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  • sn 38 mg br Vertebrate steroid receptor evolution br Conclus


    Vertebrate steroid receptor evolution
    Conclusion The teleost WGD event resulted in the duplication of the vertebrate GR and MR and two GRs have been retained in the majority of teleost fish studied so far. The molecular basis for this retention has yet to be fully understood. The cloning of the first GR2 and functional characteristic analysis of subsequent GR2 suggested that there is one mechanism for differential regulation of gene networks maybe via differences in the transcriptional activity sensitivity of the 2 GRs, (Bury et al., 2003). This maybe the case in the rainbow trout (Bury et al., 2003), carp (Stolte et al., 2007) and beloniforms (Kim et al., 2011, Miyagawa et al., 2015), but was not observed in a cichlidae (Greenwood et al., 2003) and thus is not a universal explanation for the retention of the two GRs. The only common feature is the 9 amino sn 38 mg insert in the teleost GR1 group. Very little work has been carried out to assess the significance of this insertion, but those studies that have suggest that the insertion does indeed affect transcriptional responses, however, this is dependent on species and the number of GRE upstream of reporter genes (Lethimonier et al., 2002, Greenwood et al., 2003, Miyagawa et al., 2015). An interesting observation is the effect of heterodimer formation in regulation of receptor function. In the earliest active SR reported from a cephalochordate, its transcriptional activity is repressed in the presences of a non-active ER (Fig. 3A, Bridgham et al., 2008). The ability to repress GR activity also appears to be of importance in vertebrates. In humans, a splice variant GRβ, which lacks the C-terminal region, is a negative-dominant repressor of GRα (Fig. 3B, Bamberger et al., 1996). In zebrafish, which have lost the second GR found in other teleost fishes, convergent evolution sees the emergence of a similar GRβ to that in humans that also acts as a repressor of zebrafish GRα activity (Fig. 3B, Schaaf et al., 2008). To date, the zebrafish are the only fish species known to have “human-like” GRβ, but GR activity repression may occurs via a different route in other fish species, with Kiilerich et al. (2015) showing that in rainbow trout the MR, which also binds cortisol and can activate GREs in vitro (Sturm et al., 2005), can act to repress GR1 and GR2 transactivation The retention of teleost GRs suggests some evolutionary advantage that saw the development of a more complex regulatory process to mediate the actions of glucocorticoids. This may be due to either difference between the GRs in their sensitivity to hormones, their DBD recognising different GREs, or heterodimer formation altering the functional properties and in doing so altering the ability to activate genes. However, the regulation of tissue specific GC actions maybe even more complex, due to the fact that a number of vertebrate GR proteins have been identified that lack portions of the NTD due to different translation initiation sites and post-translational modifications will affect functionality (Oakley and Cidlowski, 2011).
    Introduction Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition defined by the core symptoms of inattention, hyperactivity, and impulsivity. The biological mechanisms through which genetic and environmental factors act and interact to alter neurodevelopment in ADHD are controversial and remain largely unclear. In recent years, many studies have been focused on the genes that related to the dysregulation of monoamine neurotransmitters, and with further studies of nerve-endocrine-immune network, the interaction between monoamine systems and the hypothalamic-pituitary-adrenal axis (HPA) have gained increasingly attention (Liting, 2013). Most recent studies have suggested that the HPA axis of ADHD children is hypo-responses to stress, whereas hypo-responsiveness plays an important role in the three core symptoms of ADHD (Van et al., 2009). As the first one to study the relation between ADHD and HPA axis in China, we also found that the HPA axis was hypo-responses in ADHD children, and the level of plasma cortisol was low, demonstrating its close relationship to the symptom of attention deficit, hyperactivity and impulsive behavior (Ma and Chen, 2011).