Renin biosynthesis by human tumoral juxtaglomerular cells. Evidences for a renin precursor.

Abstract

Abstract. Renin biosynthesis was studied in a juxtaglomerular cell tumor. The tumoral tissue had a high renin content (180 Goldblatt Units/g of tissue), was heavily stained by immunofluorescence using human renin antiserum, and exhibited numerous characteristic secretory granules by electron microscopy. In one series of experiments, renin biosynthesis was studied in tissue slices, by following the incorporation of radiolabeled amino acids into specific immunoprecipitable renin. Time course studies showed that renin was first synthesized in a high molecular weight form, 55,000 mol wt, i.e., 10,000 mol wt higher than that of active renin, and was then converted into a 44,000-mol wt form. In a second series of experiments renin tumoral cells were cultured. Small, round, birefringent cells obtained after collagenase digestion produced renin in both primary culture and subculture media. After 5 d most of the renin found in the culture medium was inactive, but could be activated by trypsin treatment. The tumoral tissue exhibited a strong renin immunofluorescence and numerous secretory granules were observed by electron microscopy. In contrast, the renin-producing cells isolated from this tumor and grown in culture showed little renin immunofluorescence and no secretory granule could be observed. The renin-producing cells in primary culture and subculture

Human decidua is a major source of renin.

“…Whether discrepancies between the percent active renin in decidual or endometrial homogenates are real or artifact remains to be determined. Similar findings were reported in a renin-secreting renal tumor (37) in which tumor tissue homogenates contained 72% active renin, while in cultured tumor cells the percent active renin decreased to as low as 3% after 2 wk of culture. Hence, decidua may produce relatively larger quantities of active renin in vivo than when cultured in vitro.…”

Renin, a secretory glycoprotein, acquires phosphomannosyl residues.

“…As shown in Fig. 2 A, renin present inside oocytes (lanes [1][2][3][4][5][6] and in the medium (lanes 7 and 8) bound to the receptor column and was specifically eluted with Man-6-P, indicating the presence of the Man-6-P marker. The total extent of receptor binding of the intracellular renin increased from 35% to 91% between 10 and 40 h of incubation (Table I), consistent with the posttranslational nature of phosphorylation (13).…”

“…Renin functions to catalyze the first step in the activation pathway of angiotensinogen, and thereby plays a pivotal role in the regulation of blood pressure and extracellular fluid volume (21). There is some evidence that the major action of renin may not occur in the serum but in peripheral tissues, where it is taken up from the serum and acts intracellularly to activate angiotensinogen (1). Although several laboratories have studied the biosynthesis of renin (9,11,27), none have determined whether or not this glycoprotein acquires phosphomannosyl residues and, if so, whether these residues have any role in the targeting of renin to its storage granule or in the peripheral uptake of renin from the serum.…”

Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay.

“…Like many polypeptide hormones and zymogens, renin (EC 3.4.99.19) is synthesized in a prepro form (1) which undergoes sequential processing to a prozymogen (prorenin) and then to the active form of the enzyme (2,3). An increasing body of evidence indicates that the inactive form of the enzyme that accounts for 50-90% of the total amount of renin present normally in the circulation (4) is identical to prorenin (5,6).…”