Martinez Bridget, Scheibner Michael, Soñanez-Organis José G, Jaques John T, Crocker Daniel E, Ortiz Rudy M
Department of Molecular and Cellular Biology, University of California Merced, 5200 North Lake Road, Merced, CA 95343, USA.
Department of Physics, University of California Merced, 5200 North Lake Road, Merced, CA 95343, USA.
Gen Comp Endocrinol. 2017 Oct 1;252:36-47. doi: 10.1016/j.ygcen.2017.07.023. Epub 2017 Jul 22.
Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals.
甲状腺激素（TH）可提高细胞代谢水平。哺乳动物禁食时，甲状腺的反应性通常会降低，这是为了抑制细胞代谢并减轻饥饿感。然而，在长期禁食的海象幼崽中，细胞内由TH介导的蛋白质上调，且TH水平随禁食时间延长而维持稳定。甲状腺在这一明显矛盾现象中的功能及作用尚不清楚，在生理上也令人困惑。在此，我们表明，在长期食物缺乏期间，甲状腺仍保持反应性，并且其在海象体内的功能及TH分泌量随禁食时间延长而增加。我们发现，对外源甲状腺刺激激素作出反应的模拟血浆TH数据可预测细胞信号传导，这一结果得到了酶表达数据的独立验证。数据表明，北海象甲状腺的调节和功能在禁食动物中是非典型的，可更好地描述为“适应性禁食”。此外，模拟数据有助于证实所测得的体内反应，为激素清除、分泌率及甲状腺反应性提供了独特见解。由于这些独特的内分泌反应与几乎完全依赖脂质氧化同时发生，这些发现提供了一个有趣的模型，有助于更好地理解TH介导的对脂质代谢的依赖，而病态肥胖的人类不存在这种情况。结合细胞和组织特异性反应，这些数据提供了对甲状腺状态更综合的评估，可推广应用于许多禁食/食物缺乏的哺乳动物。
