Characterization of the Interrenal Gland and Sexual Traits Development in cyp17a2-Deficient Zebrafish.
Characterization of the Interrenal Gland and Sexual Traits Development in cyp17a2-Deficient Zebrafish.
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DOI：
10.3389/fendo.2022.910639
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发表时间：
2022
影响因子：
5.2
通讯作者：
Zhai, Gang
中科院分区：
文献类型：
--
作者：
Shi, Shengchi;Shu, Tingting;Li, Xi;Lou, Qiyong;Jin, Xia;He, Jiangyan;Yin, Zhan;Zhai, Gang
与细胞色素 P450、家族 17、亚家族 A、成员 1 (Cyp17a1) 不同，细胞色素 P450、家族 17、亚家族 A、成员 1 (Cyp17a1) 同时具有参与产生雄激素和雌激素的类固醇生成途径的 17α-羟化酶和 17,20-裂解酶活性，细胞色素 P450、家族 17、亚家族 A、多肽 2 (Cyp17a2) 仅具有 17α-羟化酶活性，并且已知是皮质醇的合成。 cyp17a1除了主要在睾丸和卵巢中表达外，在鱼类的肾间腺中也有表达。到目前为止，cyp17a2 在鱼类中的作用，特别是在性状发育和下丘脑-垂体-肾间 (HPI) 轴中的作用，研究很少。为了研究 Cyp17a2 在硬骨鱼中的作用，我们生成并分析了 cyp17a2 缺失的斑马鱼。在成年阶段，cyp17a2 缺陷的雄性和雌性中都观察到皮质醇浓度显着降低。在 cyp17a2 缺陷的鱼中观察到肾间腺增大、垂体阿黑皮质素原 a (pomca) 表达增加、运动活动和对光刺激应激的反应降低。有趣的是，缺乏cyp17a2的雄性具有生育能力，并且胸鳍上有正常的繁殖结节，但雌性则不育，生殖乳头缺陷，性腺体指数（GSI）下降。在 cyp17a2 缺陷的男性和女性中观察到黄体酮 (P4)、17α,20β-二羟基-4-孕烯-3-酮 (DHP) 和 11-酮睾酮 (11-KT) 增加。在 cyp17a2-/- 女性和 cyp17a2-/- 男性中分别观察到睾酮 (T) 和雌二醇 (E2) 浓度增加。通过检查 cyp17a2 缺陷鱼在受精后 3 个月 (mpf) 的卵巢发育，我们观察到卵母细胞过度激活。综上所述，我们的研究结果表明，Cyp17a2 对于皮质醇的产生和生理学是不可或缺的，cyp17a2 缺陷导致皮质醇减少，但 P4 和 DHP 积累，这可能导致 cyp17a2 缺陷女性的卵母细胞过度激活。
Unlike the Cytochrome P450, family 17, subfamily A, member 1 (Cyp17a1), which possesses both 17α-hydroxylase and 17,20-lyase activities involved in the steroidogenic pathway that produces androgens and estrogens, Cytochrome P450, family 17, subfamily A, polypeptide 2 (Cyp17a2) possesses only 17α-hydroxylase activity and is known essential for the synthesis of cortisol. Besides with expressed in testes and ovaries, where the cyp17a1 is mainly expressed, cyp17a2 is also expressed in the interrenal gland in fish. Until now, the roles of cyp17a2 in fish, especially in sexual traits development and hypothalamic-pituitary-interrenal (HPI) axis, are poorly studied. To investigate the roles of Cyp17a2 in teleosts, the cyp17a2-null zebrafish was generated and analyzed by us. The significantly decreased cortisol concentration was observed both in the cyp17a2-deficient males and females at adult stage. The interrenal gland enlargement, increased pituitary proopiomelanocortin a (pomca) expression, decreased locomotion activity and response to light-stimulated stress were observed in cyp17a2-deficient fish. Intriguingly, the cyp17a2-deficient males were fertile and with normal breeding tubercles on the pectoral fin, but females were infertile, deficient in genital papilla and with decreased gonadosomatic index (GSI). The increased progesterone (P4), 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 11-ketotestosterone (11-KT) in the cyp17a2-deficient males and females were observed. The increased concentration of testosterone (T) and estradiol (E2) was observed in cyp17a2-/- females and cyp17a2-/- males, respectively. By examining the ovaries development of cyp17a2-deficient fish at 3 months postfertilization (mpf), we observed that the oocytes were over-activated. Taken together, our findings demonstrate that Cyp17a2 is indispensable for production and physiology of cortisol, and cyp17a2-deficiency resulted in diminished cortisol but accumulated P4 and DHP, which may result in the over-activated oocytes in cyp17a2-deficient females.
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影响因子：
2.7
作者：
Nematollahi, M. A.;van Pelt-Heerschap, H.;Komen, J.
通讯作者：
Komen, J.
DOI：
10.1016/j.jsbmb.2016.02.002
发表时间：
2017-01
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
Auchus RJ
通讯作者：
Auchus RJ
影响因子：
4.1
作者：
Bacila, Irina;Cunliffe, Vincent T.;Krone, Nils P.
通讯作者：
Krone, Nils P.
影响因子：
4
作者：
Li, Nan;Oakes, James A.;Krone, Nils P.
通讯作者：
Krone, Nils P.
影响因子：
2.7
作者：
Ruane, N. M.;Goos, H. J. Th.;Komen, J.
通讯作者：
Komen, J.