THE EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II ON ESTRADIOL PRODUCTION BY GRANULOSA-CELLS OF POLYCYSTIC OVARIES
THE EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II ON ESTRADIOL PRODUCTION BY GRANULOSA-CELLS OF POLYCYSTIC OVARIES
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DOI：
10.1210/jcem-70-4-894
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发表时间：
1990-04-01
影响因子：
5.8
通讯作者：
CHANG, RJ
中科院分区：
文献类型：
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作者：
ERICKSON, GF;MAGOFFIN, DA;CHANG, RJ
本研究的目的是探讨胰岛素样生长因子（IGFs）对多囊卵巢病（PCO）患者卵巢颗粒细胞雌二醇（E2）产生的影响。颗粒细胞，从三个PCO患者的卵巢分离，培养在无血清培养基中含有单独的雄烯二酮（10-7 M）或雄烯二酮加分级剂量的FSH，IGF-I，IGF-II，和/或胰岛素。在培养期结束时（2、4或6天），通过RIA测量培养基中的E2水平。每例患者的结果相似，因此汇总了数据。在6天的时间过程实验中，对照（未处理）细胞在2天时产生相对高水平的E2;然而，此后未检测到E2。FSH（30 ng/mL）刺激E2生产4倍，在2天，但FSH的刺激作用在培养过程中没有持续。30 ng/mL的IGF-I模拟FSH的作用。FSH和IGF-I联合治疗导致E2产生协同增加（第2、4和6天分别为3、13和33倍）。剂量-反应研究显示FSH和IGF-I以剂量依赖性方式刺激E2产生（FSH和IGF-I的ED 50为1.1 ± 0.5）。0.3和7.6 .+-。7.2 ng/mL）。在最大有效剂量的FSH（30 ng/mL）存在下，细胞似乎对IGF-I变得更敏感（IGF-I加FSH的ED 50，1.09 ± 0.01）。0.29 ng/mL）;然而，该效应不显著（P = 0.086）。在存在最大有效剂量的IGF-I（30 ng/mL）的情况下，FSH对E2产生的刺激作用显著增强，但IGF-I没有显著（P = 0.85）改变FSH的效力（FSH加IGF-I的ED 50，1.07 ± 0.05）。2.3 ng/mL）。在0.1-100 ng/mL的浓度范围内用IGF-II处理对对照或FSH刺激的E2产生没有影响。单独或与FSH一起用胰岛素治疗增加了E2的水平，但仅在最高测试剂量（0.3-10 μ g/mL）下观察到胰岛素作用。PCO颗粒细胞的这些体外实验结果表明：1）生理浓度的IGF-I在刺激E2产生方面与FSH一样有效; 2）IGF-I和FSH协同作用以控制E2产生水平; 3）胰岛素或IGF-II未观察到这种协同作用。
The objective of this work was to examine the effects of insulin-like growth factors (IGFs) on estradiol (E2) production by granulosa cells obtained from ovaries of patients with polycystic ovary disease (PCO). Granulosa cells, isolated from ovaries of three PCO patients, were cultured in serum-free medium containing either androstenedione alone (10-7 M) or androstenedione plus graded doses of FSH, IGF-I, IGF-II, and/or insulin. At the end of the culture period (2, 4, or 6 days) E2 levels in the medium were measured by RIA. The results from each patient were similar, and therefore, the data were pooled. In the 6-day time-course experiments, the control (untreated) cells produced relatively high levels of E2 at 2 days; however, none was detected thereafter. Treatment with FSH (30 ng/mL) stimulated E2 production 4-fold at 2 days, but the stimulatory effects of FSH were not sustained during culture. IGF-I at 30 ng/mL mimicked the effects of FSH. Concomitant treatment with FSH and IGF-I caused synergistic increases in E2 production (3-, 13-, and 33-fold at 2, 4, and 6 days, respectively). Dose-response studies revealed that FSH and IGF-I stimulated E2 production in a dose-dependent fashion (ED50 of FSH and IGF-I, were 1.1 .+-. 0.3 and 7.6 .+-. 7.2 ng/mL, respectively). In the presence of a maximally effective dose of FSH (30 ng/mL), the cells appeared to become more responsive to IGF-I (ED50 of IGF-I plus FSH, 1.09 .+-. 0.29 ng/mL); however, this effect was not significant (P = 0.086). In the presence of a maximally effective dose of IGF-I (30 ng/mL), the stimulatory effect of FSH on E2 production was dramatically amplified, but the IGF-I did not significantly (P = 0.85) change the potency of FSH (ED50 of FSH plus IGF-I, 1.07 .+-. 2.3 ng/mL). Treatment with IGF-II over the concentration range of 0.1-100 ng/mL had no effect on either control or FSH-stimulated E2 production. Treatment with insulin, either alone or together with FSH, increased the levels of E2, but the insulin effects were seen only at the highest doses tested (0.3-10 .mu.g/mL). The results in these in vitro experiments with PCO granulosa cells indicate that 1) physiological concentrations of IGF-I are as effective as FSH in stimulating E2 production; 2) IGF-I and FSH act synergistically to control the level of E2 production; and 3) this synergy was not observed with insulin or IGF-II.