Dimorphic frataxin and its gene regulation by sex steroids in hamsters

Abstract

The role of frataxin (FXN) has been studied extensively in Friedreich ataxia patients, however, the molecular bases underlining the sex steroid-dependent gene expression profiles of FXN in adult tissues are unknown. I describe the molecular characterization of hamster FXN by examining the sexually dimorphic expression and its regulation by sex steroids. Sequence analysis of FXN cDNA showed 630bp-long ORF encoding 209 amino acids. qPCR analysis revealed that FXN is detected in a wide range of tissues, with the highest expression in the heart, liver, and epididymis, and the weakest expression in the lung, spleen, uterus, and gut. In the male Harderian gland (HG), castration decreased FXN expression, while dihydrotestosterone (DHT) administration reestablished levels. FXN expression levels were higher in the male HG than the female HG. Expression levels in endocrine tissues showed a certain degree of sexual dimorphism; the transcript in the testis was significantly higher than those in the ovary. The effects of the estrous cycle on FXN expression remained unchanged in the HG, ovary, and adrenal glands; however, in the pancreas, the FXN mRNA was overexpressed during proestrus and exhibited sexual dimorphism as compared to the male pancreas. The mRNA expression results indicated that Harderian FXN may play a dynamic role in intracellular Fe of heme required for processing cytochromes and other hemeproteins, also suggesting that the moderate sexual dimorphism present in the HG and gonads could be regulated by androgens, while sexually dimorphic expression of FXN in the female pancreas may be controlled by sex steroids.