Gene expression profiles of human granulosa cells treated with bioequivalent doses of corifollitropin alfa (CFA) or recombinant human follicle-stimulating hormone (recFSH)

Abstract

Using recombinant DNA technologies, a chimeric gene containing the coding sequences of follicle stimulating hormone (FSH) β-subunit and C-terminal peptide of the human chorionic gonadotrophin (hCG) β-subunit have been designed to generate a new gonadotrophin named corifollitropin alfa (CFA). CFA has longer elimination half-life and slower rate of absorption compared with FSH, which makes CFA a long-acting hormone employed as a substitute of the recombinant FSH (recFSH) in the controlled ovarian stimulation (COS). The purpose of this study is to compare the gene expression profiles elicited by bioequivalent doses of CFA or recFSH in primary cultures of human granulosa cells (hGCs). Gonadotrophins exert their functions by binding FSH receptors (FSHRs), activating signaling pathways that increase the cyclic adenosine monophosphate (cAMP) intracellular content. Bioequivalence has been defined as the dose/duration of gonadotrophin treatment able to promote the same amount of intracellular cAMP. hGCs were treated with different doses of either gonadotrophin and the cAMP was measured after different incubation times to establish the bioequivalence. Results obtained by comparing the bioequivalent treatments, showed that CFA is more effective than recFSH in inducing aromatase gene expression after 6 and 24 h from the initial stimulation in agreement with its long-acting characteristic.

摘要

应用DNA重组技术, 由包含编码序列的嵌合基因的卵泡刺激素的β亚单位和C肽端的人绒毛膜促性腺激素（hCG）的β亚单位形成一个新的促性腺激素, 叫做绒促卵泡素α（CFA）。与FSH相比, CFA具有较长的消除半衰期和较慢的吸收速度, 这使得CEA作为重组FSH（recFSH）在控制性促排卵（COS）中替代长效激素。本研究的目的是比较等效剂量的CFA或recFSH在人类颗粒细胞（hGCs）首代培养中的基因表达谱。促性腺激素通过结合FSH受体（FSHRs）发挥作用, 激活信号通路从而增加细胞内环磷酸腺苷（cAMP）的含量。生物等效性被定义为促性腺激素治疗的剂量/持续时间能够激发相同数量的细胞内cAMP。不同剂量的促性腺激素作用于hGCs, 并在不同潜伏期测定cAMP, 从而建立生物等效性。通过对生物等效处理的比较, 结果表明, 初始刺激6小时和24小时后, CFA诱导芳香化酶基因表达的效果优于recFSH, 符合CFA的长效特性。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Corifollitropin alfa
• recombinant FSH
• bioequivalence
• gonadotrophin
• aromatase

Acknowledgements

The authors thank Dr Valeria Moriondo for helping us to improve the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.