Huang Chong, Zhao Yanbin, Hu Jianying
MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Toxics. 2024 Sep 27;12(10):701. doi: 10.3390/toxics12100701.
Forskolin (FSK) is a potent adenylate cyclase activator and may display endocrine-disruptive effects via the disruption of steroidogenesis. Here, we tested this hypothesis by use of the in vitro H295R steroidogenesis assay and the in vivo long-term medaka () exposure assay. The results from the H295R assay demonstrated that the transcriptional levels of a series of genes involved in steroidogenesis, including , , , , , and , were remarkably up-regulated. Meanwhile, the productions of estrogens (17β-estradiol (17β-E) and estrone (E)) and progestins (progesterone (PGT) and 17-hydroxyprogesterone (17-HPT)) were significantly increased, and those of androgens (androstenedione (ADD) and testosterone (TTR)) were significantly inhibited. After waterborne exposure of medaka to FSK for 100 days, the gene expressions of , , , , and were significantly enhanced in the gonads of male medaka. 17β-E2 was remarkably induced, although without statistical significance. In addition, the biomarker genes for estrogenicity, including , , , and , were significantly induced in male medaka livers. Pathological damage to their gonads was further identified. Therefore, the results demonstrated that FSK modulates the transcriptions of steroidogenesis genes and alters hormone levels in vitro and in vivo, which is a mark of endocrine disruption in organisms.
福斯高林（FSK）是一种有效的腺苷酸环化酶激活剂，可能通过干扰类固醇生成而表现出内分泌干扰作用。在此，我们通过体外H295R类固醇生成试验和体内长期青鳉暴露试验来验证这一假设。H295R试验结果表明，一系列参与类固醇生成的基因，包括[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]和[此处基因名称缺失]的转录水平显著上调。同时，雌激素（17β-雌二醇（17β-E）和雌酮（E））和孕激素（孕酮（PGT）和17-羟孕酮（17-HPT））的产量显著增加，而雄激素（雄烯二酮（ADD）和睾酮（TTR））的产量则显著受到抑制。在青鳉经水暴露于FSK 100天后，雄性青鳉性腺中[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]和[此处基因名称缺失]的基因表达显著增强。17β-E2显著诱导，尽管无统计学意义。此外，雄性青鳉肝脏中雌激素毒性生物标志物基因，包括[此处基因名称缺失]、[此处基因名称缺失]、[此处基因名称缺失]和[此处基因名称缺失]显著诱导。进一步鉴定了它们性腺的病理损伤。因此，结果表明FSK在体外和体内调节类固醇生成基因的转录并改变激素水平，这是生物体内分泌干扰的标志。
