Renal ACE2 activity was significantly higher in male compared to female mice (18.1 vs 11.1 RFU/min/µg protein), a difference dependent on 17beta-oestradiol and independent of sex chromosomes.
Does 17β-oestradiol regulate renal ACE2 activity independently of sex chromosomes in mice?
Sex differences in renal ACE2 activity in mice are driven by the suppressive effects of 17β-oestradiol rather than sex chromosome complement.
Absolute Event Rate: 18.1% vs 11.1%
p-value: p=<0.0001
BACKGROUND: Angotensin converting enzyme 2 (ACE2) is a newly discovered monocarboxypeptidase that counteracts the vasoconstrictor effects of angiotensin II (Ang II) by converting Ang II to Ang-(1-7) in the kidney and other tissues. METHODS: ACE2 activity from renal homogenates was investigated by using the fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH, where Mca is (7-methoxycoumarin-4-yl)-acetyl and Dnp is 2,4-dinitrophenyl. RESULTS: We found that ACE2 activity expressed in relative fluorescence units (RFU) in the MF1 mouse is higher in the male (M) compared to the female (F) kidney ACE2 (RFU/min/μg protein): M 18.1 ± 1.0 versus F 11.1 ± 0.39; P < 0.0001; n = 6. Substrate concentration curves revealed that the higher ACE2 activity in the male was due to increased ACE2 enzyme velocity (Vmax) rather than increased substrate affinity (Km). We used the four core genotypes mouse model in which gonadal sex (ovaries versus testes) is separated from the sex chromosome complement enabling comparisons among XX and XY gonadal females and XX and XY gonadal males. Renal ACE2 activity was greater in the male than the female kidney, regardless of the sex chromosome complement ACE2 (RFU/min/μg protein): intact-XX-F, 7.59 ± 0.37; intact-XY-F, 7.43 ± 0.53; intact-XX-M, 12.1 ± 0.62; intact-XY-M, 12.7 ± 1.5; n = 4-6/group; P < 0.0001, F versus M, by two-way ANOVA. Enzyme activity was increased in gonadectomized (GDX) female mice regardless of the sex chromosome complement whereas no effect of gonadectomy was observed in the males ACE2 (RFU/min/μg protein): GDX-XX-F, 12.4 ± 1.2; GDX-XY-F, 11.1 ± 0.76; GDX-XX-M, 13.2 ± 0.97; GDX-XY-M, 11.6 ± 0.81; n = 6/group. 17β-oestradiol (E2) treatment of GDX mice resulted in ACE2 activity that was only 40% of the activity found in the GDX mice, regardless of their being male or female, and was independent of the sex chromosome complement ACE2 (RFU/min/μg protein): GDX+E2-XX-F, 5.56 ± 1.0; GDX+E2-XY-F, 4.60 ± 0.52; GDX+E2-XX-M, 5.35 ± 0.70; GDX+E2-XY-M, 5.12 ± 0.47; n = 6/group. CONCLUSIONS: Our findings suggest sex differences in renal ACE2 activity in intact mice are due, at least in part, to the presence of E2 in the ovarian hormone milieu and not to the testicular milieu or to differences in sex chromosome dosage (2X versus 1X; 0Y versus 1Y). E2 regulation of renal ACE2 has particular implications for women across their life span since this hormone changes radically during puberty, pregnancy and menopause.
Liu et al. (Fri,) conducted a other in Sex differences in renal ACE2 activity. Male sex / 17beta-oestradiol vs. Female sex / Gonadectomy was evaluated on Renal ACE2 activity (RFU/min/µg protein) (p=<0.0001). Renal ACE2 activity was significantly higher in male compared to female mice (18.1 vs 11.1 RFU/min/µg protein), a difference dependent on 17beta-oestradiol and independent of sex chromosomes.