Evidence for two independent effects of oestradiol benzoate on the renin-angiotensin-aldosterone system

Abstract

Abstract. Plasma renin concentrations (PRC), plasma renin substrate concentration (PRS), plasma aldosterone and cortisol concentrations as well as plama renin activity (PRA) were measured in ovariectomized subjects after im administration of 10 mg oestradiol benzoate (EB). The esterified oestrogen exerts two independent effects on the renin-angiotensin-aldosterone system. 1) 48 h after EB administration, PRS was significantly increased. Similar results were obtained for total plasma cortisol, reflecting transcortin concentration. In both cases, the increase was quantitatively related to the basal concentrations. These observations are consistent with the well known oestrogen-induced protein synthesis in the liver. 2) The elevation of PRC preceded that of PRS and was already significant 11 h after EB injection. The early rise in plasma renin activity was essentially caused by the increase in PRC, whereas an influence of the activated substrate synthesis was found later, between the 2nd and the 4th day post injection. The time course of plasma aldosterone concentration correlated well with the increased PRA. The results provide evidence that EB has two different effects on the renin-aldosterone axis: an early one by elevating renin release and a delayed one by increasing renin substrate synthesis. Whereas the second mechanism can clearly be localized in the liver, extrarenal as well as direct renal effects of EB may be responsible for the renin stimulation.

Chronic Estradiol Treatment Decreases Angiotensin II Receptor Density in the Anterior Pituitary Gland and Adrenal Cortex but Not in the Mesenteric Artery

“…This finding is in agreement with Menard and Call [28] who have shown that estradiol treatment in rats produced a rapid increase within 6 h of plasma renin substrate and that following a transient 48-hour increase, plasma renin activity fell slightly below normal levels by day 6 when plasma renin concentrations were reduced by half. Although conflicting results have been published [for review see 33], it can be generally con cluded that in man, estrogens increase circulating All [5] and plasma renin activity [22,23]. These values approach normal levels with chronic treatment as plasma renin con centrations are being suppressed [23, 27, 28.…”

“…30]. Several re ports [23,30] have suggested that in rats chronically treated with estradiol, homeostatic mechanisms are more efficient in compensating for increased plasma renin substrate than in women taking oral contraceptives or estrogens. It must be emphasized however, that discrepent results may be due to the use of pharmacological doses of estrogens in rats compared to much smaller therapeutic doses used in women.…”