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首页> 外文期刊>Cell and Tissue Research >Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones.
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Localization of breast cancer resistance protein (Bcrp) in endocrine organs and inhibition of its transport activity by steroid hormones.

机译：乳腺癌抵抗蛋白（Bcrp）在内分泌器官中的定位以及类固醇激素对其转运活性的抑制作用。

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Breast cancer resistance protein (BCRP) is known for its protective function against the toxic effects of exogenous compounds. In addition to this, a role in the transport of endogenous compounds has been described. Since BCRP in the plasma membrane was shown to be regulated by sex steroids, we investigated the presence and possible role of BCRP in steroid hormone-producing organs. Therefore, the presence and localization of Bcrp was investigated in endocrine organs of wild-type mice. Furthermore, the interaction of various steroid hormones with human BCRP activity was studied. Quantitative PCR revealed Bcrp mRNA in the pituitary and adrenal glands, pancreas, ovary, testis and adipose tissue. Immunohistochemistry revealed the presence of Bcrp in the cortex of the adrenal gland and in plasma membranes of adipocytes. In the pituitary gland, pancreas, ovary and testis, Bcrp was mainly located in the capillaries. The interaction between BCRP and 12 steroid hormones was studied using membrane vesicles of HEK293-BCRP cells. Estradiol, testosterone, progesterone and androstenedione inhibited BCRP-mediated uptake of (3)H-estrone sulphate (E(1)S) most potently, with calculated inhibitory constant (Ki) values of 5.0?±?0.2, 36?±?14, 14.7?±?1.3 and 217?±?13?μM, respectively. BCRP function was attenuated non-competitively, which implies an allosteric inhibition of BCRP-mediated E(1)S transport by these steroids. In conclusion, localization of Bcrp in endocrine organs together with the efficient allosteric inhibition of the efflux pump by steroid hormones are suggestive for a role for BCRP in steroid hormone regulation.
机译：乳腺癌抵抗蛋白（BCRP）以其对外源性化合物的毒性作用的保护作用而闻名。除此之外，已经描述了在内源性化合物的运输中的作用。由于显示质膜中的BCRP受性类固醇调节，因此我们调查了BCRP在类固醇激素产生器官中的存在及其可能的作用。因此，研究了Bcrp在野生型小鼠内分泌器官中的存在和定位。此外，研究了各种类固醇激素与人BCRP活性的相互作用。定量PCR显示垂体和肾上腺，胰腺，卵巢，睾丸和脂肪组织中的Bcrp mRNA。免疫组织化学显示肾上腺皮质和脂肪细胞质膜中存在Bcrp。在脑垂体，胰腺，卵巢和睾丸中，Bcrp主要位于毛细血管中。使用HEK293-BCRP细胞的膜囊泡研究了BCRP和12种类固醇激素之间的相互作用。雌二醇，睾丸激素，孕酮和雄烯二酮最有效地抑制BCRP介导的（3）H-雌酮硫酸盐（E（1）S）的摄取，计算得出的抑制常数（Ki）值为5.0？±0.2、36？±14分别为14.7？±？1.3和217？±？13？μM。 BCRP功能被非竞争性削弱，这意味着这些类固醇对BCRP介导的E（1）S转运的变构抑制作用。总之，Bcrp在内分泌器官中的定位以及类固醇激素对外排泵的有效变构抑制作用提示BCRP在类固醇激素调节中的作用。

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