The thrust of the application is the same as for the original application: to investigate the physiological interactions between microvascular endothelial cells and luteal steroidogenic cells in the development and function of the primate (rhesus monkey) corpus luteum. The overall hypothesis is that luteal cell-microvascular endothelial cell interactions occur via vascular endothelial growth factor (VEGF) and its receptor and that such interactions are critical for the development and function of the corpus luteum. The 4 Specific Aims are the same as before: 1) identify VEGF producing cells and VEGF target cells (with Flt-1/KDR receptors) in the periovulatory follicle and corpus luteum; 2) investigate the actions of VEGF on endothelial cells isolated from the primate corpus luteum; 3) investigate the factors controlling VEGF expression; 4) determine whether paracrine communication between luteal cells and endothelial cells via VEGF-Flt-1/KDR receptors regulates the development and function of the corpus luteum. To do these studies, endothelial cells are isolated using magnetic beads coated with a lectin. VEGF and VEGF receptor or their mRNAs will be analyzed by immunocytochemistry and Western blotting or by RT-PCR and in situ hybridization, respectively. Interactions between luteal cells and endothelial cells in co-culture or in vivo will be analyzed in the presence of antisense oligonucleotides or neutralizing antibodies that disrupt the VEGF-receptor system. Overall, the proposed research may have relevance to an understanding of certain ovarian disorders such as ovarian hyperstimulation syndrome and luteal phase defects where microvasculature growth may be disrupted.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD022408-11
Application #
6125678
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Yoshinaga, Koji
Project Start
1988-09-30
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
11
Fiscal Year
2000
Total Cost
$276,299
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Other Domestic Higher Education
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Stouffer, Richard L; Zelinski-Wooten, Mary B (2004) Overriding follicle selection in controlled ovarian stimulation protocols: quality vs quantity. Reprod Biol Endocrinol 2:32
Martinez-Chequer, J C; Stouffer, R L; Hazzard, T M et al. (2003) Insulin-like growth factors-1 and -2, but not hypoxia, synergize with gonadotropin hormone to promote vascular endothelial growth factor-A secretion by monkey granulosa cells from preovulatory follicles. Biol Reprod 68:1112-8
Stouffer, R L (2003) Progesterone as a mediator of gonadotrophin action in the corpus luteum: beyond steroidogenesis. Hum Reprod Update 9:99-117
Hazzard, Timothy M; Rohan, Richard M; Molskness, Theodore A et al. (2002) Injection of antiangiogenic agents into the macaque preovulatory follicle: disruption of corpus luteum development and function. Endocrine 17:199-206
Stouffer, Richard L (2002) Pre-ovulatory events in the rhesus monkey follicle during ovulation induction. Reprod Biomed Online 4 Suppl 3:1-4
Hazzard, Timothy M; Xu, Fuhua; Stouffer, Richard L (2002) Injection of soluble vascular endothelial growth factor receptor 1 into the preovulatory follicle disrupts ovulation and subsequent luteal function in rhesus monkeys. Biol Reprod 67:1305-12
Stouffer, R L; Martinez-Chequer, J C; Molskness, T A et al. (2001) Regulation and action of angiogenic factors in the primate ovary. Arch Med Res 32:567-75
Hazzard, T M; Christenson, L K; Stouffer, R L (2000) Changes in expression of vascular endothelial growth factor and angiopoietin-1 and -2 in the macaque corpus luteum during the menstrual cycle. Mol Hum Reprod 6:993-8
Hazzard, T M; Molskness, T A; Chaffin, C L et al. (1999) Vascular endothelial growth factor (VEGF) and angiopoietin regulation by gonadotrophin and steroids in macaque granulosa cells during the peri-ovulatory interval. Mol Hum Reprod 5:1115-21
Sanders, S L; Stouffer, R L (1997) Localization of steroidogenic enzymes in macaque luteal tissue during the menstrual cycle and simulated early pregnancy: immunohistochemical evidence supporting the two-cell model for estrogen production in the primate corpus luteum. Biol Reprod 56:1077-87

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