Cortisol resistance in the degu (Octodon degus)

Cortisol resistance has also been reported in the degu, Octodon degus, a New World hystricomorph endemic to central Chile. The degu is used as a model for studies of stress and diurnal rhythms, parental behaviour and female masculinization. Another New World hystricomorph, the guinea pig, also exhibits glucocorticoid resistance, a result of amino acid sequences that differ from other mammalian glucocorticoid receptors (GR). Mutations in the ligand-binding domain of the human GR have been identified in familial or sporadic generalised cortisol resistance as have variants in the guinea pig. To address the possibility that the high levels of cortisol observed in the degu are a result of the same or similar sequence variations observed in the guinea pig GR, we have cloned, expressed and characterised the ligand-binding domain (LBD) of the degu GR. Somewhat unexpectedly, neither the amino acids nor the region involved in the resistance observed in the guinea pig GR are relevant in the degu GR. The relative resistance to cortisol observed in the degu GR is conferred by the substitution of two isoleucine residues, which are highly conserved in the GR across species, with a valine doublet. These amino acids lie in the region between helices 5 and 6 of the GR LBD, a region known to be important in determining the affinity of ligand-binding in steroid receptors.

Automated summary

Cortisol resistance has been observed in degus, a type of New World hystricomorph endemic to central Chile. Degus are commonly used in studies related to stress, diurnal rhythms, parental behavior, and female masculinization. Similar to the guinea pig, another type of New World hystricomorph, degus also exhibit glucocorticoid resistance due to different amino acid sequences in their glucocorticoid receptors (GR). However, the specific amino acids and regions responsible for resistance in guinea pig GR are not applicable to degu GR. Instead, the resistance to cortisol in degu GR is caused by the substitution of two isoleucine residues with a valine doublet in the region between helices 5 and 6 of the GR ligand-binding domain (LBD).