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Direct Involvement of Androgen Receptor in Oxytocin Gene Expression : Possible Relevance for Mood Disorders. / Dai, Dan; Li, Qiao-Chu; Zhu, Qiong-Bin; Hu, Shao-Hua; Balesar, R.A.; Swaab, D.F.; Bao, Ai-Min.

In: Neuropsychopharmacology, Vol. 42, 08.2017, p. 2064-2071.

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Dai, Dan ; Li, Qiao-Chu ; Zhu, Qiong-Bin ; Hu, Shao-Hua ; Balesar, R.A. ; Swaab, D.F. ; Bao, Ai-Min. / Direct Involvement of Androgen Receptor in Oxytocin Gene Expression : Possible Relevance for Mood Disorders. In: Neuropsychopharmacology. 2017 ; Vol. 42. pp. 2064-2071.

BibTeX

@article{49fca7e6a6e843f4ae7d6f327c504f4f,
title = "Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders",
abstract = "Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and then released into different brain areas, may play a crucial role in various behaviors and neuropsychiatric disorders, including depression. Testosterone has been proposed by clinical studies to have the opposite effect of oxytocin in these disorders. We began by studying, in the postmortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls, the expression of OXT in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) by means of double labeling ICC. Subsequently, the regulatory effect of AR on OXT gene expression was studied in vitro. We found a higher expression of PVN OXT in the mood disorder patients than in the control subjects, and observed a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. In addition, a significant decrease in OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with testosterone. A further potential androgen-responsive element in the human OXT gene promotor was revealed by electrophoretic mobility shift assays and co-transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that AR mediated the down-regulation of OXT gene expression. These results suggest that the fact that OXT and testosterone appear to have opposite effects in neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.Neuropsychopharmacology accepted article preview online, 27 April 2017. doi:10.1038/npp.2017.76.",
keywords = "Journal Article",
author = "Dan Dai and Qiao-Chu Li and Qiong-Bin Zhu and Shao-Hua Hu and R.A. Balesar and D.F. Swaab and Ai-Min Bao",
year = "2017",
month = "8",
doi = "10.1038/npp.2017.76",
language = "English",
volume = "42",
pages = "2064--2071",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Direct Involvement of Androgen Receptor in Oxytocin Gene Expression

T2 - Possible Relevance for Mood Disorders

AU - Dai, Dan

AU - Li, Qiao-Chu

AU - Zhu, Qiong-Bin

AU - Hu, Shao-Hua

AU - Balesar, R.A.

AU - Swaab, D.F.

AU - Bao, Ai-Min

PY - 2017/8

Y1 - 2017/8

N2 - Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and then released into different brain areas, may play a crucial role in various behaviors and neuropsychiatric disorders, including depression. Testosterone has been proposed by clinical studies to have the opposite effect of oxytocin in these disorders. We began by studying, in the postmortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls, the expression of OXT in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) by means of double labeling ICC. Subsequently, the regulatory effect of AR on OXT gene expression was studied in vitro. We found a higher expression of PVN OXT in the mood disorder patients than in the control subjects, and observed a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. In addition, a significant decrease in OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with testosterone. A further potential androgen-responsive element in the human OXT gene promotor was revealed by electrophoretic mobility shift assays and co-transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that AR mediated the down-regulation of OXT gene expression. These results suggest that the fact that OXT and testosterone appear to have opposite effects in neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.Neuropsychopharmacology accepted article preview online, 27 April 2017. doi:10.1038/npp.2017.76.

AB - Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and then released into different brain areas, may play a crucial role in various behaviors and neuropsychiatric disorders, including depression. Testosterone has been proposed by clinical studies to have the opposite effect of oxytocin in these disorders. We began by studying, in the postmortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls, the expression of OXT in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) by means of double labeling ICC. Subsequently, the regulatory effect of AR on OXT gene expression was studied in vitro. We found a higher expression of PVN OXT in the mood disorder patients than in the control subjects, and observed a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. In addition, a significant decrease in OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with testosterone. A further potential androgen-responsive element in the human OXT gene promotor was revealed by electrophoretic mobility shift assays and co-transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that AR mediated the down-regulation of OXT gene expression. These results suggest that the fact that OXT and testosterone appear to have opposite effects in neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.Neuropsychopharmacology accepted article preview online, 27 April 2017. doi:10.1038/npp.2017.76.

KW - Journal Article

U2 - 10.1038/npp.2017.76

DO - 10.1038/npp.2017.76

M3 - Article

VL - 42

SP - 2064

EP - 2071

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

ER -

ID: 4204740