Pituitary and extrapituitary actions of gonadotrophin-releasing hormone and its analogues
Pituitary and extrapituitary actions of gonadotrophin-releasing hormone and its analogues
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DOI：
10.1093/humrep/14.suppl_1.194
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发表时间：
1999-09-01
影响因子：
6.1
通讯作者：
Diedrich, K
中科院分区：
文献类型：
--
作者：
Ortmann, O;Diedrich, K
下丘脑十肽促性腺激素释放激素（GnRH）与垂体促性腺激素细胞上的高亲和力受体结合，这些受体介导GnRH对促性腺激素分泌和合成的影响，GnRH受体与G（q）/G（11）偶联，G（q）/G（11）激活磷脂酶C。这种酶导致产生几种第二信使分子，其中，甘油二酯（DG）和肌醇1，4，5-三磷酸（IP 3）是至关重要的，DG导致蛋白激酶C的活化，IP 3从细胞内池释放Ca 2+，这两种事件导致促黄体生成激素（LH）和促卵泡激素（FSH）的分泌和合成，此外，GnRH信号转导途径的其它组分参与对GnRH的细胞应答，GnRH受体及其功能由GnRH本身或其它激素如卵巢类固醇调节。垂体促性腺激素细胞长期暴露于GnRH导致脱敏，从而抑制LW和FSH分泌。这种机制用于GnRH激动剂的临床应用，GnRH拮抗剂通过竞争性结合垂体GnRH受体发挥作用，除了GnRH的垂体作用外，在各种垂体外组织中也发现了十肽受体。本文报道了GnRH的卵巢作用，在大鼠卵巢中主要是抑制性的，在人类卵巢中GnRH受体的存在是有争议的，最近的报道已经证实了人类卵巢中存在GnRH受体的mRNA，然而，迄今为止，关于GnRH或其类似物的卵巢作用还没有达成共识。
The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to high affinity receptors on pituitary gonadotrophs, These receptors mediate the effects of GnRH on secretion and synthesis of gonadotrophins, The GnRH receptor is coupled to G(q)/G(11), which activates phospholipase C. This enzyme leads to the generation of several second messenger molecules, Among these, diacylglycerol (DG) and inositol 1,4,5-tris-phosphate (IP3) are critically important, DG leads to activation of protein kinase C and IP3 releases Ca2+ from intracellular pools, Both events result in secretion and synthesis of luteinizing hormone (LH) and follicle stimulating hormone (FSH), In addition, other components of the GnRH signal transduction pathway are involved in cellular responses to GnRH, GnRH receptors and their functions are regulated by GnRH itself or other hormones such as ovarian steroids, The prolonged exposure of pituitary gonadotrophs to GnRH leads to desensitization and consequently to suppressed LW and FSH secretion, This mechanism is employed for the clinical use of GnRH agonists, GnRH antagonists act by competitive binding to the pituitary GnRH receptors, Apart from the well-established pituitary actions of GnRH, receptors for the decapeptide have been demonstrated in a variety of extrapituitary tissues, Here we report on the ovarian actions of GnRH which are predominantly inhibitory in the rat ovary, In the human ovary the existence of GnRH receptors is controversial, Recent reports have demonstrated the mRNA for the GnRH receptor in the human ovary, However, to date there is no consensus on the ovarian actions of GnRH or its analogues.