THE EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON FOLLICLE-STIMULATING HORMONE-INDUCED DIFFERENTIATION OF CULTURED RAT GRANULOSA-CELLS
THE EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON FOLLICLE-STIMULATING HORMONE-INDUCED DIFFERENTIATION OF CULTURED RAT GRANULOSA-CELLS
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DOI：
10.1210/endo-120-2-512
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发表时间：
1987-02-01
期刊：
影响因子：
4.8
通讯作者：
SCHOMBERG, DW
中科院分区：
文献类型：
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作者：
DODSON, WC;SCHOMBERG, DW
生长因子贝内证实能调节培养的卵巢颗粒细胞的分化。转化生长因子（TGF）是一类能够可逆诱导正常细胞非贴壁依赖性生长的多肽生长因子。表皮生长因子（EGF），其与TGF α具有显著的结构同源性，已经显示在体外调节颗粒细胞的分化。类似地，TGF β.已发现TGFB（TGFB）与卵巢卵泡液中的Escherichia bin具有显著的结构同源性。为了检查TGFB是否可能影响颗粒细胞的生长或分化，将大鼠颗粒细胞在含有胰岛素的无血清培养基中培养长达3天，在存在或不存在FSH的情况下，加入不同浓度的TGFB。TGFB引起FSH刺激的LH/hCG受体结合的剂量依赖性增加，但在没有FSH的情况下对结合没有影响; TGFB（10.0ng/ml）进一步增加FSH刺激的LH/hCG受体结合48 ± 1.5ng/ml。8%（P < 0.02）。TGFB（1.0-10.0 ng/ml）使FSH刺激的孕酮分泌增加2- 3倍（P < 0.02）。相反，EGF（10.0ng/ml）使FSH刺激的LH/hCG受体结合降低93 ± 1.0ng/ml。1%（P < 0.02）。无论是FSH刺激的细胞内或细胞外cAMP的积累受到TGFB治疗。然而，EGF（10.0 ng/ml）减少细胞外和细胞内FSH刺激的cAMP积累在48和72小时的文化。TGFB对培养物蛋白质和DNA含量无显著影响。这些结果表明：1）TGFB可能通过不进一步增加细胞净cAMP积累的机制增强FSH刺激的LH受体诱导和类固醇生成; 2）TGFB和EGF对促性腺激素依赖性分化具有相反的作用; 3）TGFB/抑制素基因家族的产物可能具有自分泌或旁分泌调节颗粒细胞分化的能力。
Growth factors have bene shown to modulate differentiation of cultured ovarian granulosa cells. Transforming growth factors (TGFs) constitute a family of polypeptide growth factors capable of reversibly inducing anchorage-independent growth in normal cells. Epidermal growth factor (EGF), which has significant structural homology with TGF .alpha., has been shown to modulate differentiation of granulosa cells in vitro. Similarly, TGF.beta. (TGFB) has been found to have significant structural homology with ovarian follicular fluid inhibin. To examine whether TGFB might affect granulosa cell growth or differentiation, rat granulosa cells were cultured in serum-free medium containing insulin for up to 3 days with varying concentrations of TGFB in the presence or absence of FSH. TGFB caused a dose-dependent increase in FSH-stimulated LH/hCG receptor binding, but had no effect on binding in the absence of FSH; TGFB (10.0 ng/ml) further increased FSH-stimulated LH/hCG receptor binding by 48 .+-. 8% (P < 0.02). Similarly, FSH-stimulated progesterone production was increased by TGFB in a dose-dependent manner; TGFB (1.0-10.0 ng/ml) increased FSH-stimulated progesterone production 2- to 3-fold (P < 0.02). In contrast, EGF (10.0 ng/ml) decreased FSH-stimulated LH/hCG receptor binding by 93 .+-. 1% (P < 0.02). Neither FSH-stimulated intracellular nor extracellular cAMP accumulations were affected by TGFB treatment. However, EGF (10.0 ng/ml) diminished extracellular and intracellular FSH-stimulated cAMP accumulation at 48 and 72 h of culture. Culture protein and DNA content were not significantly affected by TGFB. These results suggest that 1) TGFB may enhance FSH-stimulated LH receptor induction and steroidogenesis by mechanisms that do not further increase net cellular cAMP accumulation; 2) TGFB and EGF can have opposite effects on gonadotropin-dependent differentiation; and 3) products of the TGFB/inhibitin gene family may have a capacity for autocrine or paracrine modulation of granulosa cell differentiation.