Abstract
The structurally related somatic and germinal isoforms of angiotensin-converting enzyme (ACE) contain the same catalytic active center and are encoded by the same gene, whose disruption causes renal atrophy, hypotension, and male sterility. The reason for the evolutionary conservation of both isozymes is an enigma, because, in vitro, they have very similar enzymatic properties. Despite the common enzymatic properties, discrete expression of both isoforms is maintained in alternate cell types. We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace -/- male mice restores fertility without curing their other abnormalities (Ramaraj, P., Kessler, S. P., Colmenares, C. & Sen, G. C. (1998) J. Clin. Invest. 102, 371-378). In this report we tested the biological equivalence of somatic ACE and germinal ACE utilizing an in vivo isozymic substitution approach. Here we report that restoration of male fertility was not achieved by the transgenic expression of enzymatically active, somatic ACE in the sperm of Ace -/- mice. Therefore, the requisite physiological functions of the two tissue-specific isozymes of ACE are not interchangeable.
Highlights
The angiotensin-converting enzyme (ACE)1 has long been regarded as a central player in the renin-angiotensin system through its action in converting angiotensin I to the vasopressive peptide
We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace ؊/؊ male mice restores fertility without curing their other abnormalities
The evolutionary conservation of the two isoforms of ACE indicates that both are functionally indispensable (6). Their tissue-specific expression suggests that the specific physiological function of an isoform requires its expression in the correct tissue, a concept that was experimentally supported by our observation that gACE expression in sperm alone is sufficient for maintaining male fertility (24)
Summary
The angiotensin-converting enzyme (ACE)1 has long been regarded as a central player in the renin-angiotensin system through its action in converting angiotensin I to the vasopressive peptide. We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace ؊/؊ male mice restores fertility without curing their other abnormalities We report that restoration of male fertility was not achieved by the transgenic expression of enzymatically active, somatic ACE in the sperm of Ace ؊/؊ mice.
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