Androgen dependence and tissue specificity of renin messenger RNA expression in mice

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Abstract
Testosterone, a steroid hormone which increases blood pressure by hitherto unknown mechanisms, is known to induce renin synthesis in the submandibular gland (SMG) of mice. Since renin as well as all other components of the renin-angiotensin system are present in organs important for cardiovascular control, e.g. the kidney, heart, adrenal gland and brain, it is of interest to study the effect of testosterone on renin gene expression in these organs. Renin messenger (m) RNA concentrations were measured by a solution hybridization assay using a 32P-labeled mouse SMC renin complementary (c) RNA as a radioactive probe (detection limit: 1 pg renin mRNA). Measurements were performed after 2h and after 2, 7, 14 and 21 days of dihydrotestosterone (DHT) treatment in female NMRI mice. Renin mRNA concentration (values are expressed as pg renin mRNA/ (ig total RNA) in the SMC was significantly increased after 7 days (108 ± 22 in controls versus 630 ± 101 in DHT-treated mice), after 14 days (83 ± 15 in controls versus 743 ± 83 in DHT-treated mice) and after 21 days (107 ± 30 in controls versus 579 ± 76 in DHT-treated mice), but did not reach levels found in untreated male NMRI mice (1021 ± 84). In the kidney, a decrease was observed within 21 days, from 43 ± 4 and 40 ± 4 to 29 ± 2 and 22 ± 1.7pg/|ig in controls and DHT-treated groups, respectively. Values in male mice were 22.5 ± 2.5 pg/ug. In the adrenal glands, we found an immediate increase in renin mRNA concentration after 2h (5.8 ± 1.3pg/ug in controls versus 22.1 ± 2.2pg/ug in DHT-treated mice) and after 2 days (9.9 ± 0.9pg/(ig in controls versus 21.2 ± 3.0pg/|ig in DHT-treated mice). In the brain, renin mRNA concentration increased after 21 days from 0.21 ± 0.01 (controls) to 0.37 ± 0.026 pg/ng after DHT treatment. Our measurements provide evidence for a tissue-specific regulation of renin mRNA by DHT in several organs important for blood pressure control. Moreover, the early increase in renin mRNA in the adrenal gland and the late rise in the brain observed after DHT treatment are of interest in view of the possible importance of renin for steroid synthesis and central cardiovascular control.