Circulating estradiol suppresses luteinizing hormone pulse frequency during dietary restriction

The influence of dietary restriction on the negative feedback potency of 17-β-estradiol (E₂) was evaluated in both castrated male (wethers) and female sheep (OVX ewes) during the breeding season. In study 1, OVX ewes received maintenance or restricted dietary energy for 7 weeks or maintenance energy for 6 weeks prior to a 5 day fast (n = 12 ewes/feeding group). Estradiol (0.31 μg E₂/50 kg/h) or vehicle (10% EtOH-saline) was continuously infused into half the animals in each dietary treatment for the final 54 h of the study. The dynamic pattern of LH secretion was assessed during the final 6 h of infusion. Estradiol inhibited luteinizing hormone (LH) pulse amplitude independent of nutrition (P = 0.02); fasting increased mean LH, LH peak height, and LH nadir in the absence of E₂ (P = 0.004, P = 0.02, and P = 0.02, respectively); while E₂ inhibited pulse frequency (P = 0.02) and increased peak width (P = 0.04) in restricted ewes. Interestingly, despite uniform E₂ delivery, serum concentrations of E₂ differed with feeding status. Therefore, 12 wethers were infused with 0.31 μg E₂/50 kg/h (6 fed, 6 fasted) and six wethers received 0.19 μg E₂/50 kg/h (fasted) to establish similar serum concentrations of E₂ in fed (0.31 μg/50 kg/h) and fasted (0.19 μg/50 kg/h) wethers. When fed and fasted wethers had uniform serum concentrations of E₂ LH pulse frequency was suppressed (P < 0.05) in fasted relative to fed animals, supporting the postulate that energy restriction enhances the E₂ negative feedback potency. Collectively, these studies demonstrate that nutrition affects E₂ feedback potency and clearance.