Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Mol Cell Endocrinol. 2014 Jan 25;382(1):131-138. doi: 10.1016/j.mce.2013.09.014. Epub 2013 Sep 25.
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.
3β-羟甾脱氢酶/异构酶（3β-HSD）是所有活性甾体激素生物合成所必需的，如肾上腺、睾丸、卵巢、皮肤和胎盘分泌的激素。3β-HSD 酶在人和啮齿动物中存在多种同工酶。迄今为止，在小鼠中已鉴定出六种不同的同工酶，这些同工酶被推测在不同组织中发挥不同的作用。我们之前曾表明，鼠类 6 型 3β-HSD 同工酶（Hsd3b6）特异性表达于肾上腺中的醛固酮产生球状带细胞中，并且其过表达导致醛固酮合成异常增加，这揭示了该酶在类固醇生成中的关键（或限速）作用。然而，这种酶对肾上腺外甾体激素合成的潜在贡献知之甚少。这种知识的缺乏部分是由于缺乏可用于免疫组织化学的同工酶特异性抗体。在这里，我们报告了针对 Hsd3b6 的特异性抗体的开发和特性，并展示了针对肾上腺、睾丸、卵巢、皮肤和胎盘的免疫组织化学结果。正如预期的那样，在肾上腺中，Hsd3b6 免疫反应主要局限于产生醛固酮的球状带细胞。相比之下，在产生皮质醇的束状带细胞中没有观察到免疫阳性细胞。在性腺中，虽然卵巢对 Hsd3b6 没有任何可检测到的免疫反应性，但睾丸在产生睾酮的间质莱迪希细胞中显示出强烈的免疫反应性。在皮肤中，只有在皮脂腺中才观察到 Hsd3b6 的阳性免疫反应性，这表明该酶在皮脂腺功能中具有特定的作用。此外，在胎盘组织中，Hsd3b6 特异性存在于围绕胚胎腔的巨大滋养层细胞中，这表明该酶在局部孕激素产生中起作用，孕激素的产生对于胚胎的正常植入和/或妊娠的维持是必需的。总之，我们的数据表明 Hsd3b6 定位于多种特定组织和细胞类型中，可能参与了具有不同生理作用的多种组织特异性甾体激素的生物合成。
