精神障碍和治疗

The Role of the Androgen Receptor in Oxytocin Gene Expression: Implications for Mood Disorders

Abstract

Mirko Diksic

Oxytocin (OXT), which is synthesised in the hypothalamic paraventricular nucleus (PVN) and then released into various brain areas, may play an important role in a variety of behaviours and neuropsychiatric disorders, including depression. Clinical studies have suggested that testosterone has the opposite effect on these disorders as oxytocin. We began by looking at the expression of OXT in the PVN of fifteen patients with mood disorders and fifteen matched controls using immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) using double labelling ICC in the post-mortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls. Following that, the in vitro regulatory effect of AR on OXT gene expression was investigated. Scientist discovered that mood disorder patients had higher levels of PVN OXT expression than control subjects, and we saw a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. Furthermore, after pre-incubating the SK-N-SH cells with testosterone, OXT-mRNA levels were found to be significantly lower. Electrophoretic mobility shift assays and co-transfections in neuroblastoma cells revealed another potential androgen-responsive element in the human OXT gene promotor. Finally, in vitro studies revealed that AR mediated the suppression of OXT gene expression. These findings suggest that the fact that OXT and testosterone appear to have opposing effects in neuropsychiatric disorders may be due to a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.