Immunolocalization of murine type VI 3β-hydroxysteroid dehydrogenase in the adrenal gland, testis, skin, and placenta
Immunolocalization of murine type VI 3β-hydroxysteroid dehydrogenase in the adrenal gland, testis, skin, and placenta
复制标题
小鼠 VI 型 3β-羟基类固醇脱氢酶在肾上腺、睾丸、皮肤和胎盘中的免疫定位
DOI：
10.1016/j.mce.2013.09.014
复制
发表时间：
2014
影响因子：
4.1
通讯作者：
Hitoshi Okamura
中科院分区：
文献类型：
--
作者：
Koki Yamamura;Magao Doi;Hida Hayashi;Takumi Ota;Iori Murai;Yunhong Hotta;Rie Komatsu;Hitoshi Okamura
3β-羟基类固醇脱氢酶/异构酶（3β-HSD）是所有活性类固醇激素（如肾上腺、睾丸、卵巢、皮肤和胎盘分泌的类固醇激素）生物合成所必需的酶。3β-HSD酶在人类和啮齿动物中以多种亚型存在。迄今为止，已经在小鼠中鉴定出六种不同的同种型，并且推测这些同种型在不同组织中发挥不同的作用。我们以前发现，小鼠VI型3β-HSD亚型（Hsd 3b 6）在肾上腺内产生醛固酮的肾小球细胞中特异性表达，其过表达导致醛固酮合成异常增加，揭示了这种酶在类固醇生成中的关键（或限速）作用。然而，这种酶对肾上腺外类固醇激素合成的潜在贡献知之甚少。这种知识的缺乏部分是因为缺乏可用于免疫组织化学的同种型特异性抗体。本文报道了Hsd 3b 6特异性抗体的制备和鉴定，以及对肾上腺、睾丸、卵巢、皮肤和胎盘的免疫组化结果。正如预期的那样，Hsd 3b 6免疫反应在肾上腺内基本上局限于肾小球细胞，在那里产生醛固酮。相比之下，在产生皮质酮的束状核中没有观察到免疫阳性细胞。在性腺，而卵巢没有表现出任何可检测到的Hsd 3b 6的免疫反应，睾丸间质Leydig细胞，其中睾酮的产生内表现出强烈的免疫反应。在皮肤中，Hsd 3b 6的阳性免疫反应仅见于皮脂腺，表明这种酶在皮脂腺功能中的特定作用。此外，在胎盘中，Hsd 3b 6特异性地存在于胚胎腔周围的巨大滋养层细胞中，这表明这种酶在适当的胚胎植入和/或维持妊娠所需的局部孕酮产生中的作用。综上所述，我们的数据显示，Hsd 3b 6定位于多种特定的组织和细胞类型，可能因此参与了许多具有不同生理作用的组织特异性类固醇激素的生物合成。
The enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) is essential for the biosynthesis of all active steroid hormones, such as those secreted from the adrenal gland, testis, ovary, skin and placenta. The 3β-HSD enzymes exist in multiple isoforms in humans and rodents. To date, six different isoforms have been identified in the mouse, and these isoforms are speculated to play different roles in different tissues. We previously showed that the murine type VI 3β-HSD isoform (Hsd3b6) is expressed specifically in the aldosterone-producing zona glomerulosa cells within the adrenal gland and that its overexpression causes abnormally increased aldosterone synthesis, revealing a crucial (or rate-limiting) role of this enzyme in steroidogenesis. However, potential contributions of this enzyme to the steroid hormone synthesis outside the adrenal glands are poorly understood. This paucity of knowledge is partly because of the lack of isoform-specific antibody that can be used for immunohistochemistry. Here, we report the development and characterization of specific antibody to Hsd3b6 and show the results of immunohistochemistry for the adrenal gland, testis, ovary, skin and placenta. As expected, Hsd3b6 immunoreactivities within the adrenal gland were essentially confined to the zona glomerulosa cells, where aldosterone is produced. By contrast, no immunopositive cells were observed in the zona fasciculata, which is where corticosterone is produced. In the gonads, while the ovaries did not show any detectable immunoreactivity to Hsd3b6, the testes displayed intense immunoreactivities within the interstitial Leydig cells, where testosterone is produced. In the skin, positive immunoreactivities to Hsd3b6 were only seen in the sebaceous glands, suggesting a specific role of this enzyme in sebaceous function. Moreover, in the placenta, Hsd3b6 was specifically found in the giant trophoblast cells surrounding the embryonic cavity, which suggests a role for this enzyme in local progesterone production that is required for proper embryonic implantation and/or maintenance of pregnancy. Taken together, our data revealed that Hsd3b6 is localized in multiple specific tissues and cell types, perhaps thereby involved in biosynthesis of a number of tissue-specific steroid hormones with different physiological roles.