Extra-renal transcription of the renin genes in multiple tissues of mice and rats.

Abstract

Expression of the mouse renin genes (Ren-) and Ren-2) and of the unique rat renin gene was determined in several extra-renal tissues of mice and rats by primer-directed enzymatic amplification of cDNAs. In addition to the adrenal glands, testis, and ovaries, renin tlnscripts are detected in the liver, whole brain, and hypothalamus and, at lower levels, in spleen, thymus, lung, and prostate. Expression of the rat renin gene correlates with that of the mouse Ren-) gene with the notable exception of the submaxillary gand where renin transcripts are found only in mice. The levels of renin transcripts in the liver of females from both species are higher than in males. In mice, the relative levels of Ren-I and Ren-2 transcripts vary widely in different tissues. These results support the hypothesis of a local renin-angiotensin system in multiple extra-renal sites and imply the existence of complex mechanisms of regulation of the renin gene, previously thought to be expressed in a tissue-specific manner.Renin plays an important role in the control ofblood pressure by cleaving angiotensinogen into angiotensin I. Circulating renin, in its active and inactive pro-renin forms, is produced by the juxtaglomerular cells of the kidney. In mice, the submaxillary gland (SMG) constitutes another major source of renin. The observation of renin activity in several other extra-renal tissues (for review, see ref. 1) has led to the suggestion of extra-renal renin-angiotensin systems. However, activity measurements are sometimes ambiguous due to nonspecific renin-like activities of other proteases and the possible contribution of blood-borne renin in tissue samples (1). The synthesis of renin in extra-renal sites has been supported by the detection of renin mRNA in tissues including the adrenal glands, testis, ovaries, brain, and heart (2-6).However, in the latter studies, renin mRNA levels are often close to the limit of detection by RNA blot analysis. Furthermore, the methods of detection used in studies of extrarenal renin gene expression have not allowed discrimination between transcripts of the two mouse renin genes, Ren-J and Ren-2.Strains of laboratory mice can be divided in two categories on the basis of SMG renin expression: Strains, such as BALB/c or C3H, that produce small amounts of SMG renin possess a single renin gene, designated Ren-), which encodes for the circulating enzyme. Strains, such as DBA/2 or Swiss, which have an additional copy of the renin gene, designated Ren-2, exhibit 100-fold higher SMG renin (7)(8)(9)(10) resulting from the higher SMG transcription-of Ren-2. Renin activity is higher in the SMG of males and transcriptional regulation of Ren-) and Ren-2 by androgens has been demonstrated (11). In contrast to the SMG, Ren-) and Ren-2 are transcribed at the same level in kidney juxtaglomerular cells (12).To elucidate the mechanisms underlying tissue-specific expression of the mouse and rat renin genes and the differential expression of the two mouse genes, several tissues have been examined for the pr...

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

“…[13][14][15] We, therefore, investigated if deletion of Vhl in extrarenal renin cells has an impact on renin and EPO expression as well. In adrenal glands, brain, heart, liver, and lung of Vhl 2/2REN mice, neither renin nor EPO expression was changed.…”

Angiotensin II influences ovarian follicle development in the transgenic (mRen-2)27 and Sprague-Dawley rat

“…The normal Sprague-Dawley (SD) rat possesses the Ren-1 gene which is responsible for the expression of renin in kidney and low levels of renin in extra-renal tissues (Ekker et al 1989). To study the role of extra-renal RASs in the development of hypertension, the transgenic (mRen-2)27 rat was developed by the introduction of the murine Ren-2 gene into the genome of the SD rat (Mullins et al 1990).…”

High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin

“…Although initially it was thought that this generation depends on the de novo synthesis of renin in the heart, it is now well established that such synthesis does not occur either under normal circumstances (13,24,34,35,40,56) or under pathological conditions (14,31,50). Therefore, the heart must sequester renin from the circulation to synthesize ANG II locally.…”