Ovarian hormones modulate endothelin A and B receptor expression

Abstract

Aims: The study aims to determine the modulatory roles of ovarian hormones, estrogen (E2) and progesterone (P), on the expression of endothelin A (ETA) and B (ETB) receptors in lung, liver and kidney tissues.

Main methods: Female Sprague-Dawley rats were subjected to bilateral ovariectomy and divided into four groups ovariectomized (OVX), OVX+E2, OVX+P, and OVX+E2+P. A separate group of rats underwent sham surgery and served as a control. Three weeks after OVX or sham surgery, tissues from lungs, liver, renal cortex, and inner medulla were collected, snap-frozen, and kept at -80°C for assessment of ETA and ETB receptor expression using real-time PCR.

Key findings: E2-treated OVX animals had significantly lower expression of ETA receptors in the lungs, compared to OVX rats. Pulmonary ETB receptor mRNA was not measurably affected by any of the interventions. Hepatic ETA and ETB were significantly increased in OVX+E2+P rats, compared to sham rats. Renal inner medullary ETA and ETB receptor expressions were significantly elevated in OVX compared to sham, an effect that was prevented by co-supplementation of OVX with E2 and P. Additionally, both ETA and ETB receptor expression in the renal cortex were significantly attenuated by ovariectomy, and this reduction was not evident in OVX+E2 rats.

Significance: These data suggest that ovarian hormones regulate ET receptor expression and may contribute to sex differences in cardiovascular and renal health.

Keywords: ET(A) receptors; ET(B) receptors; Endothelin; Estrogen; Progesterone.

Fig. 1.

Relative mRNA expression of ET_A (A) and ET_B (B) receptors in lung tissues obtained from sham, ovariectomized (OVX) rats implanted with subcutaneous pellets containing estrogen (OVX + E₂), progesterone (OVX + P), their combination (OVX + E₂ + P) or placebo pellets (OVX). Values represent fold change from sham levels. Data are means ± SE of 4–6 samples in each group. *P < 0.05 vs. sham. ^†P 0.05 vs. OVX.

Fig. 2.

Relative mRNA expression of ET_A (A) and ET_B (B) receptors in liver tissues obtained from sham, ovariectomized (OVX) rats implanted with subcutaneous pellets containing estrogen (OVX + E₂), progesterone (OVX + P), their combination (OVX + E₂ + P) or placebo pellets (OVX). Values represent fold change from sham levels. Data are means ± SE of 5–7 samples in each group. *P < 0.05 vs. sham.

Fig. 3.

Relative mRNA expression of ET_A and ET_B receptors in renal cortex (A & B) and inner medulla (C & D) obtained from sham, ovariectomized (OVX) rats implanted with subcutaneous pellets containing estrogen (OVX + E₂), progesterone (OVX + P), their combination (OVX + E₂ + P) or placebo pellets (OVX). Values represent fold change from sham levels. Data are means ± SE of 4–7 samples in each group. *P < 0.05 vs. sham. ^†P 0.05 vs. OVX.