Apolipoprotein E peptide stimulation of rat ovarian theca cell androgen synthesis is mediated by members of the low density lipoprotein receptor superfamily.
Apolipoprotein E peptide stimulation of rat ovarian theca cell androgen synthesis is mediated by members of the low density lipoprotein receptor superfamily.
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载脂蛋白 E 肽对大鼠卵巢卵泡膜细胞雄激素合成的刺激是由低密度脂蛋白受体超家族成员介导的。
DOI：
10.1095/biolreprod61.3.665
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发表时间：
1999
影响因子：
3.6
通讯作者：
Dyer,CA
中科院分区：
文献类型：
--
作者：
Zerbinatti,CV;Dyer,CA
卵巢雄激素的产生是卵泡成熟的速度限制，可导致卵泡闭锁。因此，重要的是要确定卵巢内的药物，如载脂蛋白（apo）E，调节卵泡膜细胞雄激素的产生的行动。卵泡膜细胞雄激素的产生在低浓度时被刺激，在高浓度时被抑制。载脂蛋白E肽，乙酰基-Y（LRKLRKRLLRDADDL）2C或乙酰基-Y（141-155）2C，具有低密度脂蛋白（LDL）受体和LDL受体相关蛋白结合活性，并模拟天然载脂蛋白E在卵泡膜-间质细胞系统中的活性。为了定义LDL受体超家族成员在载脂蛋白E肽介导的反应中的作用，我们发现受体相关蛋白可以阻止刺激，而不会改变对雄烯二酮产生的抑制。载脂蛋白E肽（129-162），没有LDL受体结合活性，不刺激雄烯二酮的产生。当用肝素酶降解细胞表面硫酸乙酰肝素蛋白聚糖时，载脂蛋白E肽乙酰基-Y（141-155）2C不刺激雄烯二酮的产生。载脂蛋白E肽乙酰基-Y（141-155）2C与肝素结合，这是LDL受体配体的一种特性，在这种复合物中，肽对雄烯二酮的产生没有影响。这些观察结果支持的结论，载脂蛋白E介导的刺激，而不是抑制，卵巢卵泡膜细胞雄烯二酮的生产介导的LDL受体超家族的成员。
Ovarian androgen production is rate limiting for follicular maturation and can induce follicular atresia. Thus, it is important to define the actions of the intraovarian agents, such as apolipoprotein (apo) E, that modulate theca cell androgen production. Theca cell androgen production is stimulated at low concentrations and inhibited at higher concentrations of native apo E. The apo E peptide, acetyl-Y(LRKLRKRLLRDADDL)2C or acetyl-Y(141–155)2C, has low density lipoprotein (LDL) receptor and LDL receptor-related protein-binding activity, and it mimics the activity of native apo E in the theca-interstitial cell system. To define the role of members of the LDL receptor superfamily in the apo E peptide-mediated responses, we found that receptor-associated protein prevented the stimulation without altering the inhibition of androstenedione production. The apo E peptide (129–162), which has no LDL receptor-binding activity, did not stimulate androstenedione production. The apo E peptide acetyl-Y(141–155)2C did not stimulate androstenedione production when cell surface heparan sulfate proteoglycans were degraded with heparinase. The apo E peptide acetyl-Y(141–155)2C bound to heparin, a property of LDL receptor ligands, and in this complex the peptide had no effect on androstenedione production. These observations support the conclusion that apo E-mediated stimulation, but not inhibition, of ovarian theca cell androstenedione production was mediated by members of the LDL receptor superfamily.