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Acute Temporal Regulation of Vascular Endothelial Growth/Permeability Factor Expression and Endothelial Morphology in the Baboon Endometrium by Ovarian Steroids

Departments of Obstetrics, Gynecology, Reproductive Sciences and Physiology (E.D.A., G.W.A., A.L.N., J.S.B., D.L.S.), Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Physiological Sciences (G.J.P.), Eastern Virginia Medical School, Norfolk, Virginia 23501

Address all correspondence and requests for reprints to: Eugene D. Albrecht, Ph.D., Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Maryland School of Medicine, Bressler Research Laboratories 11-019, 655 West Baltimore Street, Baltimore, Maryland 21201. E-mail: ealbrech{at}umaryland.edu.

We recently showed that endometrial vascular endothelial growth/permeability factor (VEG/PF) mRNA expression was decreased by ovariectomy of baboons and restored by chronic administration of estrogen. However, it remains to be determined whether this effect of estrogen reflects genomic up-regulation of VEG/PF and leads to an increase in microvascular permeability, an early physiological event in angiogenesis. Therefore, we determined the temporal expression of VEG/PF mRNA in glandular epithelial and stromal cells isolated by laser capture microdissection from and width of microvascular paracellular clefts that regulate vessel permeability in the endometrium of ovariectomized baboons after acute estradiol and/or progesterone administration.

Endometrial VEG/PF mRNA levels were increased in five of five animals within 2 h of estradiol administration and remained elevated at 4 and 6 h. The net increase in glandular epithelial (7.31 ± 2.72 attomol/fmol 18S ribosomal rRNA) and stromal (3.13 ± 0.36) cell VEG/PF mRNA levels after estradiol administration was over 8-fold (P < 0.05) and 2.6-fold (P < 0.01) greater, respectively, than after vehicle (0.90 ± 0.30, glands and 1.20 ± 0.33, stroma). In contrast, endometrial VEG/PF mRNA expression was unaltered by progesterone. After estradiol treatment, endometrial paracellular cleft width was increased (P < 0.01) from a mean (±SE) of 71.6 ± 4.6 nm at 0 h to 101.1 ± 6.4 nm at 6 h, whereas vehicle or progesterone had no effect. We suggest that estrogen has a major role in regulating VEG/PF synthesis and early events in angiogenesis in the primate endometrium.

This work was supported by NIH U54-HD-36207 as part of the NICHD Specialized Cooperative Centers Program in Reproduction Research. A.L.N. was supported by a Lalor Foundation Postdoctoral Fellowship.

Abbreviations: CRS, Competitive reference standards; d, deoxy; LCM, laser capture microdissection; log, logarithm, PF, permeability factor; RNase, ribonuclease; rRNA, ribosomal RNA; RT, reverse transcription; VEG, vascular endothelial growth.

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