Tissue Distribution of Human AKR1C3 and Rat Homolog in the Adult Genitourinary System
Tissue Distribution of Human AKR1C3 and Rat Homolog in the Adult Genitourinary System
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DOI：
10.1369/jhc.2008.951384
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发表时间：
2008-09-01
影响因子：
3.2
通讯作者：
Lin, Hsueh-Kung
中科院分区：
文献类型：
--
作者：
Azzarello, Joseph;Fung, Kar-Ming;Lin, Hsueh-Kung
人醛酮还原酶（AKR）1C 3（2型3 α-羟基类固醇脱氢酶/5型17 β-羟基类固醇脱氢酶）催化雄激素、雌激素和前列腺素代谢。因此，AKR 1C 3涉及调节激素靶组织中的雄激素受体、雌激素受体和过氧化物酶体增殖物激活受体γ的配体接近。最近关于ARK 1C 3与包括乳腺癌和前列腺癌在内的各种癌症之间的密切关系的报道暗示AKR 1C 3参与癌症的发展或进展。我们先前描述了针对AKR 1C 3的同种型特异性单克隆抗体的表征，其不与相关的>86%序列同一性的人AKR 1C 1、AKR 1C 2或AKR 1C 4、人醛还原酶AKR 1A 1或大鼠3 α-羟基类固醇脱氢酶（AKR 1C 9）交叉反应。在这项研究中，克隆的鼠单克隆抗体提出了对AKR 1C 3的识别大鼠同源物的鉴定和表征。通过IHC研究了人AKR 1C 3及其大鼠同源物在成人泌尿生殖系统（包括肾脏、膀胱、前列腺和睾丸）中的组织分布。在人类和大鼠中，不仅在经典的激素相关组织如前列腺和睾丸中检测到强免疫反应性，而且在非激素相关组织如肾脏和膀胱中也检测到强免疫反应性。这两种酶的分布相当，但不完全相同的两个物种。这些特征保证了AKR 1C 3在激素相关和非激素相关组织中的未来研究以及用于建立动物模型的啮齿动物同系物的鉴定。（J Histochem Cytochem 56：853-861，2008）
Human aldo-keto reductase (AKR) 1C3 (type 2 3 alpha-hydroxysteroid dehydrogenase/type 5 17 beta-hydroxysteroid dehydrogenase) catalyzes androgen, estrogen, and prostaglandin metabolism. AKR1C3 is therefore implicated in regulating ligand access to the androgen receptor, estrogen receptor, and peroxisome proliferator activating receptor gamma in hormone target tissues. Recent reports on close relationships between ARK1C3 and various cancers including breast and prostate cancers implicate the involvement of AKR1C3 in cancer development or progression. We previously described the characterization of an isoform-specific monoclonal antibody against AKR1C3 that does not cross-react with related, >86% sequence identity, human AKR1C1, AKR1C2, or AKR1C4, human aldehyde reductase AKR1A1, or rat 3 alpha-hydroxysteroid dehydrogenase (AKR1C9). In this study, a clone of murine monoclonal antibody raised against AKR1C3 was identified and characterized for its recognition of rat homolog. Tissue distribution of human AKR1C3 and its rat homolog in adult genitourinary systems including kidney, bladder, prostate, and testis was studied by IHC. A strong immunoreactivity was detected not only in classically hormone-associated tissues such as prostate and testis but also in non-hormone-associated tissues such as kidney and bladder in humans and rats. The distribution of these two enzymes was comparable but not identical between the two species. These features warrant future studies of AKR1C3 in both hormone- and non-hormone-associated tissues and identification of the rodent homolog for establishing animal models. (J Histochem Cytochem 56:853-861, 2008)