The Novel Angiotensin-Converting Enzyme (ACE) Homolog, ACE2, Is Selectively Expressed by Adult Leydig Cells of the Testis

Abstract

The metallopeptidase angiotensin-converting enzyme (ACE) plays a pivotal role in the cardiovascular system by generating the vasoconstrictor peptide angiotensin II. A homolog of ACE with different substrate specificity, ACE2, has recently been cloned that shows an expression pattern restricted to endothelial cells of the heart and kidney, epithelial cells of the distal tubule of the kidney, and the testis. Although the importance of ACE2 to cardiac function is already evident, its role in the testis remains unknown. In this study, we report the cloning and expression of human testicular ACE2 and confirm that it is identical to the somatic form of the enzyme. ACE2 catalytic activity was present in membrane preparations of whole testes and Leydig cells from adult rats; expression of the protein in Leydig cells was confirmed by Western immunoblot analysis. Using immunohistochemistry, ACE2 expression was confined to the Leydig cells in the rat testis and to Leydig and Sertoli cells in the human testis. Ablation of the Leydig cells in the rat by the specific toxin, ethane dimethane sulfonate, eliminated ACE2-positive cells from the interstitium. Expression of ACE2 in rat Leydig cells was up-regulated during the development of adult-type Leydig cells at puberty and after ethane dimethane sulfonate treatment. Expression of ACE2 activity in the testis was not significantly altered by manipulation of the pituitary-testicular hormonal axis with sc testosterone implants. These data suggest that ACE2 is a constitutive product of adult-type Leydig cells and may participate in the control of testicular function by as yet unknown mechanisms.

Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult Rat

“…The embryonic side of the placenta is strongly labeled, whereas the maternal side is not. No ACE2 expression could be detected by ISH in the liver or the spleen, nor in the testis, although Leydig cells had been shown previously 28 to express ACE2 (Figure 2).…”

Angiotensin-converting enzyme 2 (ACE2) from raccoon dog can serve as an efficient receptor for the spike protein of severe acute respiratory syndrome coronavirus

“…The protein content of the membrane was determined with a BCA Protein Assay kit (Biyotime), using bovine serum albumin as a standard. The activity of the ACE2 assay was determined as described by Douglas et al (2004) using the ACE2-specific quenched fluorescent substrate QFS (7-methoxycoumarin-4-yl)-acetyl-Ala-Pro-Lys(2,4-dinitrophenyl) (Auspep). Assays were performed in black 96-well plates with 50 mM QFS per reaction and incubated at 37 uC for 1 h. Liberated fluorescence (in relative fluorescence units) was measured at 320-420 nm.…”

Angiotensin-Converting Enzyme 2 (ACE2) in Disease Pathogenesis

“…The catalytic domain has one active site (the zinc metallopeptidase domain) and shows 41.8% sequence identity with the amino domain of ACE. 10, 11 Despite the sequence similarity of their catalytic domains, ACE and ACE2 appear to act on different peptide substrates. Whereas ACE cleaves AngI into AngII, 7,8 ACE2 cleaves a single residue from AngII to generate Ang1-7, 11 which has an opposing role to ACE by counterbalancing AT1R-mediated actions.…”

“…10, 11 Whereas ACE cleaves AngI into AngII, 7,8 ACE2 removes a single residue from AngI to yield Ang1-9, 10,11 and cleaves a single residue from AngII to generate Ang1-7 11 ( Figure 1). Several studies support a counter regulatory role for Ang1-7 by opposing many AT1R-mediated actions.…”