Behrman H R, Aten R F, Luborsky J L, Polan M L, Miller J G, Soodak L K
J Anim Sci. 1986;62 Suppl 2:14-24. doi: 10.1093/ansci/62.2.14.
The evidence for a paracrine, progonadotropic role of adenosine in ovarian cells is summarized along with a capsule review of the origin and mechanisms of release and action of adenosine in other tissues. Briefly, adenosine markedly amplified rat and human luteal cell cyclic AMP and progesterone accumulation in the presence, but not the absence, of LH. The site of action of adenosine was found to be intracellular, linked to its phosphorylation, which resulted in increased levels of ATP. In rat luteal cells, adenosine blocked the acute antigonadotropic (luteolytic) action of PGF2 alpha. In the follicle, adenosine release from granulosal cells appeared to be stimulated by FSH. Adenosine and a nonmetabolized adenosine analog, augmented FSH-dependent inhibition of oocyte maturation in the presence or absence of an adenosine transport inhibitor. Inhibition of oocyte maturation by adenosine thus appears to be mediated by extracellular purinergic receptors. Paracrine, antigonadotropic agents also appear to regulate ovarian function. For example, GnRH elicits antigonadotropic activity in rat granulosal and luteal cells. We describe a novel, GnRH-like, ovarian hormone (GLOH) which may be the physiological ligand whose action GnRH mimics in rat ovarian cells. This protein was shown to be distinctly different from GnRH and a variety of other cyclic and noncyclic peptides. PGF2 alpha is a well known leutolytic agent and a summary of the antigonadotropic mechanism of PGF2 alpha action in rat luteal cells is presented. In these cells, the action of GnRH (or possibly the GnRH-like protein) and PGF2 alpha are mediated by separate membrane receptors but they appeared to share the same intracellular second messenger. Evidence for a role of products of phosphoinositol as a mediator of these antigonadotropic agents is summarized. We suggest that the ultimate mediator of antigonadotropic agents is Ca2+ which is released in the luteal cell in response to the intracellular mediator of antigonadotropic agents. For example, pharmacological agents which increase intracellular levels of Ca2+, mimicked the antigonadotropic action of GnRH and PGF2 alpha in rat luteal cells. Also, Ca2+ directly inhibited LH-sensitive adenylate cyclase activity in isolated luteal membranes, a paradigm in which GnRH and PGF2 alpha were inactive. The mechanism of Ca2+ action appeared to be linked to interference with GTP activation of adenylate cyclase. However, removal of extracellular Ca2+ did not abrogate the action of either GnRH or PGF2 alpha.(ABSTRACT TRUNCATED AT 400 WORDS)
本文总结了腺苷在卵巢细胞中旁分泌、促性腺作用的证据，并简要回顾了腺苷在其他组织中的起源、释放机制及作用机制。简而言之，在促黄体生成素（LH）存在而非缺失的情况下，腺苷可显著增强大鼠和人黄体细胞中环磷酸腺苷（cAMP）的积累及孕酮的生成。腺苷的作用位点位于细胞内，与其磷酸化相关，磷酸化导致三磷酸腺苷（ATP）水平升高。在大鼠黄体细胞中，腺苷可阻断前列腺素F2α（PGF2α）的急性抗促性腺（溶黄体）作用。在卵泡中，促卵泡生成素（FSH）似乎可刺激颗粒细胞释放腺苷。在存在或不存在腺苷转运抑制剂的情况下，腺苷及一种非代谢性腺苷类似物均可增强FSH对卵母细胞成熟的抑制作用。因此，腺苷对卵母细胞成熟的抑制作用似乎是由细胞外嘌呤能受体介导的。旁分泌抗促性腺因子似乎也参与调节卵巢功能。例如，促性腺激素释放激素（GnRH）可在大鼠颗粒细胞和黄体细胞中引发抗促性腺活性。我们描述了一种新型的、类似GnRH的卵巢激素（GLOH），它可能是GnRH在大鼠卵巢细胞中模拟作用的生理配体。该蛋白与GnRH及多种其他环状和非环状肽明显不同。PGF2α是一种众所周知的溶黄体因子，本文总结了其在大鼠黄体细胞中抗促性腺作用的机制。在这些细胞中，GnRH（或可能是类似GnRH的蛋白）和PGF2α的作用由不同的膜受体介导，但它们似乎共享相同的细胞内第二信使。本文总结了磷酸肌醇产物作为这些抗促性腺因子介质作用的证据。我们认为抗促性腺因子的最终介质是钙离子（Ca2+），它在黄体细胞中因抗促性腺因子的细胞内介质而释放。例如，增加细胞内Ca2+水平的药物可模拟GnRH和PGF2α在大鼠黄体细胞中的抗促性腺作用。此外，Ca2+可直接抑制分离的黄体细胞膜中对LH敏感的腺苷酸环化酶活性，而在该模型中GnRH和PGF2α无活性。Ca2+的作用机制似乎与干扰腺苷酸环化酶的鸟苷三磷酸（GTP）激活有关。然而，去除细胞外Ca2+并不能消除GnRH或PGF2α的作用。（摘要截取自400字）
