Key result
17beta-estradiol and conjugated equine estrogens significantly reduced ETA mRNA expression compared with placebo, an effect maintained with NETA but not MPA.
Why the study?
Does hormone therapy (estrogens alone or with progestins) modulate the endothelin-1 system in ovariectomised New Zealand White rabbits?
Does hormone therapy (estrogens alone or with progestins) modulate the endothelin-1 system in ovariectomised New Zealand White rabbits?
Estrogen therapy exerts potentially beneficial vascular effects by downregulating ETA receptors, but this effect is differentially modulated by specific progestins.
May indicate progestin-specific vascular effects in animal models; leaves open relevance to clinical postmenopausal hormone therapy.
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.
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Pedersen et al. (2009) studied Ovariectomised. 17beta-estradiol (E2) or conjugated equine estrogens (CEE) alone and in combination with NETA or MPA vs. Placebo was evaluated on ET-1 receptor subtype A (ETA) mRNA expression. 17beta-estradiol and conjugated equine estrogens significantly reduced ETA mRNA expression compared with placebo, an effect maintained with NETA but not MPA.
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