State key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.
Front Endocrinol (Lausanne). 2022 Jun 6;13:910639. doi: 10.3389/fendo.2022.910639. eCollection 2022.
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 is mainly expressed, is also expressed in the interrenal gland in fish. Until now, the roles of 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 -null zebrafish was generated and analyzed by us. The significantly decreased cortisol concentration was observed both in the -deficient males and females at adult stage. The interrenal gland enlargement, increased pituitary () expression, decreased locomotion activity and response to light-stimulated stress were observed in -deficient fish. Intriguingly, the -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 -deficient males and females were observed. The increased concentration of testosterone (T) and estradiol (E2) was observed in -/- females and -/- males, respectively. By examining the ovaries development of -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 -deficiency resulted in diminished cortisol but accumulated P4 and DHP, which may result in the over-activated oocytes in -deficient females.
不同于细胞色素 P450 家族 17,亚家族 A,成员 1(Cyp17a1),它具有参与产生雄激素和雌激素的甾体生成途径的 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,并且是合成皮质醇所必需的。除了在睾丸和卵巢中表达外,在鱼类的肾上腺中也主要表达。到目前为止,在鱼类中的作用,特别是在性特征发育和下丘脑-垂体-肾上腺(HPI)轴中的作用,研究甚少。为了研究 Cyp17a2 在硬骨鱼中的作用,我们生成并分析了 -/- 斑马鱼。在成年期,-/- 雄性和雌性的皮质醇浓度均显著降低。在 -/- 鱼中观察到肾上腺增大,垂体 ()表达降低,运动活性降低以及对光应激的反应降低。有趣的是,-/- 雄性是可育的,并且胸鳍上有正常的繁殖结节,但雌性不育,生殖乳头缺失,性腺指数(GSI)降低。-/- 雄性和雌性的孕激素(P4),17α,20β-二羟基-4-孕烯-3-酮(DHP)和 11-酮睾酮(11-KT)增加。-/- 雌性和 -/- 雄性的睾丸酮(T)和雌二醇(E2)浓度增加。通过检查 3 个月受精后(mpf)-/- 鱼的卵巢发育,我们观察到卵母细胞过度激活。总之,我们的研究结果表明 Cyp17a2 对于皮质醇的产生和生理功能是必不可少的,而 -/- 导致皮质醇减少,但积累了 P4 和 DHP,这可能导致 -/- 雌性的卵母细胞过度激活。