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) (nanograms per g tissue) and compared with renin activity (micromoles angiotensin I per h/g tissue). In control adult mice renin mRNA and renin activity (in parentheses) 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 four tissues was similar to that of renin activity (1:2:100:17, respectively). Although the values in male kidney were one one-hundredth those in SMG, 1000 to 10000 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 less than 0.005), but was decreased to 42% (+/- 29) of normal by propylthiouracil (P less than 0.05). Propylthiouracil caused a small but significant 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 week, whereas T4, testosterone, or propylthiouracil 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. In conclusion, 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.