Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility
Background Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to dev...
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Korean Endocrine Society
2025-02-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://e-enm.org/upload/pdf/enm-2024-2090.pdf |
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| author | Daham Kim Yoon Hee Cho Min Jeong Kang So Jeong Lee Soohyun Lee Bo Hyon Yun Hyunjin Chi Jeongsuk An Kyungsun Lee Jaekyu Han Susan Chi Moo Young Song Sang-Hoon Cha Eun Jig Lee |
| author_facet | Daham Kim Yoon Hee Cho Min Jeong Kang So Jeong Lee Soohyun Lee Bo Hyon Yun Hyunjin Chi Jeongsuk An Kyungsun Lee Jaekyu Han Susan Chi Moo Young Song Sang-Hoon Cha Eun Jig Lee |
| author_sort | Daham Kim |
| collection | DOAJ |
| description | Background Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts. |
| format | Article |
| id | doaj-art-3d65275f2fea4bb3b055f48c1d526678 |
| institution | DOAJ |
| issn | 2093-596X 2093-5978 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj-art-3d65275f2fea4bb3b055f48c1d5266782025-08-20T03:07:20ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782025-02-0140114615510.3803/EnM.2024.20902562Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female InfertilityDaham Kim0Yoon Hee Cho1Min Jeong Kang2So Jeong Lee3Soohyun Lee4Bo Hyon Yun5Hyunjin Chi6Jeongsuk An7Kyungsun Lee8Jaekyu Han9Susan Chi10Moo Young Song11Sang-Hoon Cha12Eun Jig Lee13 Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea Department of Tropical Medicine, Yonsei University College of Medicine, Seoul, Korea Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea AprilBio Co. Ltd., Kangwon National University, Chuncheon, Korea Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, KoreaBackground Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.http://e-enm.org/upload/pdf/enm-2024-2090.pdffollicle stimulating hormonefemale infertilityovulationgonadotropins |
| spellingShingle | Daham Kim Yoon Hee Cho Min Jeong Kang So Jeong Lee Soohyun Lee Bo Hyon Yun Hyunjin Chi Jeongsuk An Kyungsun Lee Jaekyu Han Susan Chi Moo Young Song Sang-Hoon Cha Eun Jig Lee Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility Endocrinology and Metabolism follicle stimulating hormone female infertility ovulation gonadotropins |
| title | Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility |
| title_full | Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility |
| title_fullStr | Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility |
| title_full_unstemmed | Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility |
| title_short | Development of a Long-Acting Follicle-Stimulating Hormone Using Serum Albumin Fab-Associated Technology for Female Infertility |
| title_sort | development of a long acting follicle stimulating hormone using serum albumin fab associated technology for female infertility |
| topic | follicle stimulating hormone female infertility ovulation gonadotropins |
| url | http://e-enm.org/upload/pdf/enm-2024-2090.pdf |
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