title: LAPS-FSH: a new and effective long-acting follicle-stimulating hormone analogue for the treatment of infertility.
abstract: Although several long-acting follicle-stimulating hormone (FSH) therapies have been developed to enhance the ovarian response, a disadvantage of FSH therapy is its relatively short half-life, which requires women to receive one to two injections per day for almost 2 weeks. In the present study, we developed a novel FSH analogue by conjugating recombinant human FSH (rhFSH) and the constant region of the human immunoglobulin G4 fragment via non-peptidyl linkers. The efficacy of the FSH analogue was evaluated in vitro by cAMP level assessments, pharmacokinetic studies and a determination of ovarian weight and by comparing these findings with the results from other FSH analogues. In addition, the total number of antral and Graafian follicles was determined after 7 days of treatment with control, 6µgkg(-1) follitropin β, 6, 12 or 42µgkg(-1) corifollitropin α or 3, 6 or 12µgkg(-1) long acting protein/peptide discovery-follicle-stimulating hormone (LAPS-FSH). As a result, the animals treated with 12µgkg(-1) LAPS-FSH produced additional and larger healthy follicles. These data demonstrate that LAPS-FSH promotes growth and inhibits atresia of the ovarian follicle compared with other available drugs, suggesting that our new drug enhances the efficacy and duration of treatment. It is expected that our new FSH analogue will result in a higher chance of pregnancy in patients who are unresponsive to other drugs.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Jung
authors.affiliation: Hanmi Research Center, Hwaseong-si, Gyeonggi-do, 445-813, Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Park
authors.affiliation: Hanmi Research Center, Hwaseong-si, Gyeonggi-do, 445-813, Korea.
authors.forename: YoungHoon
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Hanmi Research Center, Hwaseong-si, Gyeonggi-do, 445-813, Korea.
authors.forename: Yu Yon
authors.initials: YY
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.affiliation: Hanmi Research Center, Hwaseong-si, Gyeonggi-do, 445-813, Korea.
authors.forename: SeChang
authors.initials: S
authors.lastname: Kwon
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005299:Fertility Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D049668:History, 15th Century; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D007246:Infertility / Q000188:drug therapy* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development; D010060:Ovulation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects* / Q000254:growth & development; D014162:Transfection
chemical_list: D005299:Fertility Agents; D043373:Follicle Stimulating Hormone, Human; D007141:Immunoglobulin Fc Fragments; C000598655:LAPS-FSH peptide; D011962:Receptors, FSH; D011993:Recombinant Fusion Proteins; D000242:Cyclic AMP