Milton Emily M, Cartolano Maria C, McDonald M Danielle
Department of Marine Biology and Ecology, University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, 4600 Rickenbacker Causeway, Miami, FL 33149-1098, USA.
Department of Marine Biology and Ecology, University of Miami Rosenstiel School of Marine, Atmospheric, and Earth Science, 4600 Rickenbacker Causeway, Miami, FL 33149-1098, USA.
Aquat Toxicol. 2023 Apr;257:106444. doi: 10.1016/j.aquatox.2023.106444. Epub 2023 Feb 21.
The toxicity of the polycyclic aromatic hydrocarbons (PAHs) in Deepwater Horizon (DWH) oil is well-established, but a knowledge gap exists regarding how this combination of PAHs affects the vertebrate stress axis. We hypothesized that (1) marine vertebrates exposed to DWH PAHs experience stress axis impairment, and co-exposure to an additional chronic stressor may exacerbate these effects, (2) serotonin (5-hydroxytryptamine; 5-HT) may act as a secondary cortisol secretagogue in DWH PAH-exposed fish to compensate for impairment, and (3) the mechanism of stress axis impairment may involve downregulation of cyclic adenosine monophosphate (cAMP; as proxy for melanocortin 2 receptor (MC2R) functionality), total cholesterol, and/or mRNA expression of CYP1A and steroidogenic proteins StAR, P450scc, and 11β-h at the level of the kidney. We found that in vivo plasma cortisol and plasma adrenocorticotropic hormone (ACTH) concentrations in Gulf toadfish exposed to an environmentally relevant DWH PAH concentration (ΣPAH= 4.6 ± 1.6 μg/L) for 7 days were not significantly different from controls, whether fish were chronically stressed or not. However, the rate of cortisol secretion by isolated kidneys after acute stimulation with ACTH was significantly lower in PAH-exposed toadfish compared to clean seawater (SW) controls. 5-HT does not appear to be acting as a secondary cortisol secretagogue, rather, PAH-exposed + stressed toadfish exhibited significantly lower plasma 5-HT concentrations than clean SW + stressed fish as well as a reduced sensitivity to 5-HT at the level of the kidney. There was a tendency for kidney cAMP concentrations to be lower in PAH-exposed fish (p = 0.069); however, mRNA expression of steroidogenic proteins between control and PAH-exposed toadfish were not significantly different and a significant elevation in total cholesterol concentration in PAH-exposed toadfish compared to controls was measured. Future work is needed to establish whether the slower cortisol secretion rate by isolated kidneys of PAH-exposed fish is detrimental, to determine the potential role of other secretagogues in compensating for the impaired kidney interrenal cell function, and to determine whether there is a reduction in MC2R mRNA expression or an impairment in the function of steroidogenic proteins.
深水地平线（DWH）原油中多环芳烃（PAHs）的毒性已得到充分证实，但对于这种多环芳烃组合如何影响脊椎动物应激轴，仍存在知识空白。我们假设：（1）暴露于DWH多环芳烃的海洋脊椎动物会出现应激轴损伤，同时暴露于另一种慢性应激源可能会加剧这些影响；（2）血清素（5-羟色胺；5-HT）可能在暴露于DWH多环芳烃的鱼类中作为继发性皮质醇促分泌素，以补偿损伤；（3）应激轴损伤的机制可能涉及环磷酸腺苷（cAMP；作为黑皮质素2受体（MC2R）功能的替代指标）、总胆固醇以及肾脏水平上CYP1A和类固醇生成蛋白StAR、P450scc和11β-h的mRNA表达下调。我们发现，暴露于与环境相关的DWH多环芳烃浓度（ΣPAH = 4.6±1.6μg/L）7天的海湾蟾鱼，无论是否长期处于应激状态，其体内血浆皮质醇和血浆促肾上腺皮质激素（ACTH）浓度与对照组相比均无显著差异。然而，与清洁海水（SW）对照组相比，用ACTH急性刺激后，暴露于多环芳烃的蟾鱼离体肾脏的皮质醇分泌速率显著降低。5-HT似乎并未作为继发性皮质醇促分泌素发挥作用，相反，暴露于多环芳烃且处于应激状态的蟾鱼血浆5-HT浓度显著低于清洁海水+应激状态的鱼类，并且在肾脏水平上对5-HT的敏感性降低。暴露于多环芳烃的鱼类肾脏cAMP浓度有降低的趋势（p = 0.069）；然而，对照组和暴露于多环芳烃的蟾鱼之间类固醇生成蛋白的mRNA表达无显著差异，且与对照组相比，暴露于多环芳烃的蟾鱼总胆固醇浓度显著升高。未来需要开展工作，以确定暴露于多环芳烃的鱼类离体肾脏皮质醇分泌速率较慢是否有害，确定其他促分泌素在补偿受损肾脏肾上腺细胞功能中的潜在作用，并确定MC2R mRNA表达是否降低或类固醇生成蛋白功能是否受损。
