Insulin-like growth factor-I as an amplifier of follicle-stimulating hormone action: studies on mechanism(s) and site(s) of action in cultured rat granulosa cells.
Insulin-like growth factor-I as an amplifier of follicle-stimulating hormone action: studies on mechanism(s) and site(s) of action in cultured rat granulosa cells.
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DOI：
10.1210/endo-122-4-1583
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发表时间：
1988-04
期刊：
影响因子：
4.8
通讯作者：
E. Adashi;C. Resnick;E. Hernández;J. V. May;M. Knecht;M. Svoboda;J. J. Wyk-J.
中科院分区：
文献类型：
--
作者：
E. Adashi;C. Resnick;E. Hernández;J. V. May;M. Knecht;M. Svoboda;J. J. Wyk-J.
卵巢颗粒细胞最近被证明是胰岛素样生长因子-I (IGF-I) 产生、接收和作用的场所。在很大程度上，IGF-I 的作用（在大鼠中）似乎取决于其与 FSH（颗粒细胞分化的主要促进剂）协同作用的能力。本文报道的体外研究的目的是阐明 IGF-I 放大 FSH 激素作用的细胞机制，特别强调假定的细胞内第二信使 cAMP 在这方面的潜在作用。用 IGF-I (50 ng/ml) 单独处理 72 小时后，在无血清条件下培养的大鼠颗粒细胞的基础 FSH 结合（115.7 +/- 2.1 fmol/mg 细胞蛋白）保持不变（107.1 +/- 1.0 fmol/mg 细胞蛋白）。相反，在IGF-I存在或不存在的情况下，与对照相比，用FSH (20 ng/ml)处理导致FSH结合能力（但不是亲和力）显着降低（P小于0.05）。 FSH 治疗导致毛喉素刺激的腺苷酸环化酶活性显着增加（10 +/- 1.7% [3H] ATP 转化为 [3H]cAMP），而同时用 IGF-I 治疗导致 FSH 作用增强 2.2 倍。事实证明，这种 IGF-I 效应具有剂量依赖性，表观中位有效剂量为 3.6 +/- 0.8 ng/ml，该浓度与其颗粒细胞受体结合亲和力一致。然而，值得注意的是，IGF-I 被证明能够增强 Bt2cAMP 刺激的孕酮积累，这表明 IGF-I 也可能作用于 cAMP 生成远端的位点。总而言之，这些和之前的研究表明，纳摩尔浓度的外源添加 IGF-I 可能与多个细胞位点的 FSH 转导信号相互作用，从而影响 FSH 作用的放大。
The ovarian granulosa cell has recently been shown to be a site of insulin-like growth factor-I (IGF-I) production, reception, and action. In large measure, IGF-I action (in the rat) appears contingent upon its ability to synergize with FSH, a major promoter of granulosa cell differentiation. It is the objective of the in vitro studies reported herein to elucidate the cellular mechanism(s) whereby IGF-I amplifies FSH hormonal action, placing special emphasis on the potential role of the putative intracellular second messenger cAMP in this regard. Basal FSH binding (115.7 +/- 2.1 fmol/mg cell protein) to rat granulosa cells cultured under serum-free conditions remained unchanged after 72 h of treatment with IGF-I (50 ng/ml) by itself (107.1 +/- 1.0 fmol/mg cell protein). In contrast, treatment with FSH (20 ng/ml) resulted in a significant (P less than 0.05) decrease in FSH binding capacity (but not affinity) relative to controls in either the absence or presence of IGF-I. Whereas treatment with FSH resulted in a substantial increase in forskolin-stimulatable adenylate cyclase activity (10 +/- 1.7% conversion of [3H] ATP to [3H]cAMP), concurrent treatment with IGF-I resulted in 2.2-fold enhancement of FSH action. This IGF-I effect proved dose dependent with an apparent median effective dose of 3.6 +/- 0.8 ng/ml, a concentration in keeping with its granulosa cell receptor binding affinity. Significantly, however, IGF-I proved capable of enhancing Bt2cAMP-stimulated progesterone accumulation suggesting that IGF-I may be also acting at site(s) distal to cAMP generation. Taken together, these and previous studies indicate that nanomolar concentrations of exogenously added IGF-I may be interacting with the FSH transduction signal at multiple cellular site(s) to effect amplification of FSH action.