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

虽然促性腺激素在卵泡发生中的关键作用仍然存在，但局部因素在调节卵泡发生中的重要性已经被认识到。我们研究了包括激活素在内的局部因素调节卵泡发生的机制。使用DES诱导的幼鼠颗粒细胞。颗粒细胞在培养过程中激活素-A的分泌增加，但FSH抑制这种增加。推测这种抑制是通过cAMP/激酶A途径实现的，因为8-溴-cAMP抑制激活素-A分泌的方式与FSH相同。IGF-I增加FSH诱导的促黄体生成素受体基因的表达。提示IGF-I改变了黄体生成素受体基因转录速率，但延长了半衰期，从而改变了黄体生成素受体基因的稳定性。培养5d后，PRL抑制FSH诱导的促黄体生成素受体的表达。PRL不影响黄体生成素受体基因转录。提示催乳素的作用是通过改变黄体生成素受体基因的稳定性来实现的。我们在颗粒细胞中检测到肾上腺髓质素基因的表达。FSH抑制肾上腺髓质素的表达，hCG增强FSH的作用。8-溴-c-AMP抑制肾上腺髓质素的表达，而PMA对肾上腺髓质素的表达无影响。这些数据表明，促性腺激素介导的颗粒细胞分化与抑制肾上腺髓质素的表达有关，这是通过cAMP依赖的机制实现的。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发挥局部调节作用。未成熟小鼠卵母细胞-颗粒膜细胞复合体通过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，在卵母细胞-颗粒细胞复合体中，雄烯二酮和雌二醇的分泌低于可检测的限度。这些结果表明，包括激活素在内的许多生长因子调节卵泡的发生。

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.