Document Detail


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.
MedLine Citation:
PMID:  17122074     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rhonda K Trousdale; Susan V Pollak; Jeffrey Klein; Leslie Lobel; Yasuhiro Funahashi; Nikki Feirt; Joyce W Lustbader
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-22
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-16     Completed Date:  2007-04-04     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1296-305     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York City, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
CHO Cells
Cricetinae
Cricetulus
Drug Combinations
Drug Evaluation, Preclinical
Female
Fertility Agents, Female / therapeutic use
Follicle Stimulating Hormone / chemistry,  therapeutic use*
Half-Life
Infertility, Female / drug therapy,  pathology
Neovascularization, Physiologic / drug effects*
Ovarian Follicle / blood supply*,  drug effects,  growth & development*,  pathology
Peptide Fragments / therapeutic use
Rats
Recombinant Fusion Proteins / chemical synthesis,  therapeutic use*
Recombinant Proteins / therapeutic use*
Vascular Endothelial Growth Factor A / chemistry,  therapeutic use*
Grant Support
ID/Acronym/Agency:
DK 063224/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Fertility Agents, Female; 0/Peptide Fragments; 0/Recombinant Fusion Proteins; 0/Recombinant Proteins; 0/Vascular Endothelial Growth Factor A; 9002-68-0/Follicle Stimulating Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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