Evidence has accumulated suggesting that steroid hormones have a direct effect on the vascular system. Of special interest is the protective effect of estrogens against cardiovascular diseases. One of the aims of the present study was to investigate the messenger RNA (mRNA) expression of the five classic steroid hormone receptors in the great vessels of the rat (aorta, vena cava, and vena portae) to provide a basis to analyze direct steroid effects on vascular tissue. By applying reverse transcription-PCR we compared the expressions of the steroid hormone receptor mRNAs in the respective vessels of male and female rats. Sex differences in the mRNA levels of the mineralocorticoid (MR), estrogen (ER), and progesterone (PR) receptors were found in venous vessels, but not in the aorta. Focussing on the vena cava in the female rat, we investigated whether the ER is active in the vasculature by analyzing regulation of the PR gene. This gene is known to be regulated by estrogens in classic target organs. PR mRNA expression in venous vessels of female rats decreased after ovariectomy. This effect was reversed by chronic sc treatment with estradiol (E2; 1 microgram/animal day). Progester-one (10 mg/animal day, sc) partly inhibited the effect of E2. Besides E2, the partial agonist tamoxifen stimulated PR mRNA expression in ovariectomized rats, whereas the pure antiestrogen ZM 182780 remained inactive in this experiment. Both E2 and tamoxifen caused an autologous down-regulation of ER mRNA. In conclusion, our study demonstrates for the first time that not only the aorta, but also the venous vessels, represented by the vena cava and the portal vein of the rat, are targets for steroid hormones. The ER in vascular tissue is functionally active and mediates direct modulatory effects of estrogens on gene expression in vascular cells.