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PubMed1993

Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth.

In the uterus, estrogen causes a rapid increase in microvascular permeability, followed later by growth of the endometrium, including the richly vascular stroma. Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF or VEG/PF) is an angiogenic protein that is not only a specific mitogen for endothelial cells, but also a potent stimulator of microvascular permeability. Because of these properties, it seems likely that VEG/PF might mediate estrogen-induced increases in uterine vascular permeability and blood vessel growth. Therefore, we determined whether the gene for VEG/PF is expressed in the rat uterus and if mRNA abundance is regulated by steroid hormones, using reverse transcription-polymerase chain reaction. The VEG/PF gene is alternatively spliced and gives rise to three transcripts coding for proteins of 188, 164, and 120 amino acids, which, in turn, form the active dimeric factors. Transcripts for VEG/PF mRNAs were detected in the uterus of the rat by reverse transcription-polymerase chain reaction. The mRNAs for the VEG/PF164 and VEG/PF120 subunits were the dominant forms expressed. Treatment with both estradiol (E2) and estriol (E3) rapidly induced an increase in the level of the two smaller transcripts. The increase was detectable as early as 0.5-1 h and peaked at 2 h. Levels of the two smaller transcripts then declined, but remained above control levels for 24 h. The degree of stimulation of VEG/PF mRNA levels was 8-fold at 2 h. VEG/PF188 mRNA levels were higher by 6 h compared to control values. The increase in VEG/PF mRNA levels in response to E2 was not contingent upon de novo protein synthesis, as it was not blocked by cycloheximide. The increase occurred as rapidly as that of the mRNA for Zif268, an estrogen-induced transcription factor. Progesterone also stimulated the expression (at 6 h) of VEG/PF164 and VEG/PF120, but not that of VEG/PF188. We conclude that the VEG/PF gene is expressed in the rat uterus, and that mRNA levels are rapidly enhanced by estrogen. This response suggests that VEG/PF may be involved in the estrogen-induced increase in permeability and proliferation of uterine blood vessels. The identification of VEG/PF as a primary response gene also suggests that VEG/PF expression may be a prerequisite for the subsequent expression or action of other growth factors in the uterus.

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PubMed1980

[An ultrastructural study of capillary permeability of rabbit ovarian follicles during ovulation using carbon tracer (author's transl)].

The observations that perifollicular capillaries of the ovary become engorged with prominent edema in the theca interna and externa around the time of ovulation, suggest a preovulatory increase in permeability of perifollicular capillaries. In previous study, we reported ultrastructural evidences which suggested the increased permeability of perifollicular capillaries just prior to ovulation. In this study, we further examined the perifollicular capillaries of rabbit ovary by using carbon particles as a tracer at various time intervals after the hCG injection for induction of ovulation. Pinocytotic vesicles exhibited no significant changes in size, number and distribution through all preovulatory stages. Carbon particles were not taken into them. Fenestrations were observed at 0,3,4,6 hrs after the hCG injection, most frequently at 4 hrs, but no carbon particles could penetrate them. Intercellular gaps between two adjacent endothelial cells began to be observed at 10 hrs after the hCG injection. Carbon particles passed through these gaps with staying inside the basement membrane (so-called intramural leaking). These observations indicated that the increased permeability of the perifollicular capillaries, just before ovulation, were due to intercellular gaps.

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