Comparative pharmacology of a new recombinant FSH expressed by a human cell line
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Comparative pharmacology of a new recombinant FSH expressed by a human cell line. / Koechling, Wolfgang; Plaksin, Daniel; Croston, Glenn E.; Jeppesen, Janni V.; Macklon, Kirsten T.; Andersen, Claus Yding.
I: Endocrine Connections, Bind 6, Nr. 5, 2017, s. 297-305.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 6
SP - 297
EP - 305
JO - Endocrine Connections
JF - Endocrine Connections
SN - 2049-3614
IS - 5
ER -
ID: 189411594