Beneficial Effects of Renin-Angiotensin System Blockers on Testicular Steroidogenesis

Abstract

Only angiotensin-converting enzyme inhibitor reverted the hormonal and testis alterations caused by the high energy density diet. This suggests that enalapril should be the drug of choice for a patient who presents with previous reproductive dysfunction.

Manipulation of a Locally Expressed Renin-Angiotensin System in the Testis: Implications for Steroidogenesis

“…The study by Alves-Pereira et al (page 1878) provides an analysis of testicular RAS and its relationship to androgen synthesis. 2 Their work expands on previous investigations that have associated alterations of the testis specific RAS to testicular dysfunction, hypertension and dyslipidemia. 3 An early study 3 decades ago by Pandey et al demonstrated the presence of renin, angiotensin converting enzyme (ACE)-1, and angiotensin I and II in purified rat Leydig cells.…”

“…Additionally, this study did not examine angiotensin III and IV or the role of ACE2. 2 Enalapril does not inhibit ACE2 and presumably its catalytic function is preserved in this model. As ACE2 is predominately expressed in Leydig cells, its products undoubtedly represent a major driver of cell behavior.…”

“…Given that angiotensin II antiserum cross reacts with other angiotensins, their findings may corroborate the earlier work of Douglas et al 8 This month the report by Alves-Pereira et al expands on the possible RAS driven mechanism for the link between dyslipidemia and hypogonadism. 2 They used a high energy density diet (HED) to induce both hypercholesterolemia and hypertension in a mouse model. Several common RAS inhibitors were administered, including aliskiren (direct renin inhibitor), enalapril (ACE1 inhibitor) and losartan (angiotensin II receptor blocker), in an attempt to alter the HED effects on androgen synthesis.…”

“…2 Their data demonstrate a protective effect with ACE1 blockade, although the exact mechanism remains elusive and generates further questions. Current evidence suggests that ACE1 is not a prominent enzyme in the adult Leydig cell, and angiotensin III and IV, and ACE2 may serve as the regulators of testicular steroidogenesis.…”

This Month in Investigative Urology

“…3 Mice were fed standard chow or a high energy density diet (HED) known to increase blood pressure (BP) and plasma lipids. HED animals were then divided into groups that received HED or HED with the renin inhibitor aliskiren, the angiotensin-converting enzyme (ACE) inhibitor enalapril or the angiotensin type 1 receptor (AT1R) blocker losartan.…”