Identification of two nuclear androgen receptors in kelp bass (Paralabrax clathratus) and their binding affinities for xenobiotics: comparison with Atlantic croaker (Micropogonias undulatus) androgen receptors.
Identification of two nuclear androgen receptors in kelp bass (Paralabrax clathratus) and their binding affinities for xenobiotics: comparison with Atlantic croaker (Micropogonias undulatus) androgen receptors.
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DOI：
10.1095/biolreprod61.4.1152
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发表时间：
1999-10
影响因子：
3.6
通讯作者：
T. Sperry;Peter Thomas
中科院分区：
文献类型：
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作者：
T. Sperry;Peter Thomas
两个不同的核雄激素受体（AR）被确定在脑和卵巢组织的海带鲈鱼，Paralabrax clathratus，命名为kbAR 1和kbAR 2，这对应于两个核AR，我们以前的特点是在大西洋黄鱼，Micropogonias undulatus，命名为acAR 1和acAR 2。对全脑组织核组分的Scatchard分析表明，kbAR 1对睾酮具有单一类别的高亲和力结合位点（T; K（d）为1。8 nM和B（max）为1.0 pmol/g组织），而kbAR 2卵巢组织的胞质组分具有单一类别的双氢睾酮高亲和力结合位点（DHT; K（d）为0.1 nM和B（max）为0.5 pmol/g组织）。竞争研究表明，kbAR 1和kbAR 2都对雄激素具有特异性。然而，kbAR 1仅以高亲和力结合T，而kbAR 2以高亲和力结合DHT、米勃龙、17 α-甲基睾酮、T和11-酮睾酮。此外，我们研究了结合亲和力的二氯二苯基三氯乙烷及其衍生物，几个羟基化多氯联苯（PCB）同系物，PCB的混合物，和杀菌剂乙烯唑啉及其两种代谢产物M1和M2的两个AR在大西洋黄鱼卵巢，睾丸，脑组织和海带鲈鱼卵巢和脑组织。只有4，4 '-PCB-3-OH和2'，5 '-PCB-3-OH表现出大于50%的[（3）H]睾酮从acAR 1或kbAR 1的置换。相比之下，除乙烯氯唑啉外，所有检查的外源性物质均与睾丸和卵巢组织中的acAR 2结合。睾丸组织中M2、2，2 '5'-PCB-4-OH和o，p '-DDD的结合亲和力最高，它们与EC（50）的结合均小于10 μ M。外源性物质与卵巢组织中kbAR 2的结合亲和力与其与卵巢acAR 2的结合亲和力相似。AR 1和AR 2对天然雄激素和合成类固醇以及异生物质具有不同的结合亲和力，这一发现表明雄激素和某些异生物质的活性将取决于靶组织内存在的AR类型。
Two distinct nuclear androgen receptors (ARs) were identified in brain and ovarian tissues of kelp bass, Paralabrax clathratus, termed kbAR1 and kbAR2, which correspond to the two nuclear ARs we have previously characterized in Atlantic croaker, Micropogonias undulatus, termed acAR1 and acAR2. Scatchard analysis of nuclear fractions of whole brain tissue demonstrated that kbAR1 had a single class of high-affinity binding sites for testosterone (T; K(d) of 1. 8 nM and B(max) of 1.0 pmol/g tissue), whereas cytosolic fractions of kbAR2 ovarian tissue had a single class of high-affinity binding sites for dihydrotestosterone (DHT; K(d) of 0.1 nM and B(max) of 0.5 pmol/g tissue). Competition studies showed that both kbAR1 and kbAR2 were specific for androgens. However, kbAR1 bound only T with high affinity, whereas kbAR2 bound DHT, mibolerone, 17alpha-methyl-testosterone, T, and 11-ketotestosterone with high affinity. In addition, we examined the binding affinities of dichlorodiphenyltrichloroethane and its derivatives, several hydroxylated polychlorinated biphenyl (PCB) congeners, PCB mixtures, and the fungicide vinclozolin and its two metabolites M1 and M2 for the two ARs in Atlantic croaker ovarian, testicular, and brain tissues and in kelp bass ovarian and brain tissues. Only 4, 4'-PCB-3-OH and 2',5'-PCB-3-OH demonstrated greater than 50% displacement of [(3)H]testosterone from either acAR1 or kbAR1. In contrast, with the exception of vinclozolin, all of the xenobiotics examined demonstrated binding to acAR2 in testicular and ovarian tissues. The binding affinities were highest in the testicular tissue with M2, 2,2'5'-PCB-4-OH, and o,p'-DDD all binding with EC(50)s less than 10 microM. The binding affinities of xenobiotics to kbAR2 in ovarian tissue were similar to their binding affinities for ovarian acAR2. The finding that AR1 and AR2 possess different binding affinities for natural androgens and synthetic steroids, as well as for xenobiotics, suggests that the activities of androgens and of certain xenobiotics will depend upon the type of AR present within the target tissue.