Hormone therapy modulates ET(A) mRNA expression in the aorta of ovariectomised New Zealand White rabbits.
OBJECTIVE
To study the effect of 17beta-estradiol (E(2)) or conjugated equine estrogens (CEE) alone and in combination with norethisterone acetate (NETA) or medroxyprogesterone acetate (MPA) on the endothelin-1 (ET-1) system.


METHODS
New Zealand White rabbits were treated with E(2), CEE, E(2) + NETA, CEE + MPA or placebo. The thoracic aorta and the epicardial coronary artery were used for mRNA expression and myograph analyses, respectively.


RESULTS
E(2) and CEE alone significantly reduced ET-1 receptor subtype A (ET(A)) mRNA expression compared with placebo treatment. The E(2)-induced reduction in ET(A) mRNA expression persisted with the co-administration of NETA, but the CEE induced reduction in ET(A) mRNA expression was not maintained with the co-administration of MPA. Treatment with CEE alone significantly increased endotelin-1 converting enzyme (ECE) mRNA expression and CEE combined with MPA reduced prepro-endothelin-1 (ppET-1) mRNA expression when compared with placebo. ET-1 receptor subtype B mRNA expression and ET-1 induced vasocontraction was unaffected by treatment.


CONCLUSIONS
E(2) and CEE treatment exert potentially beneficial vascular effects through regulation of the ET(A) receptor. The effect was maintained with the co-administration of NETA, but not MPA. The differential effects of specific hormone components may explain the variable effects of hormone therapy on the arterial wall.
susanpedersen@dadlnet.dk
Susan Helene
SH
Pedersen
Lars Bo
LB
Nielsen
Nina Gros
NG
Pedersen
Lisbeth
L
Nilas
Bent
B
Ottesen
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D004338:Drug Combinations; D019332:Endothelin-1; D004966:Estrogens, Conjugated (USP); D012333:RNA, Messenger; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone