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 17β-estradiol (E₂) in sheep. A preliminary experiment examined the effect of a 4-d fast on the rate of E₂ 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 E₂ clearance by the liver would result in divergence in biliary extraction of E₂ in fed and fasted wethers receiving comparable levels of exogenous E₂. A marked difference in E₂ clearance between fed and fasted wethers was noted in the preliminary study. Relative to ad libitum-fed wethers, a 4-d fast decreased E₂ clearance by 52%. Serum concentrations of SHBG were increased in long-term energy-restricted and fasted ewes, relative to the concentration in maintenance-fed ewes (P = 0.015). Furthermore, a 5-d fast nearly doubled serum steroid-binding capacity in wethers. The E₂ concentration in bile was 2 times greater in fasted than in fed wethers. This fasting-dependent increase in biliary E₂ may be reflective of the increased serum E₂ in fasted animals, because each 1 pg/mL increase in serum E₂ increased bile E₂ by 0.86 ± 0.12 pg/mL, independent of nutrition (P = 0.002). Our results demonstrate that the rate of clearance of E₂ is decreased during nutritional restriction. Additionally, these data indicate that altered SHBG expression, enterohepatic recirculation, or both are involved in the decreased E₂ clearance during dietary restriction.