Single-Chain Bifunctional Vascular Endothelial Growth Factor (VEGF)-Follicle-Stimulating Hormone (FSH)-C-Terminal Peptide (CTP) Is Superior to the Combination Therapy of Recombinant VEGF plus FSH-CTP in Stimulating Angiogenesis during Ovarian Folliculogenesis
| Autor: | Joyce W. Lustbader, Susan Pollak, Yasuhiro Funahashi, Leslie Lobel, J. Klein, Rhonda K. Trousdale, Nikki Feirt |
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| Rok vydání: | 2007 |
| Předmět: |
Vascular Endothelial Growth Factor A
endocrine system medicine.medical_specialty Angiogenesis medicine.drug_class Recombinant Fusion Proteins Drug Evaluation Preclinical Neovascularization Physiologic CHO Cells Biology chemistry.chemical_compound Follicle-stimulating hormone Cricetulus Endocrinology Ovarian Follicle Cricetinae Internal medicine medicine Animals heterocyclic compounds Ovarian follicle Fertility Agents Female Antral follicle Peptide Fragments Recombinant Proteins Rats Vascular endothelial growth factor Drug Combinations Vascular endothelial growth factor A medicine.anatomical_structure Animals Newborn chemistry Female Folliculogenesis Follicle Stimulating Hormone Gonadotropin Infertility Female hormones hormone substitutes and hormone antagonists Half-Life |
| Zdroj: | Endocrinology. 148:1296-1305 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-1127 |
| Popis: | Infertility technologies often employ exogenous gonadotropin therapy to increase antral follicle production. In an effort to enhance ovarian response, several long-acting FSH therapies have been developed including an FSH-C-terminal peptide (CTP), where the FSH subunits are linked by the CTP moiety from human chorionic gonadotropin, which is responsible for the increased half-life of human chorionic gonadotropin. We found that administration of FSH-CTP for ovarian hyperstimulation in rats blunted ovarian follicle vascular development. In women, reduced ovarian vasculature has been associated with lower pregnancy rates. We were interested in determining whether vascular endothelial growth factor (VEGF) therapy could enhance ovarian angiogenesis in FSH-CTP-treated rats. Coadministration of systemic FSH-CTP plus recombinant VEGF was compared with treatment with a novel, single-chain bifunctional VEGF-FSH-CTP (VFC) analog. For VFC, the FSH portion targets the protein to the ovary and stimulates follicle growth, whereas VEGF enhances local vascular development. Both in vitro and in vivo studies confirm the dual FSH and VEGF action of the VFC protein. Evaluation of ovarian follicle development demonstrates that administration of combination therapy using VEGF and FSH-CTP failed to increase follicle vasculature above levels seen with FSH-CTP monotherapy. However, treatment with VFC significantly increased follicle vascular development while concurrently increasing the number of large antral follicles produced. In conclusion, we report the production and characterization of a long-acting, bifunctional VEGF-FSH-CTP protein that is superior to combination therapy for enhancing VEGF activity in the ovary and stimulating follicular angiogenesis in rats. |
| Databáze: | OpenAIRE |
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