Sesoko Station, Tropical Biosphere Research Center, University of the Ryukyus, Sesoko 3422, Motobu, Okinawa 905-0227, Japan.
Comp Biochem Physiol C Toxicol Pharmacol. 2010 Jun;152(1):69-74. doi: 10.1016/j.cbpc.2010.02.014. Epub 2010 Mar 1.
We report the first use of exemestane (EM), a steroidal aromatase inhibitor (AI) commercially known as aromasin, in studies of sex differentiation in fish. The effectiveness of EM was examined in two different age groups of the gonochoristic fish, Nile tilapia (Oreochromis niloticus). Untreated control fish (all female) showed normal ovarian differentiation through 120 days after hatching (dah), whereas fish treated with EM at 1000 and 2000 microg/g of feed from 9 dah through 35 dah, the critical period for sex differentiation, exhibited complete testicular differentiation; all stages of spermatogenic germ cells were evident and well developed efferent ducts were present. Fish treated with EM at 1000 microg/g of feed from 70 dah through 100 dah significantly suppressed plasma estradiol-17beta level and increased level of 11-ketotestosterone. Furthermore, untreated control fish showed strong gonadal expression of the steroidogenic enzymes P450 cholesterol-side chain-cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and cytochrome P450 aromatase (P450arom). In contrast, EM-treated fish showed immunopositive reactions against P450scc and 3beta-HSD but not against P450arom in interstitial Leydig cells. These results indicate that treatment of tilapia juveniles with EM during sex differentiation leads to the development of testes, apparently by a complete suppression of aromatase activity.
我们首次报告了他莫昔芬（Exemestane，EM）在鱼类性别分化研究中的应用，它是一种甾体芳香酶抑制剂（Aromatase Inhibitor，AI），商品名为阿那曲唑（Aromasin）。我们在两种不同年龄的雌雄同体鱼类——尼罗罗非鱼（Oreochromis niloticus）中检验了 EM 的效果。未经处理的对照组（均为雌性）在孵化后 120 天（dah）时表现出正常的卵巢分化，而在 9 dah 至 35 dah（性别分化的关键时期）期间，用饲料中 1000 和 2000 μg/g 的 EM 处理的鱼表现出完全的睾丸分化；所有精原细胞的生殖细胞阶段都明显且发育良好，并有成熟的输出管。从 70 dah 至 100 dah 期间，用饲料中 1000 μg/g 的 EM 处理的鱼显著降低了血浆雌二醇-17β水平，增加了 11-酮睾酮水平。此外，未经处理的对照组鱼的类固醇生成酶 P450 胆固醇侧链裂解酶（P450scc）、3β-羟类固醇脱氢酶（3β-HSD）和细胞色素 P450 芳香酶（P450arom）在性腺中表现出强烈的表达。相比之下，用 EM 处理的鱼在间质莱迪希细胞中表现出对 P450scc 和 3β-HSD 的免疫阳性反应，但对 P450arom 没有反应。这些结果表明，在性别分化期间用 EM 处理罗非鱼幼鱼会导致睾丸的发育，显然是通过完全抑制芳香酶活性。
