Nongenomic inhibition of oxytocin binding by progesterone in the ovine uterus
Nongenomic inhibition of oxytocin binding by progesterone in the ovine uterus
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DOI：
10.1095/biolreprod.103.020180
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发表时间：
2004-01-01
影响因子：
3.6
通讯作者：
Stormshak, F
中科院分区：
文献类型：
--
作者：
Dunlap, KA;Stormshak, F
孕激素（P-4）已被报道抑制催产素（OT）结合其受体在分离的小鼠子宫内膜。本研究的目的是1）检查P-4对OT与其在绵羊子宫内膜中的受体的结合的体内和体外作用，以及2）确定子宫内膜质膜是否具有P-4的高亲和力结合位点。在用雌二醇-17 β加载体（玉米油）P-4处理之前，用雌二醇-17 β（2天）和P-4（5天）序列预处理卵巢切除母羊。或P-4 +米非司酮（RU 486）连续3天。与对照组相比，用10 mg P-4/天治疗母羊3天抑制OT结合（P < 0.01），而同时用孕酮拮抗剂RU 486（10 mg/天）治疗则阻断P-4的作用。同样，用P-4（5 ng/ml）孵育子宫内膜质膜抑制OT的结合（P < 0.05），而P-4的这种作用被RU 486（10 ng/ml）阻断。通过放射受体分析，发现子宫内膜质膜含有P-4和孕酮激动剂普洛孕酮的高亲和力结合位点（Kd分别为1.2 × 10（-9）和1.74 × 10（-10）M）。用P-4（5 ng/ml）孵育子宫内膜质膜可显着增加孕激素结合位点的浓度。过量的未标记的R 5020、P-4、RU 486和OT可竞争性抑制标记的普罗美孕酮（R 5020）的结合，但雌二醇-17 β、皮质醇、睾酮和精氨酸加压素不抑制。这些数据表明P-4对OT与绵羊子宫内膜质膜中OT受体的结合具有直接抑制作用。
Progesterone (P-4) has been reported to inhibit oxytocin (OT) binding to its receptor in isolated murine endometrial membranes. The purpose of the present research was to 1) examine the in vivo and in vitro effect of P-4 on the binding of OT to its receptor in the ovine endometrium and 2) determine whether the endometrial plasma membranes have high-affinity binding sites for P-4. Ovariectomized ewes were pretreated with a sequence of estradiol-17beta (2 days) and P-4 (5 days) before being treated with estradiol-17beta plus either vehicle (corn oil), P-4. or P-4 + mifepristone (RU 486) for 3 consecutive days. Treatment of ewes with 10 mg P-4/day for 3 days suppressed binding of OT (P < 0.01) compared with that of controls, whereas concomitant treatment with the progestin antagonist RU 486 (10 mg/day) blocked the effect of P-4. Similarly, incubation of endometrial plasma membranes with P-4 (5 ng/ml) inhibited binding of OT (P < 0.05), whereas this effect of P-4 was blocked by the presence of RU 486 (10 ng/ml). By radioreceptor assay, the endometrial plasma membranes were found to contain a high-affinity binding site for P-4 and the progestin agonist promegestone (K-d 1.2 X 10(-9) and 1.74 X 10(-10)M, respectively). Incubation of endometrial plasma membranes with P-4 (5 ng/ml) significantly increased the concentration of progestin binding sites. Binding of labeled promegestone (R 5020) was competitively inhibited by excess unlabeled R 5020, P-4, RU 486, and OT but not by estradiol-17beta, cortisol, testosterone, and arginine vasopressin. These data suggest a direct suppressive action of P-4 on the binding of OT to OT receptors in the ovine endometrial plasma membrane.