J Biomed Transl Res.  2023 Dec;24(4):117-126. 10.12729/jbtr.2023.24.4.117.

Loss of progesterone receptor membrane component 1 decreases hepatic hepcidin levels in animal model

• Mukae M
• Jeong KJ
• Hong EJ

• KMID: 2551409
• DOI: http://doi.org/10.12729/jbtr.2023.24.4.117

Abstract

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.

Keyword

Pgrmc1; hepcidins; iron; cyclic AMP; HAMP