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Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis

 Daham Kim  ;  Soohyun Lee  ;  Yoon Hee Cho  ;  Min Jeong Kang  ;  Cheol Ryong Ku  ;  Hyunjin Chi  ;  Jungsuk Ahn  ;  Kyungsun Lee  ;  Jaekyu Han  ;  Susan Chi  ;  Moo Young Song  ;  Sang-Hoon Cha  ;  Eun Jig Lee 
 FRONTIERS IN ENDOCRINOLOGY, Vol.14 : 1132172, 2023-02 
Journal Title
Issue Date
Animals ; CHO Cells ; Chorionic Gonadotropin / therapeutic use ; Cricetinae ; Cricetulus ; Follicle Stimulating Hormone* ; Follicle Stimulating Hormone, Human / therapeutic use ; Humans ; Hypogonadism* / drug therapy ; Male ; Rats ; Recombinant Proteins / therapeutic use ; Semen ; Serum Albumin ; Spermatogenesis
FSH ; gonadotrophin replacement therapy ; hypogonadotropic hypogonadism ; infertility ; testis
IntroductionAdministration of follicle-stimulating hormone (FSH) has been recommended to stimulate spermatogenesis in infertile men with hypogonadotropic hypogonadism, whose sperm counts do not respond to human chorionic gonadotropin alone. However, FSH has a short serum half-life requiring frequent administration to maintain its therapeutic efficacy. To improve its pharmacokinetic properties, we developed a unique albumin-binder technology, termed "anti-serum albumin Fab-associated" (SAFA) technology. We tested the feasibility of applying SAFA technology to create long-acting FSH as a therapeutic candidate for patients with hypogonadotropic hypogonadism. MethodsSAFA-FSH was produced using a Chinese hamster ovary expression system. To confirm the biological function, the production of cyclic AMP and phosphorylation of ERK and CREB were measured in TM4-FSHR cells. The effect of gonadotropin-releasing hormone agonists on spermatogenesis in a hypogonadal rat model was investigated. ResultsIn in vitro experiments, SAFA-FSH treatment increased the production of cyclic AMP and increased the phosphorylation of ERK and CREB in a dose-dependent manner. In animal experiments, sperm production was not restored by human chorionic gonadotropin treatment alone, but was restored after additional recombinant FSH treatment thrice per week or once every 5 days. Sperm production was restored even after additional SAFA-FSH treatment at intervals of once every 5 or 10 days. DiscussionLong-acting FSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-FSH in a clinical setting, potentially representing an important advancement in the treatment of patients with hypogonadotropic hypogonadism.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ku, Cheol Ryong(구철룡) ORCID logo https://orcid.org/0000-0001-8693-9630
Kim, Daham(김다함) ORCID logo https://orcid.org/0000-0003-1871-686X
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Cho, Yoon Hee(조윤희)
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