Investigation of mechanisms involved in regulation of progesterone catabolism using an overfed versus underfed ewe-lamb model
Investigation of mechanisms involved in regulation of progesterone catabolism using an overfed versus underfed ewe-lamb model
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DOI：
10.2527/jas2017.1719
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发表时间：
2017-12-01
影响因子：
3.3
通讯作者：
Sartori, R.
中科院分区：
文献类型：
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作者：
Mattos, F. C. S. Z.;Canavessi, A. M. O.;Sartori, R.
高摄食量引起的孕酮(P4)分解代谢的改变是营养对生殖的一些影响的基础。根据以前的研究，我们假设高饲料摄入量可能会增加P4的分解代谢，这可能是由于肝脏血流增加所致。然而，也可能有相反的作用，因为循环中的胰岛素增加，这已被证明抑制肝脏中涉及P4分解代谢的关键酶的表达。为了测试在1个月和2个月的时间范围内，哪种效应对循环P4的影响最大，我们使用了一个非循环的母羊模型。控制营养平面，评价对循环胰岛素、外源性P4反应的P4分解代谢和肝脏关键酶的稳态信使核糖核酸的影响。使用了四只F-1杜珀×圣伊内斯母羊(5个月龄，体重约25公斤)。14d后，随机分为自由采食组(Ad)和限制采食组(R)，分别饲喂3.8%DM/kg BW和2%DM/kg BW，共8周。在第4周和第8周，绵羊接受阴道内P4植入以评估P4的分解代谢。按照设计，阿德母羊的日采食量比普通母羊高(分别为1.8SE0.03和0.6Kg/母羊；P<；0.001)，体重周增重也更高(平均值为1.7SE0.12比-0.1Kg/EW[SE0.03]；P<；0.001)。在饲喂后-0.5h至7h采集的样本的平均循环胰岛素，Ad母羊是母羊的5倍以上(最小二乘平均值在第4周和第8周时分别为8.2mU/mLSE0.93和1.5mU/mLSE0.16)和2.2mU/mLSE0.18；P<；0.001。虽然两组都接受了相同的P4处理，但在饲喂后-0.5h至7h采集的样本的平均循环P4，Ad母羊显著低于普通母羊(在第4周和第8周时，最小二乘平均值分别为3.2SE0.32和5.5 ng/mLSE0.32；2.8SE0.28 vs.5.2 ng/mLWK8；P<；0.001)，这表明高采食量母羊的P4分解代谢要大得多。令人意外的是，在第4或第8周，尽管胰岛素显著升高，但饮食对肝脏CYP2C、CYP3A、AKR1C或AKR1D的mRNA浓度没有影响。因此，高能量/饲料摄入量主要增加P4分解代谢，没有证据表明由于胰岛素诱导肝脏P4代谢酶的变化而产生抵消作用。
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. Twentyfour F-1 Dorper x Santa Ines 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]; P < 0.001) and greater weekly gain in BW (means of 1.7 [SE 0.12] vs. -0.1 kg/ewe [SE 0.03]; P < 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 mu IU/mL [SE 0.16], respectively, at wk 4 and 12.0 [SE 1.02] vs. 2.2 mu IU/mL [SE 0.18], respectively, at wk 8; P < 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; P < 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 CYP2C, CYP3A, AKR1C, or AKR1D 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.