Commercial hMG drugs are marketed for the treatment of infertility and consist of highly purified hormones acting on receptors expressed in target gonadal cells. Menopur^® and Meriofert^® are combined preparation of FSH and hCG and are compared in vitro herein. To this purpose, the molecular composition of the two drugs was analyzed by immunoassay. The formation of FSH receptor and LH/hCG receptor (FSHR; LHCGR) heteromer, intracellular Ca²⁺ and cAMP activation, β-arrestin 2 recruitment and the synthesis of progesterone and estradiol were evaluated in transfected HEK293 and human primary granulosa lutein cells treated by drugs administered within the pg-mg/ml concentration range. Molecular characterization revealed that Meriofert^® has a higher FSH:hCG ratio than Menopur^® which, in turn, displays the presence of LH molecules. While both drugs induced similar FSHR-LHCGR heteromeric formations and intracellular Ca²⁺ increase, Meriofert^® had a higher potency than Menopur^® in inducing a cAMP increase. Moreover, Meriofert^® revealed a higher potency than Menopur^® in recruiting β-arrestin 2, likely due to different FSH content modulating the tridimensional structure of FSHR-LHCGR-β-arrestin 2 complexes, as evidenced by a decrease in bioluminescence resonance energy transfer signal. This drug-specific activation of intracellular signaling pathways is consistent with the molecular composition of these preparations and impacts downstream progesterone and estradiol production, with Menopur^® more potent than Meriofert^® in inducing the synthesis of both the steroids. These findings are suggestive of distinct in-vivo activities of these preparations, but require cautious interpretation and further validation from clinical studies.

中文翻译：

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两种人类更年期促性腺激素 (hMG) 制剂在体外显示不同的早期信号

市售的 hMG 药物用于治疗不孕症，由高度纯化的激素组成，这些激素作用于靶标性腺细胞中表达的受体。Menopur ^®和 Meriofert ^®是 FSH 和 hCG 的组合制剂，并在本文中进行了体外比较。为此，通过免疫测定分析了两种药物的分子组成。FSH 受体和 LH/hCG 受体（FSHR；LHCGR）异聚体的形成、细胞内 Ca ²⁺和 cAMP 激活、β-抑制蛋白 2 募集以及黄体酮和雌二醇的合成在转染的 HEK293 和人原代颗粒叶黄素细胞中进行了评估在 pg-mg/ml 浓度范围内给药的药物。分子表征表明，Meriofert^®具有比 Menopur ^®更高的 FSH:hCG 比率，这反过来显示 LH 分子的存在。虽然这两种药物引起类似FSHR-LHCGR异聚形成和细胞内Ca ²⁺增加，Meriofert ^®有超过Menopur更高的效力^®在诱导的cAMP增加。此外，Meriofert ^®显示出比 Menopur ^®更高的效力在招募 β-arrestin 2 时，可能是由于不同的 FSH 含量调节了 FSHR-LHCGR-β-arrestin 2 复合物的三维结构，正如生物发光共振能量转移信号的减少所证明的那样。这个特定药物的细胞内信号途径的激活是用这些制剂和影响的分子组成下游孕酮和雌二醇生产一致，Menopur ^®比Meriofert更有效^®在诱导两种类固醇的合成。这些发现表明这些制剂具有不同的体内活性，但需要谨慎的解释和临床研究的进一步验证。