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Investigation of mono-ovulatory mechanisms through the action of the inhibin/activin family

通过抑制素/激活素家族的作用研究单排卵机制

基本信息

批准号：
10470342
负责人：
IBUKI Yoshito
金额：
$ 4.03万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470342/
关键词：
Inhibin Activin Follistatin Folliculogenesis

项目摘要

The importance of local factors to modulate folliculogenesis has been recognized, although the key role of gonadotropins in folliculogenesis remains. We investigated the mechanisms through which local factors including activin modulated folliculogenesis.Granulosa cells from DES primed immature rats were used. The secretion of activin-A from granulosa cells increased during the culture but FSH suppressed this increase. It is suggested that this suppression occurs through cAMP/kinase A pathway because 8-Br-cAMP suppressed activin-A secretion in the same manner as FSH. IGF-I increased FSH-induced LH receptor mRNA. It is suggested that IGF-I changed the stability of LH receptor mRNA because the rate of LH receptor mRNA gene transcription was not changed but the half-life of LH receptor mRNA increased by IGF-I. PRL suppressed LH receptor expression induced by FSH after 5 days of culture. PRL did not affect LH receptor gene transcription. It was suggested that the effect of PRL was exerted by changing the stability of LH receptor mRNA. We detected adrenomedullin mRNA in granulosa cells. FSH suppressed the expression of adrenomedullin and hCG enhanced the effect of FSH. 8-Br-c AMP suppressed the expression of adrenomedullin but PMA did not have any effect on the expression. These data indicate that the differentiation of granulosa cells mediated by gonadotropins were associated with the suppression of adrenomedullin expression through a cAMP-dependent mechanism. Adrenomedullin may play a role in the process of granulosa cell differentiation as a local regulator through an autocrine/paracrine mechanism.The oocyte-granulosa-theca cell complex from immature mice secreted androstenedione by hCG and IR- inhibin and estradiol by activin-A. On the other hand, the secretion of androstenedione and estradiol was below detectable limits in the oocyte-granulosa cell complex.These results indicate that many growth factors including activin modulate folliculogenesis.

虽然促性腺激素在卵泡发生中的关键作用仍然存在，但局部因素对调节卵泡发生的重要性已经得到承认。我们研究了通过激活素等局部因素调节卵泡发生的机制。采用DES诱导的未成熟大鼠颗粒细胞。颗粒细胞的激活素a分泌在培养过程中增加，但FSH抑制了这种增加。这表明这种抑制是通过cAMP/激酶A途径发生的，因为8-Br-cAMP以与FSH相同的方式抑制activin-A的分泌。igf - 1增加fsh诱导的LH受体mRNA。提示IGF-I改变了LH受体mRNA的稳定性，因为IGF-I没有改变LH受体mRNA基因的转录速率，但增加了LH受体mRNA的半衰期。培养5天后，PRL抑制FSH诱导的LH受体表达。PRL不影响LH受体基因转录。提示PRL的作用可能是通过改变LH受体mRNA的稳定性来实现的。我们在颗粒细胞中检测肾上腺髓质素mRNA。FSH抑制肾上腺髓质素的表达，hCG增强FSH的作用。8-Br-c AMP抑制肾上腺髓质素的表达，而PMA对其表达无影响。这些数据表明，促性腺激素介导的颗粒细胞分化与通过camp依赖机制抑制肾上腺髓质素的表达有关。肾上腺髓质素可能通过自分泌/旁分泌机制在颗粒细胞分化过程中起局部调节作用。未成熟小鼠卵母细胞-颗粒-卵泡细胞复合物通过hCG分泌雄烯二酮，通过激活素a分泌IR-抑制素和雌二醇。另一方面，雄烯二酮和雌二醇的分泌在卵粒细胞复合体中低于检测限度。这些结果表明许多生长因子包括激活素调节卵泡发生。