Comparative effects of estrogen and antiestrogen on plasma renin substrate levels and hepatic estrogen receptors in the rat.

Abstract

Studies were undertaken to compare the effects of the estrogen ethinyl estradiol [llα-ethinylestradiol-17β (EE2)] and the antiestrogen U11.100A [l-(2-[p-(3,4-dihydro-6-methoxy- 2 - phenyl -1 - naphthyl) phenoxy] ethyl) pyrrolidine hydrochloride (UA)] on rat liver. These compounds were assessed for their abilities to bind to estrogen-specific binding sites in liver cytosol, to translocate these sites to the nucleus, and to induce elevations of hepatic production of plasma renin substrate. Both compounds were shown to cause significant 2- to 4-fold increases in plasma renin substrate levels after sc injections at dosages of 25, 100, and 250 μg daily for 2 days to mature female rats, and two related triarylethylene antiestrogens, tamoxifen [trans-l-(4β-dimethylaminoethoxyphenyl) l,2-diphenylbut-l-ene] and CI628 [α-(p-(2-(l-pyrrolidino)ethoxy)phenyl)4-methoxy-α′-nitrostilbene], were equally potent stimulators of elevated plasma renin substrate leve s. Similar approximately 3-fold increases in plasma renin sub...