Influence of androgen on translatable renin mRNA in the mouse submandibular gland.

Abstract

SUMMARY In mature outbred Swiss male mice, submandibular gland renin enzyme activity is 4-and 10-fold higher than in glands of prepubescent males and mature females, respectively. Levels of translatable renin mRNA have been studied in mouse submandibular gland during postnatal development and following administration of testosterone. The [ 35 S]methionine-labeled cell-free translation products directed by male glandular mRNA contain a 47 ± 2 kd renin precursor that is not detected in products coded by prepubescent male or female gland mRNA. This cell-free synthesized precursor is detected immunochemically only in the translation products of gland mRNA from males of 33 days or older and from females receiving testosterone administration, a pattern consistent with the measurements of renin enzyme activity. This increase in biologically active renin mRNA is a selective one, since unfractionated male and female mRNAs have similar overall nucleotide sequence complexity corresponding to 1% of mouse single copy DNA. The cDNA transcribed from male gland mRNA reacts 5-and 10-fold faster with the template mRNA than with female or prepubescent male gland mRNA, respectively, which indicates that the male gland contains abundant nucleotide sequences that exist at low concentration in the female or prepubescent male. Selective hybrid arrested translation confirms that the levels of renin mRNA are lower in the glands of prepubescent males than in those of the mature males. These data indicate that the regulation of renin enzymatic activity by androgens is mediated by an increase in the levels of translatable renin mRNA both during postnatal development and after testosterone administration. (Hypertension 6: 605-613, 1984) KEY WORDS • postnatal development hybrid arrested translation cDNA hybridization • saturation hybridization T HE mouse submandibular gland (SMG) contains an enzyme that resembles renal renin (EC3.4.99.19) physically, chemically, and immunologically.' Studies employing DNA recombinants complementary to SMG renin mRNA have demonstrated that extensive structural homology exists between SMG and renal renins 2 and that at least two genetically distinct forms of renin exist in mouse SMG.3 The high levels of SMG renin and of its mRNA 2 " 6 relative to those of the kidney and the sexually dimorphic expression of SMG renin and several

Processing of One-Chain to Two-Chain Renin in the Mouse Submandibular Gland is Influenced by Androgen

“…ANOVA, p < 0.00 1. (20), though levels o f neither growth hormone nor prolactin peak or change at the times when renin production by SMG changes (20 (3,17). The results o f the present study support this concept.…”

“…Renin enzyme levels in SMG increase greatly with onset of puberty in an androgen-dependent manner (3,4,6). The present study suggests that there are also changes in the biosynthetic processing of active renin in the SMG during ontogeny, with a relative increase in 2-chain renin in the mature male animal.…”

“…By deduction, these data suggest that the overall synthesis and storage of renin must be greatly increased in the male mouse SMG during ontogeny. Indeed, this has been shown to be the case (3,4). The changes in the ratio of I-chain renin to 2-chain renin with age have several possible implications.…”

Renin-Angiotensin System

“…In studies using the mouse submaxillary or submandibular gland, which contains an enzyme physiologically, chemically, and immunologically similar to renal renin, it was reported that the intervention of androgens was needed to elevate renin above the basal level [62]. These findings also demonstrated that androgens increase the renin activity by inducing an increase in the level of translatable renin precursor mRNA [49]. Moreover, it was recently reported that, in male CD-1 mice, renin expression in some extrarenal tissues, including the testis, may be stimulated by androgens [26].…”

Role of renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in Sprague-Dawlay rats: Effect of long-term administration of captopril.

“…The regulation of tissue renin and angiotensinogen gene expression for controlling tissue production of these polype- Effects of long-term fibrosis in rats administration of captopril on spontaneous myocardial ptide were studied by a number of investigators in submandibular gland demonstrating that cytoplasmic renin mRNA was accumulated in response to testosterone (Wilson et al 1981;Pratt et al 1981Pratt et al , 1984. Little is known about the regulation of myocardial renin-angiotensin system, but androgen may accumulate cytoplasmic renin mRNA which potentially influence myocardial function.…”