Hormone therapy modulates ET_A mRNA expression in the aorta of ovariectomised New Zealand White rabbits

Abstract

Objective. To study the effect of 17β-estradiol (E₂) 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 E₂, CEE, E₂ + NETA, CEE + MPA or placebo. The thoracic aorta and the epicardial coronary artery were used for mRNA expression and myograph analyses, respectively.

Results. E₂ and CEE alone significantly reduced ET-1 receptor subtype A (ET_A) mRNA expression compared with placebo treatment. The E₂-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. E₂ 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.

Keywords:

• Hormone therapy
• progestins
• endothelin-1
• gene expression
• New Zealand White rabbit