García-Macia M, Rubio-Gonzalez A, de Luxán-Delgado B, Potes Y, Rodríguez-González S, de Gonzalo-Calvo D, Boga J A, Coto-Montes A
Department of Morphology and Cellular Biology, Cellular Biology Area, Faculty of Medicine, University of Oviedo, Julián Clavería s/n, 33006, Oviedo, Spain,
Histochem Cell Biol. 2014 May;141(5):519-29. doi: 10.1007/s00418-013-1170-1. Epub 2013 Dec 6.
The Syrian hamster Harderian gland (HG) is an organ that undergoes physiological autophagy in response to oxidative stress induced by porphyrin production. Porphyrin production in the HG has marked sex differences and is closely linked to reproductive function. In the present study, we observed that the estrous cycle and associated estrogen variations may affect oxidative-stress-induced proteolytic processes. In particular, significant changes in autophagic activity were detected during the estrous cycle. Notably, increased activation of macroautophagy as well as chaperone-mediated autophagy in the estrus phase coincided with a minimal antioxidant capability and the highest protein damage levels. By contrast, autophagic machinery was found to be blocked in the diestrus phase, likely due to mammalian target of rapamycin activation, which could be corroborated by the subsequent pS6K activation. Analogous results were observed regarding proteasome activity, which also showed maximal activity in the estrus phase. Interestingly, all these mechanisms were associated with important morphological changes in the HG during the estrous cycle. We observed statistically significant increases in Type II cells, which may be related to extensive autophagy in the estrus phase. Physiologically, this would result in a significant release of porphyrins specifically when females are more receptive. These data support the role of porphyrins as pheromones, as other authors have previously suggested, thus making the HG a scent organ. In addition, these results suggest a porphyrin-based approach to the treatment of porphyria during pregnancy, a condition for which no treatment is currently known.
叙利亚仓鼠的哈德氏腺（HG）是一个在卟啉生成诱导的氧化应激反应中会发生生理性自噬的器官。HG中的卟啉生成存在显著的性别差异，并且与生殖功能密切相关。在本研究中，我们观察到发情周期及相关的雌激素变化可能会影响氧化应激诱导的蛋白水解过程。特别是，在发情周期中检测到自噬活性有显著变化。值得注意的是，发情期巨自噬以及伴侣介导的自噬的激活增加与最低的抗氧化能力和最高的蛋白质损伤水平相一致。相比之下，在动情间期发现自噬机制被阻断，这可能是由于雷帕霉素哺乳动物靶点的激活，随后的pS6K激活可以证实这一点。关于蛋白酶体活性也观察到了类似的结果，其在发情期也显示出最大活性。有趣的是，所有这些机制都与发情周期中HG的重要形态变化有关。我们观察到II型细胞有统计学上的显著增加，这可能与发情期广泛的自噬有关。从生理上讲，这将导致卟啉的大量释放，特别是当雌性更易受孕时。这些数据支持了卟啉作为信息素的作用，正如其他作者之前所建议的，从而使HG成为一个嗅觉器官。此外，这些结果提示了一种基于卟啉的方法来治疗妊娠期卟啉症，目前尚无针对该病症的治疗方法。
