Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis
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...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1132172/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Daham Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T07:44:06Z |
| format | Article |
| id | doaj.art-1918d305e8e849a9b113920f2ee15e34 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T07:44:06Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-1918d305e8e849a9b113920f2ee15e342023-02-23T11:02:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11321721132172Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesisDaham Kim0Soohyun Lee1Yoon Hee Cho2Min Jeong Kang3Cheol Ryong Ku4Hyunjin Chi5Jungsuk Ahn6Kyungsun Lee7Jaekyu Han8Susan Chi9Moo Young Song10Sang-Hoon Cha11Eun Jig Lee12Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaAprilBio Co., Ltd., Rm 602, Biomedical Science Building, Kangwon National University, Chuncheon, Republic of KoreaDepartment of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of KoreaIntroductionAdministration 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1132172/fullFSHgonadotrophin replacement therapyhypogonadotropic hypogonadisminfertilitytestis |
| spellingShingle | 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 Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis Frontiers in Endocrinology FSH gonadotrophin replacement therapy hypogonadotropic hypogonadism infertility testis |
| title | Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis |
| title_full | Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis |
| title_fullStr | Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis |
| title_full_unstemmed | Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis |
| title_short | Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis |
| title_sort | long acting recombinant human follicle stimulating hormone safa fsh enhances spermatogenesis |
| topic | FSH gonadotrophin replacement therapy hypogonadotropic hypogonadism infertility testis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1132172/full |
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