Misajon A, Hutchinson P, Lolatgis N, Trounson A O, Almahbobi G
Centre for Early Human Development, Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
Mol Hum Reprod. 1999 Feb;5(2):96-103. doi: 10.1093/molehr/5.2.96.
We investigated aromatization and the mechanism of action of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) on oestradiol biosynthesis in freshly prepared granulosa cells from polycystic ovaries. Freshly prepared granulosa cells from polycystic ovaries incubated for only 3 h under basal conditions secreted significantly (P< 0.001) greater amounts of oestradiol-17beta than that of granulosa cells from normal ovaries. 8-Bromo-cyclic adenosine monophosphate (8-Br-cAMP), but not follicle stimulating hormone (FSH) or luteinizing hormone (LH), further enhanced this activity. Both EGF and TGFalpha inhibited gonadotrophinor 8-Br-cAMP-stimulated, but not basal, oestradiol production. LH receptor (LHR) binding, estimated by immunolabelling the bound LH, was significantly (P< 0.001) reduced in granulosa cells from polycystic ovaries when compared with cells from normal ovaries. EGF or TGFalpha significantly reduced the binding in cultured cells from all patient groups (P< 0.05). More interestingly, a further increase of the inhibitory effect was seen in granulosa cells from polycystic ovaries (P < 0.001). In conclusion, granulosa cells from polycystic ovaries contain high levels of basal aromatase activity in vitro, which is probably inherited from the in-vivo condition. EGF and TGFalpha suppress oestradiol synthesis at a step beyond the production of cAMP and also LHR binding with more effect in granulosa cells from polycystic ovaries.
我们研究了芳香化作用以及表皮生长因子（EGF）和转化生长因子α（TGFα）对多囊卵巢新鲜制备的颗粒细胞中雌二醇生物合成的作用机制。多囊卵巢新鲜制备的颗粒细胞在基础条件下仅孵育3小时，其分泌的17β-雌二醇量显著（P<0.001）高于正常卵巢的颗粒细胞。8-溴环磷酸腺苷（8-Br-cAMP）可进一步增强这种活性，而促卵泡激素（FSH）或促黄体生成素（LH）则不能。EGF和TGFα均抑制促性腺激素或8-Br-cAMP刺激的雌二醇生成，但不抑制基础雌二醇生成。通过对结合的LH进行免疫标记估计，多囊卵巢颗粒细胞中的LH受体（LHR）结合与正常卵巢细胞相比显著（P<0.001）降低。EGF或TGFα可显著降低所有患者组培养细胞中的结合（P<0.05）。更有趣的是，在多囊卵巢颗粒细胞中观察到抑制作用进一步增强（P<0.001）。总之，多囊卵巢颗粒细胞在体外含有高水平的基础芳香化酶活性，这可能是从体内状态遗传而来的。EGF和TGFα在cAMP产生之外的步骤抑制雌二醇合成，并且对多囊卵巢颗粒细胞中的LHR结合具有更大的影响。
