Moffatt R J, Zollers W G, Welshons W V, Kieborz K R, Garverick H A, Smith M F
Department of Animal Sciences, University of Missouri, Columbia 65211.
Domest Anim Endocrinol. 1993 Jan;10(1):21-30. doi: 10.1016/0739-7240(93)90005-v.
Norgestomet is the progestational component present in Syncro-Mate-B, which is used to synchronize estrus in cattle. In post-partum cows, luteal phases anticipated to be short following first ovulation are of normal length when cows are pretreated with norgestomet. Because Syncro-Mate-B is used experimentally as a progestogen to affect uterine function, these studies were conducted to investigate how norgestomet acts at the level of the uterus. Receptor binding assays and a sensitive estrogen bioassay in tissue culture were used to address the possibility that some effects of norgestomet might be mediated through interaction of this compound with steroid hormone receptors other than the progesterone receptor (rP). The source of receptors was high-speed cytosol, prepared from bovine uterine endometrium, which was obtained from cyclic cows. Results of single-point and complete competition analyses comparing norgestomet and progesterone indicated that norgestomet competed even more effectively than did progesterone for specific binding of [3H]progesterone to rP. Results of similar studies, which compared the abilities of norgestomet and diethylstilbestrol to compete with [3H]estradiol for binding by uterine endometrial estrogen receptors (rE), provided no evidence for norgestomet competitive binding to rE. In MCF-7 breast cancer cell bioassays, norgestomet showed weak estrogenic activity, but only at concentrations greater than 1 micromolar. Finally, norgestomet did not compete with [3H]triamcinolone acetonide when present in an 100-fold excess, and only competed with [3H]dexamethasone for binding by endometrial glucocorticoid receptors (rG) when present in the micromolar range. We conclude that, at the concentrations used in synchronizing estrus, norgestomet interacts with bovine endometrium as a progestogen and that its biological actions occur through binding of this compound to rP present in target tissues.
诺孕美特是同步发情激素B中的孕激素成分，用于使母牛发情同步化。在产后母牛中，首次排卵后预期黄体期较短，但在用诺孕美特预处理后，黄体期长度正常。由于同步发情激素B被作为一种孕激素用于实验以影响子宫功能，因此开展了这些研究来探究诺孕美特在子宫水平上的作用机制。采用受体结合试验和组织培养中的灵敏雌激素生物测定法来研究诺孕美特的某些作用是否可能通过该化合物与孕激素受体（rP）以外的甾体激素受体相互作用介导。受体来源是从处于发情周期的母牛获得的牛子宫内膜制备的高速胞质溶胶。比较诺孕美特和孕酮的单点及完全竞争分析结果表明，诺孕美特比孕酮更有效地竞争[3H]孕酮与rP的特异性结合。比较诺孕美特和己烯雌酚与[3H]雌二醇竞争子宫子宫内膜雌激素受体（rE）结合能力的类似研究结果，未提供诺孕美特与rE竞争性结合的证据。在MCF-7乳腺癌细胞生物测定中，诺孕美特仅在浓度大于1微摩尔时显示出弱雌激素活性。最后，当诺孕美特过量100倍时，它不与[3H]曲安奈德竞争，仅在微摩尔范围内时才与[3H]地塞米松竞争结合子宫内膜糖皮质激素受体（rG）。我们得出结论，在用于同步发情的浓度下，诺孕美特作为一种孕激素与牛子宫内膜相互作用，其生物学作用通过该化合物与靶组织中存在的rP结合而发生。
