The difference in submaxillary gland (SMG) renin activity of male and female mice is mediated by androgen. However, because hypophysectomy causes a profound decrease in basal renin activity and a diminished response to treatment with androgen, the endocrine regulation of SMG renin must involve a hormone (s) in addition to androgen. To explore the relationship between SMG renin activity and pituitary hormones, we injected hypophysectomized or intact female mice with dihydrotestosterone (DHT), T4, and bovine GH singly and in combination. T4 and DHT administered together produced renin specific activity levels in hypophysectomized mice identical to those in intact mice treated with DHT or DHT plus T4. GH had little or no effect on SMG renin activity in intact or hypophysectomized mice either alone or in combination with DHT and/or T4. T4 acted independently of androgen, inducing SMG renin in Tfm/Y mice that are resistant to DHT because they lack functional androgen receptors. T4 also acted independently of the renin regulator (Rnr) gene, inducing SMG renin in mice that carry 6 or s alleles at the Rnr locus. Maximum SMG renin activity is determined by Rnr, however, and remained, in C 57 B L /6 J mice (Rnrb/Rnrb) given T4 and/or DHT, 1/100 th that in identically treated SWR/J mice (Rnrs/Rnrs). Mouse SMG renin is localized in secretory granules of the granular convoluted tubule cells. Granular convoluted tubule cells do not mature in untreated mice hypophysectomized at 3 weeks of age, and treatment with both T 4 and DHT is required to restore the SMG duct system to acini ratio and the granule content of hypophysectomized mice to the levels found in identically treated intact mice. These results establish a major role for T4 in the regulation of SMG renin activity in the mouse and demonstrate that the young hypophysectomized mouse is a useful model in which to examine hormonal interaction in the regulation of gene expression.
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