Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary.
Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary.
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DOI：
10.1210/mend.11.13.0032
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发表时间：
1997-12
影响因子：
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通讯作者：
Jian Zhou;T. Kumar;M. Matzuk;C. Bondy
中科院分区：
文献类型：
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作者：
Jian Zhou;T. Kumar;M. Matzuk;C. Bondy
目前的研究表明，胰岛素样生长因子I（IGF-I）和FSH受体（FSHR）的mRNA选择性共表达在一个子集的健康出现在小鼠卵巢卵泡，无论周期阶段。芳香化酶基因表达是FSH作用的主要标志，仅在IGF-I/FSHR阳性卵泡中发现，表明这些卵泡是健康的促性腺激素反应性卵泡。鉴于FSHR和IGF-I的显著共表达，我们假设FSH负责卵泡IGF-I的表达。然而，我们发现，颗粒细胞IGF-I mRNA水平在垂体切除（+/-PMSG）或FSH基因敲除小鼠中没有降低，表明FSH在调节颗粒细胞IGF-I基因表达中没有主要作用。为了检验IGF-I调节FSHR基因表达的备择假设，我们研究了IGF-I基因敲除小鼠的卵巢。与野生型小鼠相比，纯合子IGF-I敲除小鼠卵巢中FSHR mRNA显著降低，并通过外源性IGF-I治疗恢复至对照值。IGF-I基因敲除卵巢中FSHR基因表达减少的功能意义由芳香化酶表达减少和卵泡在早期窦期后不能正常发育而提出。事实上，IGF-I敲除和FSH敲除卵巢在卵泡发育停滞方面非常相似。总之，我们已经证明，IGF-I和FSHR选择性共表达在健康，生长的小鼠卵泡，FSH不影响IGF-I的表达，但IGF-I增强颗粒细胞FSHR的表达。这些数据表明，卵巢IGF-I的表达通过增加FSHR的表达来增强颗粒细胞FSH的反应性。
The present study shows that insulin-like growth factor I (IGF-I) and FSH receptor (FSHR) mRNAs are selectively coexpressed in a subset of healthy-appearing follicles in murine ovaries, irrespective of cycle stage. Aromatase gene expression, a prime marker for FSH effect, is found only in IGF-I/FSHR-positive follicles, showing that these are healthy, gonadotropin-responsive follicles. Given the striking coexpression of FSHR and IGF-I, we hypothesized that FSH was responsible for follicular IGF-I expression. We found, however, that granulosa cell IGF-I mRNA levels are not reduced in hypophysectomized (+/-PMSG) or FSH knockout mice, indicating that FSH does not have a major role in regulation of granulosa cell IGF-I gene expression. To test the alternative hypothesis that IGF-I regulates FSHR gene expression, we studied ovaries from IGF-I knockout mice. FSHR mRNA was significantly reduced in ovaries from homozygous IGF-I knockout compared with wild type mice and was restored to control values by exogenous IGF-I treatment. The functional significance of the reduced FSHR gene expression in IGF-I knockout ovaries is suggested by reduced aromatase expression and by the failure of their follicles to develop normally beyond the early antral stage. In fact, IGF-I knockout and FSH knockout ovaries appear very similar in terms of arrested follicular development. In summary, we have shown that IGF-I and FSHR are selectively coexpressed in healthy, growing murine follicles and that FSH does not affect IGF-I expression but that IGF-I augments granulosa cell FSHR expression. These data suggest that ovarian IGF-I expression serves to enhance granulosa cell FSH responsiveness by augmenting FSHR expression.