INFLUENCE OF PROGESTERONE ON THE ATHEROPR OTECTIVE EFFECT OF ESTROGENIN AN EXPERIMENTAL MODELL

The aim of the present study was to determine the effect of progestero ne on the estrogen action in the process of atherosclerosis. A total o f 48 female New Zealand White rabbits were ovariectomized. The animals received subsequently a 0.5% cholesterol diet for 12 weeks. During th is cholesterol feeding period, 1 mg estradiol/KG b.wt./week (= O), 25 mg progesterone/KG b.wt./week (= P) or combined estradiol/progesterone (= O-P) administration in above dosages was given intramuscularly in corresponding groups (n = 8 each). Two other groups of 8 animals each received also a combined estrogen/progesterone regimen, however, proge sterone was kept at one third (= O-P/3) or one ninth (O-P/9) of the ab ove mentioned dosage, whereas estrogen was kept on 1 mg/KG b.wt. per w eek. A total of 8 ovariectomized animals served as a control group (K) without hormone treatment, The plasma cholesterol and hormone levels were assessed in 4-week-intervals during the experiment. Before excisi on of the vessels, bromodeoxyuridine labeling was performed to determi ne the extent of cellular proliferation in the atherosclerotic lesions , The aortic arch was analyzed immunohistologically and morphometrical ly, An inhibitory effect of estrogen on intimal plaque size was found in comparison to the control group (intimal area: O: 0.7 +/- 0.5 mm(2) vs, K: 3.7 +/- 2.5 mm(2), p < 0.01) whereas progesterone alone did no t show a significant effect on intimal plaque size (intimal area: 4.0 +/- 2.3 mm(2)), In combination with progesterone (high dose), estrogen was not able to reduce intimal atherosclerosis (intimal area: 3.4 +/- 2.4 mm(2)), However the benefical effect of estrogen was not affected by progesterone, when it was reduced to one third (intimal area: 0.8 +/- 0.7 mm(2)) or to the ninth (intimal area: 0.6 +/- 0.4 mm(2)) of th e highest dosage, The number of proliferating cells were reduced in th e estrogen treated group compared with the control group (O: 3.1% +/- 1.8% vs. K: 8.5% +/- 2.6%, p < 0.01) in contrast to the other groups ( P: 7.2% +/- 1.1%; O-P: 7.1% +/- 2.8%; O-P/3: 5.7% +/- 4.3%; O-P/9: 5.1 % +/- 3.9%). In conclusion, progesterone was dose-dependently able to inhibit the benefical effect of estrogen in experimental atheroscleros is, suggesting that progesterone probably exerts a direct ''interactiv e'' inhibitory effect in the arterial vessel wall on the athero-protec tive action of estrogen.