Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells
Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells
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DOI：
10.1095/biolreprod64.2.451
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发表时间：
2001-02-01
影响因子：
3.6
通讯作者：
Magoffin, DA
中科院分区：
文献类型：
--
作者：
Huang, CTF;Weitsman, SR;Magoffin, DA
启动卵巢卵泡膜细胞（TC）分化的信号是不依赖促性腺激素的，因为卵泡膜前体细胞不含LH受体。以前我们证明腔前卵泡产生旁分泌TC分化因子，通过LH非依赖性机制促进雄激素的产生。本研究测试了两种颗粒细胞产生的肽，胰岛素样生长因子-I（IGF-I）和干细胞因子（SCF）对TC分化和雄激素产生的影响。IGF-I或SCF的中和抗体可阻断卵泡条件培养基对TC前体分化的刺激作用超过90%。用梯度离心法从去垂体的未成年大鼠卵巢中分离TC，并与SCF（0-100 ng/ ml）和ICF-I（0 - 100 ng/ml）共同培养48 h，观察SCF和ICF-I对TC分化的影响。放免法测定培养液中雄酮含量。通过特异性逆转录聚合酶链反应测定黄体生成素受体、类固醇生成急性调节蛋白（星星）、CYP 11 A、CYP 17和3 β-羟基类固醇脱氢酶（3 β-HSD）mRNA。干细胞因子或IGF-I单独不刺激雄酮的产生，但在组合引起浓度依赖性增加雄酮水平。最大雄酮水平低于LH（0.1 ng/ml）单独刺激的水平。虽然IGF-I协同增强LH刺激雄酮的产生，SCF没有改变LH刺激的雄酮的产生在IGF-I的存在或不存在。单独的干细胞因子对LH受体、星星、CYP 11 A和3 β-HSD mRNA表达无影响，但降低CYP 17 mRNA水平。单独使用胰岛素样生长因子-I对星星或CYP 17 mRNA表达无影响，但可增加LH受体、CYP 11 A和3 β-HSD mRNA水平。SCF和IGF-I联合使用可增加所有5种mRNA的表达。这些数据支持IGF-I和SCF是TC分化的重要调节因子的结论。
The signal initiating ovarian theca cell (TC) differentiation is gonadotropin independent because theca precursor cells do not contain LH receptors. Previously we demonstrated that preantral follicles produce paracrine TC differentiating factors that promote androgen production by an LH-independent mechanism. This study tested the effects of two granulosa cell-produced peptides, insulin-like growth factor-I (IGF-I) and stem cell factor (SCF), on TC differentiation and androgen production. Neutralizing antibodies to either IGF-I or SCF blocked the stimulatory effects of follicle-conditioned medium on TC precursor differentiation more than 90%. The TC isolated from the ovaries of hypophysectomized immature rats by percoll gradient centrifugation were cultured (48 h) with and without SCF (0-100 ng/ ml) and ICF-I (0-100 ng/ml) to test their effects on TC differentiation. Androsterone in the medium was measured by RIA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein (StAR), CYP11A, CYP17, and 3 beta -hydroxysteroid dehydrogenase (3 beta -HSD) mRNAs were measured by specific reverse transcriptase polymerase chain reaction assays. Stem cell factor or IGF-I alone did not stimulate androsterone production but in combination caused a concentration-dependent increase in androsterone levels. Maximum androsterone levels were less than those stimulated by LH (0.1 ng/ml) alone. Although IGF-I synergistically augmented LH stimulation of androsterone production, SCF did not alter LH-stimulated androsterone production in the presence or absence of IGF-I. Stem cell factor alone had no effect on LH receptor, StAR, CYP11A, and 3 beta -HSD mRNA expression but decreased CYP17 mRNA levels. Insulin-like growth factor-I alone had no effect on StAR or CYP17 mRNA expression but increased LH receptor, CYP11A, and 3 beta -HSD mRNA levels. In combination, SCF plus IGF-I increased the expression of all five mRNAs. These data support the conclusion that IGF-I and SCF are important regulators of TC differentiation.