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Striatal dopamine D2-type receptor availability and peripheral 17β-estradiol

Molecular Psychiatry volume 26, pages 2038–2047 (2021)Cite this article

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Abstract

Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17β-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17β-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23–45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17β-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

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Fig. 1: CONSORT diagram graphically depicting the overall flow of the study.
Fig. 2: Serum 17β-estradiol levels for each participant, each session, are depicted here.
Fig. 3: BPND values for each subject, each session, are shown here.

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Acknowledgements

This paper was made possible by the dedicated contributions of support staff including Maritza Johnson and Will Chu, and undergraduate student researchers including Brendan Bych, Sabina Fridman, and Jacqueline Rohde.

Funding

This work was supported by F32DA039715 (NP), the Marjorie Greene Family Trust, and the Thomas P and Katherine K Pike Chair in Addiction Studies (EDL).

Author information

Authors and Affiliations

  1. Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, 90095, USA

    Nicole Petersen, Kaitlin R. Kinney, Tomi Mizuno & Edythe D. London

  2. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, 90095, USA

    Nicole Petersen, Kaitlin R. Kinney, Tomi Mizuno & Edythe D. London

  3. Veterans Administration of Greater Los Angeles Health System, Los Angeles, CA, 90073, USA

    Nicole Petersen, Kaitlin R. Kinney, Mark A. Mandelkern & Edythe D. London

  4. Department of Obstetrics and Gynecology, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA

    Andrea J. Rapkin

  5. Department of Clinical Neuroimaging, Integrative Brain Imaging Center, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan

    Kyoji Okita

  6. Department of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8551, Japan

    Kyoji Okita

  7. Department of Physics, University of California at Irvine, Irvine, CA, 92697, USA

    Mark A. Mandelkern

  8. Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, 90095, USA

    Edythe D. London

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Petersen, N., Rapkin, A.J., Okita, K. et al. Striatal dopamine D2-type receptor availability and peripheral 17β-estradiol. Mol Psychiatry 26, 2038–2047 (2021). https://doi.org/10.1038/s41380-020-01000-1

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