In clinical practice, luteinizing hormone (LH) and chorionic gonadotropin (CG) are used as activators of the LH receptor, leading to the stimulation of gonadal steroidogenesis. However, high doses of gonadotropin preparations cause a number of side effects. Here we demonstrate that the pretreatment of male rats with TP03, an allosteric agonist of the LH receptor, at doses of 7.5–25 mg/kg significantly increases the testosterone production-stimulating effect of CG administered at a dose of 50 IU/rat, which is twice as low as that inducing a maximum steroidogenic effect. We assume that this is due to additivity of the CG and TP03 effects, as well as the potentiating effect of TP03 on CG signaling pathways. Three hours after CG administration to TP03-pretreated rats, the activation pattern of the genes of steroidogenic enzymes and LH receptor exhibits specific changes which mainly concern 3p-dehydrogenase gene expression. The obtained data indicate a prospectivity of TP03 and CG co-application allowing the effective dose of gonadotropin preparations to be reduced.

中文翻译：

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用变构促黄体激素受体激动剂预处理大鼠可增强绒毛膜促性腺激素诱导的睾酮生成刺激

在临床实践中，促黄体生成素 (LH) 和绒毛膜促性腺激素 (CG) 被用作 LH 受体的激活剂，从而刺激性腺类固醇生成。然而，高剂量的促性腺激素制剂会引起许多副作用。在这里，我们证明了用 7.5-25 mg/kg 剂量的 TPO3（一种 LH 受体的别构激动剂）预处理雄性大鼠，显着增加了以 50 IU/大鼠的剂量给药的 CG 的睾酮产生刺激作用。是诱导最大类固醇生成作用的两倍。我们假设这是由于 CG 和 TP03 效应的可加性，以及 TP03 对 CG 信号通路的增强作用。对经 TP03 预处理的大鼠施用 CG 后三小时，类固醇生成酶和 LH 受体基因的激活模式表现出特定的变化，主要与 3p-脱氢酶基因表达有关。获得的数据表明 TPO3 和 CG 共同应用的前景允许减少促性腺激素制剂的有效剂量。