br Discussion Estradiol is known as one of the
Discussion Estradiol is known as one of the stress signaling molecule [3,4,14]. Here, we showed that PH induced estradiol production before hepatocyte proliferation (Fig. 1). Conversely, the ovariectomized and orchitectomized mice produced less estradiol after PH, and had delayed liver regeneration [3,4]. We conclude that elevated estradiol triggers hepatocyte proliferation after PH. Circulating estradiol concentration is increased in the Estrus thiostrepton receptor (Fig. 4a, and b), after estradiol injection (Fig. 1b–d, Fig. 4c and d), and in late pregnancy (Fig. 2, Fig. 4c). The mRNA expression of ERα is also increased in the late pregnancy and in the hepatocyte located periportal area (Fig. 3). Generally, periportal hepatocytes are active and proliferative, and hepatocyte proliferation starts from the periportal area [3,4]. The elevated estradiol in the Estrus cycle induces ERα expression in the periportal hepatocytes, and proliferation. Milona et al. (2010) reported that pregnancy induces hepatocyte hypertrophy associated with cell-cycle progression without mitosis as they did not observe significant change mitotic figure (%) between non-pregnant and pregnant mice . Here, we showed that more than three-fold differences of mitotic figure (%) were observed in the Estrus cycle (ca 0.08–0.3%; Fig. 4b), which indicate that non-pregnant mice should have all four stages of the Estrus cycle. If they use estrus cycle (just before ovulation) mice as a non-pregnant control, may have a different result of pregnancy-induced hepatocyte proliferation.
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Conflicts of interest
Acknowledgements We are grateful to our department members in the NCGG for their helpful discussions. This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT 18659493), the Japan Science and Technology Agency (A-STEP-AS2312036G and FY2013-SICP) and NCGG (28-25) to T.I.
Introduction In response to sensing infections and injury, the immune system initiates and amplifies expression of innate immunity genes and adaptive immune responses. This burst of inflammatory activity is important in surmounting the infection or repairing the injury, but it is intended to be a local and time-limited event that normally undergoes abatement. When resolution is limited or incomplete, inflammation becomes chronic. Within the central nervous system, this deregulation of inflammation can be linked to neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Within these inflammatory environments, there is typically an overproduction of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), hydroxyl radical (·OH), superoxide (O2–·), and nitric oxide (NO). The role of estrogens and their receptors – estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) – in biology, including inflammation, is complex. Estrogen appears to provide neuroprotection through its actions as a potent anti-oxidant, anti-apoptotic, and anti-inflammatory agent. Therefore, we set out to mask ER ligands for release in the presence of ROS. Boronate esters have been used extensively for the protection or masking of phenols due to their rapid and quantitative release in aqueous H2O2. They have been developed for the selective detection and imaging of H2O2 and since been utilized as pro-drugs of matrix metalloproteinases, masked chelators of metal ions,7, 8 selectively activatable DNA cross-linking agents,9, 10 cytotoxic agents, and pro-drugs of histone deacetylase inhibitors.