Granulosa cell modulation of luteinizing hormone-dependent androgen production by ovarian theca-interstitial cells: a temporal switch from suppression to augmentation stimulated by follicle-stimulating hormone in vitro.
Granulosa cell modulation of luteinizing hormone-dependent androgen production by ovarian theca-interstitial cells: a temporal switch from suppression to augmentation stimulated by follicle-stimulating hormone in vitro.
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颗粒细胞对卵巢卵泡膜间质细胞黄体生成素依赖性雄激素产生的调节：体外促卵泡激素刺激的从抑制到增强的暂时转换。
DOI：
10.1095/biolreprod53.4.758
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发表时间：
1995
影响因子：
3.6
通讯作者：
Magoffin,DA
中科院分区：
文献类型：
--
作者：
Zachow,RJ;Magoffin,DA
优势卵泡颗粒细胞(GC)分泌雌二醇-17β(E_2)依赖于黄体生成素(LH)刺激的卵泡膜间质细胞(TIC)合成雄激素。最近的证据表明，卵泡内的旁分泌系统，由FSH调节，并涉及GC，可能通过TIC调节依赖于黄体生成素的雄激素的产生。在本研究中，我们研究了GC和FSH在调节黄体生成素依赖的TIC和雄酮产生中的作用。在完整未成熟大鼠分散的全卵巢细胞(包括GC和TIC)的培养中，黄体生成素刺激雄酮的产生增加10倍(最大雄酮=21.0±1.1 ng/ml)。与之相比，去垂体未成熟大鼠分散的全卵巢细胞经促黄体生成素刺激后，雄酮产量增加了50倍(108±18 ng/ml)。两种细胞制剂对黄体生成素的EC50(0.02±0.001 ng/ml)相同。我们推测，完整大鼠的全卵巢细胞培养产生较少的雄激素是由于GC的抑制。为探讨GC在调节TIC雄激素产生中的作用，将高纯度的未成熟大鼠TIC与未成熟大鼠的GC共同培养。GC数量的增加(每孔2.5x100x103GC)导致TIC产生的黄体生成素依赖性雄酮逐渐减少。此外，重组人卵泡刺激素(RFSH)刺激的GC(是促黄体生成素刺激的TIC对照的54%)的条件培养液抑制了依赖于黄体生成素的雄酮的产生，这表明GC分泌的一个或多个旁分泌因子参与了这一过程。在这个模型中，培养液中的E2浓度大约是先前显示的削弱TIC雄激素产生的30倍。培养至48h时，rFSH可增强GC对TIC雄酮产生的抑制作用，而rFSH在96h时可刺激LH型雄酮的产生，提示GC通过旁分泌机制抑制LH型TIC雄酮的产生。重要的是，最初的抑制作用被FSH增强；但随着FSH的继续治疗，检测到了刺激效应。因此，FSH可诱导GC由产生一种或多种抑制性旁分泌因子转变为产生可通过TIC调节黄体生成素依赖性雄激素产生的刺激性旁分泌因子。这可能是一种确保卵泡存活和促进优势卵泡选择的机制。
The production of estradiol-17β (E2) by granulosa cells (GC) of the dominant follicle is dependent upon LH-stimulated synthesis of androgens by ovarian theca-interstitial cells (TIC). Recent evidence has pointed toward an intrafollicular paracrine system, regulated by FSH and involving GC, that may modulate the LH-dependent production of androgens by TIC. In the present study, the role of GC and FSH in modulating LH-dependent TIC and androsterone production was examined. In cultures of dispersed whole ovarian cells (containing populations of both GC and TIC) from intact immature rats, LH stimulated a 10-fold increase in androsterone production (maximum androsterone = 21.0 ± 1.1 ng/ml). By comparison, androsterone production was increased 50-fold in LH-stimulated cultures of dispersed whole ovarian cells from hypophysectomized immature rats (108 ± 18 ng androsterone/ml). TheEC50for LH (0.02 ± 0.001 ng/ml) was identical in the two cell preparations. We hypothesized that the lesser androgen production by whole ovarian cell cultures from intact rats was due to suppression by the GC. To investigate the role of GC in modulating TIC androgen production, highly purified TIC from immature hypophysectomized rats were cultured in the presence of GC obtained from intact immature rats. Increasing numbers of GC (2.5−100 x 103GC per well) caused a progressive decrease in LH-dependent androsterone production by TIC. Additionally, LH-dependent androsterone production was suppressed by the conditioned medium from recombinant human FSH (rFSH)-stimulated GC (54% of the value for LH-stimulated TIC controls), indicating the involvement of a GC-secreted paracrine factor or factors. E2concentrations in the medium were approximately 30-fold below those previously shown to impair TIC androgen production in this model. Up to 48 h in culture, rFSH potentiated the suppressive effect of GC on TIC androsterone production in cocultures; however, rFSH stimulated LH-dependent androsterone production at 96 h. These results indicate that GC suppress LH-dependent TIC androsterone production by a paracrine mechanism. Importantly, the initial inhibitory effect was potentiated by FSH; but with continued FSH treatment, a stimulatory effect was detected. Hence, FSH may induce GC to change from production of one or more inhibitory paracrine factors to production of stimulatory paracrine factors that can modulate LH-dependent androgen production by TIC. This may be a mechanism to ensure the viability and promote selection of the dominant follicle.