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DHEAS and cortisol correlate with Hypothalamic Serotonin-1A Receptors

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Background

Serotonin modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, to a big part through the serotonin-1A receptor (5-HT1A) [1]. In return, hormones of the HPA axis, namely dehydroepiandrosterone sulfate (DHEAS) [2] and cortisol have regulatory effects on the serotonergic neurotransmission.

Materials and methods

Eighteen healthy female subjects participated in this PET study. The selective 5-HT1A receptor antagonist [carbonyl-11C]WAY-100635 was used as radioligand. The hypothalamus as an essential part of the HPA axis and eight control regions of interest and the cerebellum as reference region were defined a priori and delineated on co-registered MR images. DHEAS and cortisol plasma levels were ascertained by morning blood collections on the PET day. The 5-HT1A receptor binding potentials of the target brain regions were correlated with DHEAS, cortisol plasma levels and the ratio of DHEAS / cortisol.

Results

We found highly significant correlations between the hypothalamic 5-HT1A receptor binding and DHEAS (p=.003) and the ratio of DHEAS / cortisol (p<.0001), but not with cortisol and not in other brain regions.

Conclusions

The 5-HT1A receptor may influence the DHEAS plasma level by modulating CRH and ACTH release as reported for cortisol before [1]. Vice versa, the interaction of cortisol and DHEAS may exert a regulatory effect on the 5-HT1A receptor distribution in the hypothalamus as a feedback loop. As disturbances of the HPA axis [3] as well as changes of the 5-HT1A receptor distribution [4] have been reported frequently in affective disorders, future studies should aim their focus on these interactions.

References

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    Pan L, Gilbert F: Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces CRH and ACTH release in the rat. Neuroendocrinology. 1992, 56 (6): 797-802. 10.1159/000126332.

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    de Kloet ER, Joels M, Holsboer F: Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005, 6 (6): 463-75. 10.1038/nrn1683.

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    Christensen MV, Kessing LV: The hypothalamo-pituitary-adrenal axis in major affective disorder: a review. Nord J Psychiatry. 2001, 55 (5): 359-63. 10.1080/080394801317080873.

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    Parsey RV: Altered serotonin 1A binding in major depression: a [carbonyl-C-11] WAY100635 positron emission tomography study. Biol Psychiatry. 2006, 59 (2): 106-13. 10.1016/j.biopsych.2005.06.016.

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Acknowledgements

This research was supported by grants from the Austrian National Bank (OENB P11468) and the Medical Science Fund of the City of Vienna (BMF P2515) to R. Lanzenberger, and a grant from the Austrian Science Fund (FWF P16549). The authors are grateful to J. Tauscher, C. Windischberger, A. Becherer, N. Praschak-Rieder, L. Pezawas, M. Willeit, M. Fink, D. Ettlinger, T. Attarbaschi, S. Friedreich, E. Moser, and R. Dudczak for their scientific, medical or administrative support.

Author information

Correspondence to Ulrike Moser.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Cortisol
  • Cortisol Plasma Level
  • Dehydroepiandrosterone Sulfate
  • Healthy Female Subject
  • Receptor Binding Potential