Gonadal effects on plasma ACE activity in mice


      Angiotensin-converting enzyme (ACE) regulates blood pressure and is an important target in the management of hypertension. Hypertension is a gender biased disease. Plasma ACE activity is significantly higher in male mice (309 U/l) than female mice (237 U/l) and is reduced significantly upon gonadectomy to 224 and 209 U/l, respectively. Although, the gonads influence plasma ACE activity in both male and female mice, the effect is more pronounced in male mice. Plasma ACE is derived from the cleavage of tissue ACE and lung has the highest concentration of tissue ACE. However, lung ACE activity is not gender dimorphic but increases significantly upon gonadectomy in both male and female. ACE mRNA level in the lung is not influenced by gender or gondaectomy. Therefore, the gonads affect plasma ACE activity by influencing cleavage of tissue ACE to plasma ACE and/or decrease stability of plasma ACE in gonadectomized mice is mediated.


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        • Krege J.H.
        • John S.W.
        • Langenbach L.L.
        • Hodgin J.B.
        • Hagaman J.R.
        • Bachman E.S.
        • Jennette J.C.
        • O'Brien D.A.
        • Smithies O.
        Male-female differences in fertility and blood pressure in ACE-deficient mice.
        Nature. 1995; 375: 146-148
        • Esther Jr, C.R.
        • Howard T.E.
        • Marino E.M.
        • Goddard J.M.
        • Capecchi M.R.
        • Bernstein K.E.
        Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.
        Lab. Invest. 1996; 74: 953-965
        • Hagaman J.R.
        • Moyer J.S.
        • Bachman E.S.
        • Sibony M.
        • Magyar P.L.
        • Welch J.E.
        • Smithies O.
        • Krege J.H.
        • O'Brien D.A.
        Angiotensin-converting enzyme and male fertility.
        Proc. Natl. Acad. Sci. USA. 1998; 95: 2552-2557
        • Parmley W.W.
        Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection.
        Am. J. Med. 1998; 105: 275-315
        • Ehlers M.R.
        • Fox E.A.
        • Strydom D.J.
        • Riordan J.F.
        Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme.
        Proc. Natl. Acad. Sci. USA. 1989; 86: 7741-7745
        • Howard T.E.
        • Shai S.Y.
        • Langford K.G.
        • Martin B.M.
        • Bernstein K.E.
        Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene.
        Mol. Cell. Biol. 1990; 10: 4294-4302
        • Beldent V.
        • Michaud A.
        • Wei L.
        • Chauvet M.T.
        • Corvol P.
        Proteolytic release of human angiotensin-converting enzyme. Localization of the cleavage site.
        J. Biol. Chem. 1993; 268: 26428-26434
        • Ehlers M.R.
        • Chen Y.N.
        • Riordan J.F.
        Spontaneous solubilization of membrane-bound human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells.
        Proc. Natl. Acad. Sci. USA. 1991; 88: 1009-1013
        • Sen I.
        • Samanta H.
        • Livingston Wd.
        • Sen G.C.
        Establishment of transfected cell lines producing testicular angiotensin-converting enzyme. Structural relationship between its secreted and cellular forms.
        J. Biol. Chem. 1991; 266: 21985-21990
        • Wei L.
        • Alhenc-Gelas F.
        • Soubrier F.
        • Michaud A.
        • Corvol P.
        • Clauser E.
        Expression and characterization of recombinant human angiotensin I- converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes.
        J. Biol. Chem. 1991; 266: 5540-5546
        • Ramchandran R.
        • Sen G.C.
        • Misono K.
        • Sen I.
        Regulated cleavage-secretion of the membrane-bound angiotensin- converting enzyme.
        J. Biol. Chem. 1994; 269: 2125-2130
        • Ramchandran R.
        • Sen I.
        Cleavage processing of angiotensin-converting enzyme by a membrane- associated metalloprotease.
        Biochemistry. 1995; 34: 12645-12652
        • Lim S.K.
        • Maquat L.E.
        Human beta-glob in mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap-like structure at the 5′ termini.
        EMBO J. 1992; 11: 3271-3278
        • Lim S.K.
        • Kim H.
        • Lim S.K.
        • bin Ah A.
        • Lim Y.K.
        • Wang Y.
        • Chong S.M.
        • Costantini F.
        • Baumman H.
        Increased susceptibility in Hp knockout mice during acute hemolysis.
        Blood. 1998; 92: 1870-1877
        • Selmanoff M.K.
        • Goldman B.D.
        • Ginsburg B.E.
        Serum testosterone, agonistic behavior, and dominance in inbred strains of mice.
        Horm. Behav. 1977; 8: 107-119
        • Machida T.
        • Yonezawa Y.
        • Noumura T.
        Age-associated changes in plasma testosterone levels in male mice and their relation to social dominance or subordinance.
        Horm. Behav. 1981; 15: 238-245
        • Maruniak J.A.
        • Desjardins C.
        • Bronson F.H.
        Dominant-subordinate relationships in castrated male mice bearing testosterone implants.
        Am. J. Physiol. 1977; 233: E495-E499
        • Chen Y.F.
        • Naftilan A.J.
        • Oparil S.
        Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats.
        Hypertension. 1992; 19: 456-463
        • Ellison K.E.
        • Ingelfinger J.R.
        • Pivor M.
        • Dzau V.J.
        Androgen regulation of rat renal angiotensinogen messenger RNA expression.
        J. Clin. Invest. 1989; 83: 1941-1945
        • Schmalbach N.L.
        • Kutscher C.L.
        Testosterone and the sex difference in blood pressure in mice.
        Pharmacol. Biochem. Behav. 1976; 4: 339-341
        • Gallagher P.E.
        • Li P.
        • Lenhart J.R.
        • Chappell M.C.
        • Brosnihan K.B.
        Estrogen regulation of angiotensin-converting enzyme mRNA.
        Hypertension. 1999; 33: 323-328
        • Esther C.R.
        • Marino E.M.
        • Howard T.E.
        • Machaud A.
        • Corvol P.
        • Capecchi M.R.
        • Bernstein K.E.
        The critical role of tissue angiotens in-converting enzyme as revealed by gene targeting in mice.
        J. Clin. Invest. 1997; 99: 2375-2385
        • Ng K.K.
        • Vane J.R.
        Conversion of angiotensin I to angiotensin II.
        Nature. 1967; 216: 762-766