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(540) EFFECT OF ESTROGEN AND PROGESTERONE ON VASCULAR ENDOTHELIAL GROWTH/PERMEABILITY FACTOR EXPRESSION BY GLANDULAR EPITHELIAL AND STROMAL CELLS IN THE BABOON ENDOMETRIUM. Niklaus, Andrea1, Aberdeen, Graham1, Babischkin, Jeffery1, Pepe, Gerald2, Albrecht, Eugene1, 1 Departments of Obstetrics, Gynecology, Reproductive Sciences and Physiology, Baltimore, MD2 Department of Physiological Sciences, Norfolk, VA ABSTRACT- This study determined whether estrogen (E2) and/or progesterone (P4) have a role in vivo in regulating vascular endothelial growth/permeability factor (VEG/PF) expression by particular cells within the primate endometrium. VEG/PF mRNA levels were determined by competitive reverse transcription-polymerase chain reaction (RT-PCR) in glandular epithelial (GE) and stromal (S) cells isolated by laser capture microdissection and VEG/PF protein was determined by immunocytochemistry in the uterus of baboons: during the normal menstrual cycle (n=12) and after ovariectomy (OvX) and administration of E2 and/or P4 in levels designed to replicate the proliferative and secretory phases of the menstrual cycle (same 3 baboons studied longitudinally). Mean (± SE) VEG/PF mRNA levels (attomoles/femtomole 18S rRNA) during the combined E2 surge and secretory phases of the menstrual cycle in GE (2.31 ± 0.82) and S (2.02 ± 0.45) were decreased by 80-90% (P<0.05) after OvX (0.52 ± 0.20 and 0.22 ± 0.11, respectively), which suppressed serum E2 and P4 to nondetectable levels. E2 administration to OvX baboons (serum E2 = 248 ± 54 pg/ml) increased (P<0.05) VEG/PF mRNA to levels in the GE (5.57 ± 1.53) and S (2.61 ± 1.57) which were similar to those in intact baboons. Concomitant administration of E2 and P4 (serum E2 = 64 ± 20 pg/ml, serum P4 = 7.0 ± 2.4 ng/ml) resulted in GE (3.65 ± 1.42) and S (1.25 ± 0.77) VEG/PF mRNA levels which appeared slightly lower than with E2, while P4 alone was less effective on VEG/PF mRNA in GE (2.28 ± 0.74) and S (0.76 ± 0.10). After OvX, VEG/PF protein was expressed in very low levels throughout the endometrium and this was reversed by E2. In summary, E2 was the principal ovarian steroid hormone that regulated endometrial VEG/PF synthesis in the primate, while P4 had a limited effect. Consequently, we propose that estrogen, by sustaining VEG/PF expression by GE and/or S cells, promotes endometrial angiogenesis during the menstrual cycle. Supported by NIH U54 HD-36207 as part of the NICHD Specialized Cooperative Centers Program in Reproduction Research and by a Lalor Foundation Fellowship. KEY WORDS: endometrium, angiogenesis, estrogen, primate |
