Dietary restriction reduces the rate of estradiol clearance in sheep (Ovis aries).

Three experiments were designed to test the effect of dietary restriction on clearance of 17beta-estradiol (E(2)) in sheep. A preliminary experiment examined the effect of a 4-d fast on the rate of E(2) clearance in wethers. The second experiment tested the hypothesis that either long-term restriction (7 wk) or a 5-d fast would increase steroid-binding capacity of serum by increasing the concentration of sex hormone-binding globulin (SHBG) in the blood of ovariectomized ewes. In Exp. 3, we hypothesized that nutrition-dependent regulation of E(2) clearance by the liver would result in divergence in biliary extraction of E(2) in fed and fasted wethers receiving comparable levels of exogenous E(2). A marked difference in E(2) clearance between fed and fasted wethers was noted in the preliminary study. Relative to ad libitumfed wethers, a 4-d fast decreased E(2) clearance by 52%. Serum concentrations of SHBG were increased in long-term energy-restricted and fasted ewes, relative to the concentration in maintenancefed ewes (P = 0.015). Furthermore, a 5-d fast nearly doubled serum steroid-binding capacity in wethers. The E(2) concentration in bile was 2 times greater in fasted than in fed wethers. This fasting-dependent increase in biliary E(2) may be reflective of the increased serum E(2) in fasted animals, because each 1 pg/mL increase in serum E(2) increased bile E(2) by 0.86 +/- 0.12 pg/mL, independent of nutrition (P = 0.002). Our results demonstrate that the rate of clearance of E(2) is decreased during nutritional restriction. Additionally, these data indicate that altered SHBG expression, enterohepatic recirculation, or both are involved in the decreased E(2) clearance during dietary restriction.