMHR2) was used to verify the specificity of the effects.Result(s): Treatment with AMH significantly reduced FSH-stimulated aromatase expression and E-2 accumulation, whereas it had no measurable effects on basal and/or 8-Br-cAMP-stimulated levels. The FSH receptor messenger RNA and protein levels were not altered in AMH-treated cells. Cotreatment with AMH suppressed FSH-induced increases in intracellular cAMP. Knockdown of AMHR2 reversed the effects of AMH on aromatase expression.Conclusion(s): The AMH acts through AMHR2 to inhibit FSH-induced adenylyl cyclase activation, aromatase expression, and E-2 production. (C) 2013 by American Society for Reproductive Medicine.