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Growth Hormone and Reproduction: Lessons Learned From Animal Models and Clinical Trials

机译:生长激素和生殖:从动物模型和临床试验中学到的教训

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摘要

Growth Hormone (GH) has been considered as a therapeutic option to increase the number of growing follicles during Assisted Reproductive Technology (ART) for more than 30 years. In this review the biological rationale for therapeutic GH usage is explained through evidence in animal models, aiming to put this into a clinical context. First, we explain the GH—Insulin like Growth Factor (IGF)-1—gonadal axis and its role in reproduction. Evidence suggests that GH can stimulate the secretion of IGF1 not only in the liver but also in the peripheral target structures, including the ovary. Moreover, IGF-1 can be secreted locally under the influence of stimuli other than GH. In the case of the ovary, steroid hormones, gonadotropins or the combination of both seems to be involved. Even more interesting, the ovary itself can secret GH locally and exert a paracrine action modulating the intracellular signaling pathway of GH, i.e., not by the systemic pathway where GH binds to the extracellular domain of the GH receptor. Finally, these aspects from animal models are put into clinical perspective by discussing results and shortcomings of studies and meta-analyses in order to put forth the state-of-the-art rationale for therapeutic GH usage in modern ART.
机译:生长激素(GH)被认为是30多年来在辅助生殖技术(ART)期间增加正在生长的卵泡数量的治疗选择。在这篇综述中,通过动物模型中的证据解释了治疗性GH的生物学原理,旨在将其用于临床。首先,我们解释GH-胰岛素样生长因子(IGF)-1-性腺轴及其在生殖中的作用。有证据表明,GH不仅可以刺激肝脏中IGF1的分泌,而且还可以刺激包括卵巢在内的外周靶结构的分泌。而且,IGF-1可以在GH以外的刺激的影响下局部分泌。就卵巢而言,似乎涉及类固醇激素,促性腺激素或两者的结合。甚至更有趣的是,卵巢本身可以局部分泌GH并发挥旁分泌作用调节GH的细胞内信号传导途径,即,不是通过GH结合至GH受体的细胞外结构域的全身途径。最后,通过讨论研究和荟萃分析的结果和不足,将动物模型的这些方面纳入临床视野,以提出现代ART中治疗性GH使用的最新原理。

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