Yamamoto Yoji, Yoshizaki Goro, Takeuchi Toshio, Soyano Kiyoshi, Patiño Reynaldo
Department of Marine Biosciences, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan.
Gen Comp Endocrinol. 2008 Feb 1;155(3):789-95. doi: 10.1016/j.ygcen.2007.09.011. Epub 2007 Sep 19.
Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18alpha-glycyrrhetinic acid (alpha-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20beta-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption.
硬骨鱼卵母细胞的减数分裂恢复由成熟诱导激素（MIH）诱导。卵母细胞对MIH的敏感性，也称为卵母细胞成熟能力（OMC），由促黄体生成素（LH）通过尚未完全了解的机制诱导。先前对香鱼（Plecoglossus altivelis）的一项研究表明，卵母细胞与其周围颗粒细胞之间存在功能性异源间隙连接（GJ）。本研究的目的是确定卵巢GJ和蛋白激酶A（PKA）在OMC获得过程中的作用。我们研究了特异性GJ抑制剂羧苄青霉素（CBX）和18α-甘草次酸（α-GA）对LH-（人绒毛膜促性腺激素）依赖的OMC获得以及对MIH-（17,20β-二羟基-4-孕烯-3-酮）依赖的减数分裂恢复的影响；在hCG依赖的OMC获得过程中测量卵巢卵泡的cAMP含量；并确定PK激活剂和抑制剂对hCG依赖的OMC的影响。在hCG依赖的OMC获得过程中，卵泡cAMP的产生增加。GJ抑制剂和PKA抑制剂H8-二盐酸盐，但不是PKC抑制剂GF109203X，以剂量依赖的方式抑制hCG依赖的OMC获得。PKA激活剂福斯可林诱导OMC的效力与hCG相似。与先前对硬骨鱼的观察不同，在硬骨鱼中异源GJ的破坏要么阻断要么刺激减数分裂恢复，用GJ抑制剂处理对香鱼成熟卵泡中MIH依赖的减数分裂恢复没有影响。这些观察结果表明，卵巢GJ对于LH依赖的OMC获得是必不可少的，但对于MIH依赖的减数分裂恢复不是必需的，并且LH对OMC的刺激是由cAMP依赖的PKA介导的。它们也与以下观点一致，即激素调节的减数分裂恢复需要GJ介导的信号（正或负）与卵母细胞成熟准备之间的精确平衡。
