Iron is an essential nutrient for mammalian cells. Most iron absorption occurs in the duodenal epithelial cells and is regulated by hepcidin, which is produced and secreted in the liver. High hepcidin levels can cause iron deficiency anemia due to iron absorption failure. Inside the cell, iron conjugates with a porphyrin ring and is placed with an iron coordinated to heme. One of the heme-binding proteins, known as progesterone receptor membrane component 1 (Pgrmc1), is a non-canonical progesterone receptor associated with diverse molecular gene regulation. Previous studies showed that Pgrmc1 is related to iron homeostasis via hepcidin; however, these mechanisms remain to be elucidated. In the present study, to investigate the role of Pgrmc1 in mammalian iron metabolism, we introduced Pgrmc1 knockout (KO) mice and performed molecular biological analyses using qPCR and western blotting. Pgrmc1 deficiency decreased Hamp mRNA expression and hepcidin protein levels. However, Pgrmc1 deficiency failed to decrease Hamp transcript expression and hepcidin protein levels in siPGRMC1-transfected HepG2 cells and primary Pgrmc1 KO hepatocytes, respectively. PGRMC1 knockdown cells revealed low HAMP mRNA levels upon cyclic AMP (cAMP) activation, suggesting that PGRMC1 promotes HAMP mRNA transcription via cAMP activation. It has been implicated that hepatic Pgrmc1 cannot control hepcidin directly; however, the internal environment caused by the lack of Pgrmc1 may potentially cause low hepcidin levels.

Carcass grade primarily depends on marbling of intramuscular fat, which is associated with the texture and tenderness of beef. Accordingly, various economical molecular tests for high intramuscular fat in beef have been attempted. Especially, Hanwoo (Korean Cattle) intramuscular fat has higher levels of monounsaturated fatty acids than that in the beef of other cattle. Intramuscular fats are associated with levels of lipid metabolic genes in the liver transcriptome. Therefore, hepatic triglyceride synthesis can considerably increase intramuscular fat. To investigate the relationship between hepatic lipogenesis and carcass grade, we analyzed 52 Hanwoo liver samples from domestic farms, and evaluated lipid levels and transcript levels of glucose and lipid metabolism-related genes according to carcass grade. Oil-Red-O staining revealed fatty livers in high carcass grades. Moreover, we found significantly higher levels of mRNA for lipogenesis, glycolysis, and triglyceride synthesis genes in high carcass grade livers. Importantly, progesterone receptor membrane component 1 (Pgrmc1) levels were significantly lower in high carcass grade livers. As Pgrmc1 suppression is correlated with induction of de novo lipogenesis (DNL) and glycolysis genes, it has a diagnostic impact for high carcass grades. These results could be used for genetic improvements in carcass grades of cattle. More importantly, as Pgrmc1 can be detected in blood peripheral nucleated cells, it also has value for rapid blood diagnosis.

Breast cancer is of enormous concern worldwide and linked with age, sex, hormonal factors, and family history. The treatment of early breast cancer includes treating the disease locally with surgery, radiation therapy, or both and treating microscopic systemic disease with either one or a combination of chemotherapy, endocrine therapy, or biologic therapy. Doxorubicin is a well-known anthracycline antibiotic and antineoplastic drug usually administered to breast cancer patients. However, there have been some reports suggesting that doxorubicin causes side effects such as cardiotoxicity. Furthermore, breast cancer patients on doxorubicin treatment are commonly prescribed steroid suppression therapy. In addition, it has been previously reported that lack of estrogen elevates cardiotoxicity. In this study, we evaluated whether the steroid suppression therapy might influence the cardiotoxicity of doxorubicin. We hypothesized that the presence of a steroid hormone, particularly estrogen, is closely related to doxorubicin action. To investigate the effect of estrogen, mice were divided into four groups: control group, doxorubicin-treated group, ovariectomized group, and ovariectomized plus doxorubicin-treated group. We observed upregulation of inflammatory cytokine gene and downregulation of apoptotic genes in the groups treated with doxorubicin, particularly in the ovariectomized plus doxorubicin-treated group. This suggests that administration of doxorubicin under a non-steroid condition can excessively damage the heart. In summary, combination treatment of hormonal and doxorubicin therapy for breast or many different types of cancer patients must be prescribed with requisite precautions.