Studies of the Regulation of Mouse Renin Genes by Measurement of Renin Messenger Ribonucleic Acid*

Abstract
The transcriptional activity of renin genes in the mouse kidney and submandibular gland (SMG) was examined by measurement of renin messenger RNA (mRNA) (ng/g tissue) and compared with renin activity (.mu.M angiotensin I per h/g tissue). In control adult mice renin mRNA and renin activity were 1.8 .+-. 0.24 (11 .+-. 1.1) in male kidney, 3.6 .+-. 0.66 (18 .+-. 2.8) in female kidney, 230 .+-. 34 (903 .+-. 59) in male SMG, and 31 .+-. 6 (188 .+-. 47) in female SMG (mean .+-. SE, n = 6). The ratio of renin mRNA among these 4 tissues were similar to that of renin activity (1:2:100:17, respectively). Although the values in male kidney were 1/100 those in SMG, 1000 to 10,000 times more SMG cells are involved per gram of tissue so that, per renin-synthesizing cell, kidney values would be 10 to 100 times SMG values. Expression of renin gene(s) in a renal juxtaglomerular cell may thus be higher than in a SMG granular duct cell. Values in adult male SMG were a consequence of a 40-fold rise at puberty, were decreased to 16% (.+-. 3.8) by castration, but were not significantly influenced by treatment with testosterone, T4, propylthiouracil, sodium depletion, or spironolactone, Renin mRNA in adult female SMG was 18-fold higher than juvenile values, was increased 10-fold (.+-. 1.6) by testosterone (to adult male levels) and 5.5-fold (.+-. 0.81) by T4 (P < 0.005), but was decreased to 42% (.+-. 29) or normal by propylthiouracil (P < 0.05). Propylthiouracil caused a small but signifcant decrease in testosterone-treated female values. In the kidney renin mRNA was increased 3.0-fold (.+-. 0.30) by captopril, 2.3-fold (.+-. 0.23) by a low sodium diet, and 1.7-fold (.+-. 0.13) by spironolactone after 1 wk, whereas T4, testosterone, or propylthiouracil and had little or no effect. Sialoadenectomy increased renin mRNA and renin in male but not in female kidney, suggesting that a SMG factor, possibly renin, may have a role in suppression of renin synthesis in male kidney. Measurement of renin mRNA suggests that testosterone regulates renin gene expression by a direct effect in male mouse SMG, whereas in the female regulation is by thyroid hormone. In the kidney conditions which increase renin content are accompanied by parallel (5-fold higher) increases in renin mRNA, suggesting enhanced expression of renin gene(s) in renal juxtaglomerular cells in chronic low sodium states.