Comparative pharmacology of a new recombinant FSH expressed by a human cell line

被引：36

作者：

Koechling, Wolfgang ^{[1
]}

Plaksin, Daniel ^{[2
]}

Croston, Glenn E. ^{[3
]}

Jeppesen, Janni V. ^{[4
,5
]}

Macklon, Kirsten T. ^{[4
,5
]}

Andersen, Claus Yding ^{[4
,5
]}

机构：

[1] Ferring Pharmaceut AS, Copenhagen, Denmark

[2] Ferring Pharmaceut, Biotechnol Gen Israel Ltd, Kiryat Malachi, Israel

[3] Croston Consulting, San Diego, CA USA

[4] Copenhagen Univ Hosp, Rigshosp, Lab Reprod Biol, Dept Fertil,Juliane Marie Ctr, Copenhagen, Denmark

[5] Univ Copenhagen, Copenhagen, Denmark

来源：

ENDOCRINE CONNECTIONS | 2017年 / 6卷 / 05期

关键词：

follicle-stimulating hormone; follitropin delta; gonadotropin clearance; recombinant FSH; FSH glycosylation; FOLLICLE-STIMULATING-HORMONE; INDUCED GENE-REGULATION; ANTI-MULLERIAN HORMONE; ASIALOGLYCOPROTEIN RECEPTOR; GRANULOSA-CELLS; IVF PATIENTS; OVARIAN STIMULATION; GLYCOSYLATION; GLYCOPROTEINS; MODULATION;

D O I：

10.1530/EC-17-0067

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recombinant FSH proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in Chinese Hamster Ovary (CHO) cells and, more recently, follitropin delta expressed in the human cell line PER. C6. These recombinant FSH proteins have distinct glycosylation, and have distinct pharmacokinetic and pharmacodynamic profiles in women. Comparative experiments demonstrated that follitropin delta and follitropin alfa displayed the same in vitro potency at the human FSH receptor, but varied in their pharmacokinetics in mouse and rat. While follitropin delta clearance from serum depended in part on the hepatic asialoglycoprotein receptor (ASGPR), follitropin alfa clearance was unaffected by ASGPR inhibition in rat or genetic ablation in mice. The distinct properties of follitropin delta and follitropin alfa are likely to contribute to the differing pharmacokinetic and pharmacodynamic profiles observed in women and to influence their efficacy in therapeutic protocols for the treatment of infertility.

引用

页码：297 / 305

页数：9

共 38 条

[1] Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial [J].