Androgens Augment the Mitogenic Effects of Oocyte-Secreted Factors and Growth Differentiation Factor 9 on Porcine Granulosa Cells1
Androgens Augment the Mitogenic Effects of Oocyte-Secreted Factors and Growth Differentiation Factor 9 on Porcine Granulosa Cells1
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雄激素增强卵母细胞分泌因子和生长分化因子 9 对猪颗粒细胞的有丝分裂作用1
DOI：
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发表时间：
2005
影响因子：
3.6
通讯作者：
David T. Armstrong
中科院分区：
文献类型：
--
作者：
Theresa E. Hickey;D. Marrocco;F. Amato;L. J. Ritter;Robert J. Norman;R. Gilchrist;David T. Armstrong
摘要 在这项研究中，我们检验了雄激素对颗粒细胞的生长促进作用需要来自卵母细胞的旁分泌信号这一假设。在存在或不存在来自同一卵泡的裸卵母细胞 (DO) 的情况下培养来自小窦 (1-3 mm) 青春期前猪卵泡的壁颗粒细胞 (MGC)，以确定对 FSH、胰岛素样生长因子 1 (IGF1) 和二氢睾酮 (DHT) 组合的促有丝分裂和/或类固醇生成反应是否受到卵母细胞分泌因子 (OSF) 的影响。为了进一步探索这些因子的身份，我们进行了相同的实验，用生长分化因子 9 (GDF9)（一种已知的 OSF）代替 DO。 OSF 和 GDF9 均能有效增强 IGF1 刺激的增殖，并抑制 FSH 刺激的孕酮分泌。单独使用时，DHT 对 DNA 合成几乎没有影响，但在 IGF1 存在的情况下显着增强 OSF 或 GDF9 的促有丝分裂作用。裸卵母细胞、GDF9 和 DHT 独立抑制 FSH 刺激的黄体酮分泌，雄激素与 DO 或 GDF9 一起引起最有效的类固醇生成抑制。着眼于促有丝分裂作用，我们证明天然雄激素受体 (AR) 激动剂睾酮和 DHT 均剂量依赖性地增强 DO 或 GDF9 的促有丝分裂活性。抗雄激素（羟基氟他胺）治疗用于阻断雄激素受体活性，阻止雄激素和 GDF9 之间的相互作用。总之，雄激素通过涉及 AR 的机制增强卵母细胞或 GDF9 的生长促进作用，从而在体外刺激猪 MGC 增殖。这些信号通路可能是体内卵泡发生的重要调节因子，并且可能导致在雄激素处理的雌性动物中观察到的卵泡过度生长。
Abstract In this study, we test the hypothesis that the growth-promoting action of androgens on granulosa cells requires paracrine signaling from the oocyte. Mural granulosa cells (MGCs) from small antral (1–3 mm) prepubertal pig follicles were cultured in the presence or absence of denuded oocytes (DO) from the same follicles to determine whether mitogenic and/or steroidogenic responses, to combinations of FSH, insulin-like growth factor 1 (IGF1), and dihydrotestosterone (DHT) were influenced by oocyte-secreted factors (OSFs). To further explore the identity of such factors we performed the same experiments, substituting growth differentiation factor 9 (GDF9), a known OSF, for the DO. OSFs and GDF9 both potently enhanced IGF1-stimulated proliferation, and inhibited FSH-stimulated progesterone secretion. Alone, DHT had little effect on DNA synthesis, but significantly enhanced the mitogenic effects of OSFs or GDF9 in the presence of IGF1. Denuded oocytes, GDF9, and DHT independently inhibited FSH-stimulated progesterone secretion, and androgen, together with DO or GDF9, caused the most potent steroidogenic inhibition. Focusing on mitogenic effects, we demonstrate that both natural androgen receptor (AR) agonists, testosterone and DHT, dose-dependently augmented the mitogenic activity of DO or GDF9. Antiandrogen (hydroxyflutamide) treatment, which is used to block androgen receptor activity, opposed the interaction between androgen and GDF9. In conclusion, androgens stimulate porcine MGC proliferation in vitro by potentiating the growth-promoting effects of oocytes or GDF9, via a mechanism that involves the AR. These signaling pathways are likely to be important regulators of folliculogenesis in vivo, and may contribute to the excess follicle growth that is observed in androgen-treated female animals.
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影响因子：
--
作者：
Julia A. Elvin;Amander T. Clark;Pei Wang;N. Wolfman;M. Matzuk
通讯作者：
Julia A. Elvin;Amander T. Clark;Pei Wang;N. Wolfman;M. Matzuk
影响因子：
4.8
作者：
Isaac Y. Kim;J. H. Kim;D. Zelner;H. Ahn;H. Ahn;J. Sensibar;Chung Lee
通讯作者：
Isaac Y. Kim;J. H. Kim;D. Zelner;H. Ahn;H. Ahn;J. Sensibar;Chung Lee
生长分化因子 9 抑制人颗粒细胞和卵泡膜细胞中 35-单磷酸腺苷刺激的类固醇生成。
DOI：
10.1210/jcem.87.6.8551
发表时间：
2002
期刊：
The Journal of clinical endocrinology and metabolism.
影响因子：
--
作者：
Yamamoto,Noriko;Christenson,LaneK;McAllister,JanM;Strauss3rd,JeromeF
通讯作者：
Strauss3rd,JeromeF
影响因子：
6.1
作者：
Vendola, K;Zhou, J;Bondy, CA
通讯作者：
Bondy, CA
大鼠动情周期中卵巢芳香酶细胞色素 P450 和 5α-还原酶活性与 mRNA 水平之间的负相关关系。
DOI：
10.1016/0960-0760(92)90255-h
发表时间：
1992
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Lephart,ED;Doody,KJ;McPhaul,MJ;Simpson,ER
通讯作者：
Simpson,ER