A new study published in Molecular Genetics and Genomics found sexually dimorphic expression of frataxin (FXN), which plays a central role in Friedreich ataxia (FA), in the Harderian gland and endocrine tissues of hamsters. The study also suggests that sex steroids regulate FXN expression in hamsters.
“This sexual dimorphism associated with FXN in the hamster gonads contributes to the idea that reproductive tissues are the most sexually dimorphic tissues in the majority of mammals and clearly demonstrates the role of sex steroids in the transcriptional regulation of genes differentially expressed in each sex during development,” Luis Ramos, PhD, the author of the study, said.
Dr. Ramos detected higher levels of FXN in the Harderian gland and testes of male hamsters compared with the Harderian gland and ovaries of female hamsters.
Moreover, he found that castration decreased FXN expression in the male Harderian gland, suggesting that androgens could induce FXN expression and control iron homeostasis in hamsters. Conversely, the administration of dihydrotestosterone reestablished the expression levels of FXN.
Read more about FA etiology
FXN was overexpressed in the pancreas of female hamsters, although variations were observed during different phases of the reproductive cycle. The highest pancreatic levels of FXN were registered during the proestrus phase, whereas the lowest were during the estrus phase. Female hamsters in the proestrus phase showed higher pancreatic levels of FXN than male hamsters.
On the other hand, the expression levels of FXN in the Harderian gland, ovaries, and adrenal glands of female hamsters remained similar throughout all stages of the estrous cycle.
“The mRNA expression results indicated that Harderian FXN may play a dynamic role in intracellular [iron] of heme required for processing cytochromes and other hemeproteins, also suggesting that the moderate sexual dimorphism present in the [Harderian gland] and gonads could be regulated by androgens, while sexually dimorphic expression of FXN in the female pancreas may be controlled by sex steroids,” Dr. Ramos explained.
The FXN gene encodes the protein frataxin. Frataxin deficiency has been linked to increased iron deposition in the mitochondria and decreased activity of iron-sulfur cluster-containing subunits of mitochondrial respiratory chain complexes (I-III).
Ramos L. Dimorphic frataxin and its gene regulation by sex steroids in hamsters. Mol Genet Genomics. Published online March 16, 2023. doi:10.1007/s00438-023-02004-6