促性腺激素释放激素激动剂降调对垂体内外的影响

摘要

降调是促激素下调自身的受体以调节靶组织对激素的反应性,是促激素调节其自身作用的机制之一.除受体的升调和降调外,促激素还可通过自分泌/旁分泌、激素的异质性来调节自身的作用.降调的机制是通过受体与调节亚单位G蛋白解耦联、受体内在化进入细胞、以及腺苷酸环化酶的调节和催化亚单位解耦联3种途径来实现的.降调对卵泡刺激素(FSH)和黄体生成素(LH)的直接作用是使40％～60％的FSH分泌受到抑制,而90％的LH分泌受到抑制,目的是抑制过早内源性LH峰.降调对FSH、LH旁分泌调节的作用需要通过FSH和LH发挥作用,旁分泌调节因子本身并没有促使卵泡发育的作用.由于类固醇激素的负反馈是通过下丘脑垂体发挥作用,而降调是在促性腺激素释放激素(GnRH)的受体水平,因此取消了类固醇激素正常的正负反馈.由于卵巢颗粒细胞、膜细胞、黄体细胞均有GnRH受体,理论上推测GnRH对卵巢可能有直接作用.动物实验及体外试验均提示GnRH对卵巢颗粒细胞有直接作用,体现在类固醇的合成和卵泡的发育两方面.因此,促性腺激素释放激素激动剂(GnRH-a)提高妊娠率的作用除了来自于抑制过早LH峰,降低过高LH的不利作用外,还可能来自GnRH-a对卵泡发育、卵母细胞成熟、子宫内膜的容受性等直接作用,但目前的研究方法尚无法证实.%Downregulation means regulating ovarian responsivity to hormone through the downregulation of hormone receptors, which is one of the mechanism of gonadotropins regulating its own function. Except for upregulation and downregulation of the receptors, autoregulation could also be realized by autocrine, paracrine secretion and hormone heterogeneity. The achievement of downregulation is through three pathways: decoupling of receptor and regulatory subunit Oprotein; receptor internalization; the regulation of c-AMP and decoupling of catalytic subunit.40%-60% of follicle-stimulating hormone (FSH) secretion is repressed by the immediate action of downregulation,while 90% luteinizing hormone (LH) could be repressed, so downregulation is used to prevent the premature LH surges. Regulation of paracrine secretion by downregulation requires the involvement of FSH and LH and regulatory factors of paracrine secretion have no effect on the promotion of follicular development. The negative feedback of steroid hormone is through the level of hypothalamus and pituitary, while downregulation functions at the level of the gonadotropin-releasing hormone (GnRH) receptors, so the normal positive and negative feedbacks are cancelled by downregulation.There exist GnRH receptors in granulosa cells, theca cells and luteal cells, so it could be presumed theoretically that GnRH may have direct effects on ovary. Both animal experiments and in vitro studiessuggest that GnRH may have a direct action on ovarian granulosa cells through interfering steroid synthesis and follicular development. So except for preventing the premature LH surges and decreasing the detrimental effect of high LH, the effect of GnRH agonist-induced down-regulation increasing pregnancy rate may be also through the immediate action on follicular development, oocyte maturation and endometrial receptivity, but no confirmation has been made by the existing evidence.