Hormone-induced receptor gene splicing: Enhanced expression of the growth factor type I follicle-stimulating hormone receptor motif in the developing mouse ovary as a new paradigm in growth regulation

Hormone-induced receptor gene splicing: Enhanced expression of the growth factor type I follicle-stimulating hormone receptor motif in the developing mouse ovary as a new paradigm in growth regulation
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DOI:
10.1210/en.142.1.381
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发表时间:
2001-01-01
期刊:
影响因子:
4.8
通讯作者:
Sairam, MR
Sairam, MR
中科院分区:
医学2区
文献类型:
--
作者:
Babu, PS;Danilovich, N;Sairam, MR

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卵泡生长过程中FSH受体的获得及其与信号通路的偶联是卵泡发育和优势的关键事件。然而,关于FSH受体参与激素作用的促生长阶段的确切性质知之甚少。为了研究一种新发现的选择性剪接生长因子1型受体(命名为FSH-R3)的激素调节,我们研究了成年小鼠中的表达和PMSG治疗对未成熟小鼠卵巢的影响。使用RT-PCR和基于已建立的绵羊卵巢转录本的引物,FSH-RB信息的一部分仅在野生型(+/+)小鼠卵巢中扩增,而在FSH-R敲除(-/-)小鼠卵巢中不扩增。使用FSH-R1(G(s)-偶联)和FSH-R3的3 '端特异性引物的半定量RT-PCR表明,当PMSG诱导卵泡生长时,后者的表达水平更高。利用FSH R3特异性肽IgG,通过Western blotting检测到FSH R3蛋白在成年小鼠卵巢提取物中的表达,并定位于成熟卵泡的颗粒细胞膜上。在未成熟的小鼠中,在PMSC给药后以时间依赖性方式增加的FSH-RS蛋白水平也仅位于大卵泡的颗粒细胞膜上。结果首次揭示了FSH在发育和周期小鼠卵巢中不同生长促进受体的表达。这些观察结果为卵巢功能的控制引入了一种新的模式。
The acquisition of FSH receptor(s) during follicular growth and their coupling to signaling pathways are key events in follicular development and dominance. However, little is known about the precise nature of the FSH receptor(s) involved in the growth-promoting phases of hormone action. To investigate the hormonal regulation of a newly discovered, alternatively spliced, growth factor type 1 receptor (designated FSH-R3) for the hormone, we examined expression in the adult mouse and the effect of PMSG treatment in the immature mouse ovary. Using RT-PCR and primers based on the established sheep ovarian transcript, a part of the FSH-RB message was amplified only in wild-type (+/+), but not in the FSH-R knockout (-/-), mouse ovary. Semiquantitative RT-PCR using 3'-end primers specific for FSH-R1 (G(s)-coupled) and FSH-R3 indicated expression levels of the latter to be higher when follicular growth was induced by PMSG. Using FSH-R3-specific peptide IgG, FSH-R3 protein was detected by Western blotting in extracts of adult mouse ovary and was localized in granulosa cell membrane of mature follicles. In the immature mouse, levels of FSH-RS protein that increased after PMSC administration in a time-dependent manner were also localized only on granulosa cell membranes of large follicles. The results reveal for the first time the expression of a different growth-promoting receptor for FSH in the developing and cycling mouse ovary. These observations introduce a new paradigm in the control of ovarian function.