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

Wolfgang Koechling; Daniel Plaksin; Glenn E. Croston; Janni V. Jeppesen; Kirsten T. Macklon; Claus Yding Andersen

doi:10.1530/EC-17-0067

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

Wolfgang Koechling^*, Daniel Plaksin, Glenn E. Croston, Janni V. Jeppesen, Kirsten T. Macklon, Claus Yding Andersen

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

11 Citationer (Scopus)

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Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Endocrine Connections
Vol/bind	6
Udgave nummer	5
Sider (fra-til)	297-305
ISSN	2049-3614
DOI	https://doi.org/10.1530/EC-17-0067
Status	Udgivet - 2017

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10.1530/EC-17-0067Licens: CC BY

297.fullForlagets udgivne version, 1,42 MBLicens: CC BY

Citationsformater

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title = "Comparative pharmacology of a new recombinant FSH expressed by a human cell line",

abstract = "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.",

keywords = "Follicle-stimulating hormone, Follitropin delta, FSH glycosylation, Gonadotropin clearance, Recombinant FSH",

author = "Wolfgang Koechling and Daniel Plaksin and Croston, {Glenn E.} and Jeppesen, {Janni V.} and Macklon, {Kirsten T.} and Andersen, {Claus Yding}",

year = "2017",

doi = "10.1530/EC-17-0067",

language = "English",

volume = "6",

pages = "297--305",

journal = "Endocrine Connections",

issn = "2049-3614",

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TY - JOUR

T1 - Comparative pharmacology of a new recombinant FSH expressed by a human cell line

AU - Koechling, Wolfgang

AU - Plaksin, Daniel

AU - Croston, Glenn E.

AU - Jeppesen, Janni V.

AU - Macklon, Kirsten T.

AU - Andersen, Claus Yding

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Follicle-stimulating hormone

KW - Follitropin delta

KW - FSH glycosylation

KW - Gonadotropin clearance

KW - Recombinant FSH

U2 - 10.1530/EC-17-0067

DO - 10.1530/EC-17-0067

M3 - Journal article

C2 - 28450423

AN - SCOPUS:85032592144

SN - 2049-3614

VL - 6

SP - 297

EP - 305

JO - Endocrine Connections

JF - Endocrine Connections

IS - 5

ER -

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

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