J Anim Sci. 2017 Dec;95(12):5537-5546. doi: 10.2527/jas2017.1719.
Alterations in progesterone (P4) catabolism due to high feed intake underlie some effects of nutrition on reproduction. Based on previous research, we hypothesized that high feed intake could potentially increase P4 catabolism, likely due to increased liver blood flow. However, there could also be an opposing action due to increased circulating insulin, which has been shown to inhibit hepatic expression of key enzymes involved in P4 catabolism. To test which effect would have the greatest impact on circulating P4 during a 1- and 2 -mo time frame, we used a noncyclic ewe model. The plane of nutrition was controlled, and effects on circulating insulin, P4 catabolism in response to exogenous P4, and steady state mRNA for key hepatic enzymes were evaluated. Twenty-four F Dorper × Santa Inês ewe lambs (5 mo old and approximately 25 kg BW) were used. After 14 d of adaptation, ewes were randomized into 2 groups: ad libitum fed (Ad), with intake of 3.8% DM/kg BW, or restricted feed intake (R), with 2% DM/kg BW, for 8 wk. At wk 4 and 8, ewes received an intravaginal P4 implant to evaluate P4 catabolism. As designed, Ad ewes had greater daily feed intake than R ewes (means of 1.8 [SE 0.03] and 0.6 kg/ewe [SE 0.01]; < 0.001) and greater weekly gain in BW (means of 1.7 [SE 0.12] vs. -0.1 kg/ewe [SE 0.03]; < 0.001). Mean circulating insulin of samples collected from -0.5 to 7 h after the start of feeding was over 5-fold greater in Ad ewes than in R ewes (least squares means of 8.2 [SE 0.93] vs. 1.5 μIU/mL [SE 0.16], respectively, at wk 4 and 12.0 [SE 1.02] vs. 2.2 μIU/mL [SE 0.18], respectively, at wk 8; < 0.001). Although both groups received the same P4 treatment, mean circulating P4 of samples collected from -0.5 to 7 h after feeding was much lower in Ad ewes than in R ewes (least squares means of 3.2 [SE 0.32] vs. 5.5 ng/mL [SE 0.32], respectively, at wk 4 and 2.8 [SE 0.28] vs. 5.2 ng/mL [SE 0.28], respectively, at wk 8; < 0.001) indicating much greater P4 catabolism in ewes with high feed intake. Unexpectedly, there was no effect of diet on hepatic mRNA concentrations for , , , or at wk 4 or 8 in spite of dramatically elevated insulin. Therefore, high energy/feed intake primarily increased P4 catabolism with no evidence for offsetting effects due to insulin-induced changes in hepatic P4 metabolizing enzymes.
由于高采食量导致的孕激素（P4）代谢改变是营养对繁殖影响的部分原因。基于先前的研究，我们假设高采食量可能会增加 P4 代谢，这可能是由于肝血流量增加所致。然而，由于循环胰岛素增加，也可能会产生相反的作用，因为循环胰岛素已被证明会抑制 P4 代谢中关键酶的肝表达。为了测试在 1 至 2 个月的时间内哪种作用对循环 P4 影响最大，我们使用了非循环的绵羊模型。控制营养水平，并评估了循环胰岛素、对外源 P4 的 P4 代谢反应以及关键肝酶的稳态 mRNA。使用了 24 只 F 多赛特 × 圣塔因尼斯母羊（5 月龄，体重约 25 公斤）。适应 14 天后，将母羊随机分为 2 组：自由采食（Ad），采食量为 3.8% DM/kg BW；或限制采食量（R），采食量为 2% DM/kg BW，持续 8 周。在第 4 和 8 周时，母羊接受阴道内 P4 植入物以评估 P4 代谢。如设计的那样，Ad 母羊的每日采食量大于 R 母羊（均值分别为 1.8 [SE 0.03] 和 0.6 公斤/只 [SE 0.01]；< 0.001），每周体重增加也更大（均值分别为 1.7 [SE 0.12] 和 -0.1 公斤/只 [SE 0.03]；< 0.001）。从开始进食后 -0.5 至 7 小时采集的样本中，Ad 母羊的平均循环胰岛素比 R 母羊高 5 倍以上（第 4 周和第 12 周分别为 8.2 [SE 0.93] 和 1.5 μIU/mL [SE 0.16]，第 8 周分别为 12.0 [SE 1.02] 和 2.2 μIU/mL [SE 0.18]；< 0.001）。尽管两组都接受了相同的 P4 处理，但从开始进食后 -0.5 至 7 小时采集的样本中，Ad 母羊的平均循环 P4 比 R 母羊低得多（第 4 周分别为 3.2 [SE 0.32] 和 5.5 ng/mL [SE 0.32]，第 8 周分别为 2.8 [SE 0.28] 和 5.2 ng/mL [SE 0.28]；< 0.001），表明高采食量母羊的 P4 代谢更多。出乎意料的是，尽管胰岛素水平显著升高，但饮食对第 4 周或第 8 周肝 mRNA 浓度的 、 、 或 没有影响。因此，高能量/采食量主要增加 P4 代谢，没有证据表明由于胰岛素诱导的 P4 代谢酶的变化而产生抵消作用。
