RENAL MINERALOCORTICOID RECEPTORS AND HIPPOCAMPAL CORTICOSTERONE-BINDING SPECIES HAVE IDENTICAL INTRINSIC STEROID SPECIFICITY
RENAL MINERALOCORTICOID RECEPTORS AND HIPPOCAMPAL CORTICOSTERONE-BINDING SPECIES HAVE IDENTICAL INTRINSIC STEROID SPECIFICITY
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DOI：
10.1073/pnas.80.19.6056
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
FUNDER, JW
中科院分区：
文献类型：
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作者：
KROZOWSKI, ZS;FUNDER, JW
目前有证据表明，海马糖皮质激素受体(GR)有两类：一类是神经胶质细胞中经典的[~3H]地塞米松([~3H]Dex)结合部位，另一类是神经细胞中的[~3H]皮质酮偏好结合部位。在1uM的合成糖皮质激素RU26988(11.beta.，17.beta.-dihydroxy-17.alpha.-propynylandrost-1，4，6-trien-3-one)存在下，从肾上腺切除/卵巢切除的SD大鼠的海马胞浆中排除[~3H]Dex位点的示踪剂，从去肾上腺/去卵巢的SD大鼠海马胞浆中结合[~3H]Dex到位点(Kd为4度。C，0.77倍。10-9M；65fmol/mg蛋白质)，其特异性顺序如下：醛固酮(Aldo)=9α-氟皮质醇(9α-F-皮质醇)=脱氧皮质酮(DOC)=皮质酮；皮质醇。在RU2688存在下，Dex；[~3H]Aldo、[~3H]DOC和[~3H]皮质酮结合显示出相同的特异性。加入1%去肾上腺/去卵巢大鼠血浆(但不加入56度加热的血浆。C 30分钟)将特异度改变为：9αF-皮质醇。Aldo.gtoreq.Mchgt医生。Dex.gtoreq.皮质酮。皮质醇，与转皮质素对DOC、皮质酮和皮质醇的隔离一致，并类似于经典的矿化皮质激素受体(MR)与肾胞浆中[~3H]Aldo的结合(9αF-皮质醇。Aldo.gtoreq.Mchgt医生。皮质酮。皮质醇.gtoreq.Dex)。通过羟基磷灰石吸附将其他肾脏粘合剂与转皮质酮分离，建立了[~3H]Aldo与MR AS结合的内在特异性：Doc.gtoreq。Aldo.gtoreq.9.αF-皮质醇gtoreq。皮质酮；皮质醇。Dex，与海马区的[~3H]皮质酮结合部位平行。显然，海马区[~3H]皮质酮结合部位和肾脏MR可能对类固醇具有相同的内在特异性，但有明显的特异性差异。在生理条件下，自然产生的类固醇的组织特异性隔离的结果可能是一个组织(肾脏)中的盐皮质激素和另一个组织(海马)中的糖皮质激素占据了相同的类固醇结合物种。
There is current evidence for 2 classes of hippocampal glucocorticoid receptors (GR); one classical, [3H]dexamethasone ([3H]Dex)-binding sites in glial cells, and the other [3H]corticosterone-preferring sites in neuronal cells. In the presence of 1 .mu.M of the synthetic glucocorticoid RU26988 (11.beta.,17.beta.-dihydroxy-17.alpha.-propynylandrost-1,4,6-trien-3-one) to exclude tracer from [3H]Dex sites, hippocampal cytosol from adrenalectomized/ovariectomized Sprague-Dawley rats binds [3H]Dex to sites (Kd at 4.degree. C, 0.77 .times. 10-9 M; 65 fmol/mg of protein) with the following order of specificity: aldosterone (Aldo) = 9.alpha.-fluorocortisol (9.alpha.F-cortisol) = deoxycorticosterone (DOC) = corticosterone > cortisol .mchgt. Dex; [3H]Aldo, [3H]DOC and [3H]corticosterone binding show identical specificity in the presence of RU2688. Addition of 1% adrenalectomized/ovariectomized rat plasma (but not plasma heated at 56.degree. C for 30 min) alters the specificity to: 9.alpha.F-cortisol .gtoreq. Aldo .gtoreq. DOC .mchgt. Dex .gtoreq. corticosterone .gtoreq. cortisol, consistent with sequestration of DOC, corticosterone and cortisol by transcortin and similar to classical mineralocorticoid receptor (MR) binding of [3H]Aldo in renal cytosol (9.alpha.F-cortisol .gtoreq. Aldo .gtoreq. DOC .mchgt. corticosterone .gtoreq. cortisol .gtoreq. Dex). Separation of other renal binders from transcortin by hydroxylapatite adsorption established the intrinsic specificity of [3H]Aldo binding to MR as: DOC .gtoreq. Aldo .gtoreq. 9.alpha.F-cortisol .gtoreq. cortiscosterone > cortisol .mchgt. Dex, parallel to that of the [3H]corticosterone-binding sites in hippocampus. Apparently hippocampal [3H]corticosterone-binding sites and renal MR may have identical intrinsic specificity for steroids, with apparent specificity differences the result of tissue-specific sequestration of naturally occurring steroids other than Aldo and an identical steroid-binding species may be occupied under physiological conditions by a mineralocorticoid in one tissue (kidney) and a glucocorticoid in another (hippocampus).