Linear and inverted U-shaped dose-response functions describe estrogen effects on hippocampal activity in young women

Janine Bayer (), Jan Gläscher, Jürgen Finsterbusch, Laura H. Schulte and Tobias Sommer
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Janine Bayer: University Medical Center Hamburg-Eppendorf
Jan Gläscher: University Medical Center Hamburg-Eppendorf
Jürgen Finsterbusch: University Medical Center Hamburg-Eppendorf
Laura H. Schulte: University Medical Center Hamburg-Eppendorf
Tobias Sommer: University Medical Center Hamburg-Eppendorf

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract In animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can also exhibit an inverted U-shaped function. To investigate E2’s dose-response function in the human hippocampus, we pharmacologically increased E2 levels in 125 naturally cycling women (who were in their low-hormone menstruation phase) to physiological (equivalent to menstrual cycle peak) and supraphysiological (equivalent to levels during early pregnancy) concentrations in a placebo-controlled design. Twenty-four hours after first E2 intake, we measured brain activity during encoding of neutral and negative pictures and then tested recognition memory 24 h after encoding. Here we report that E2 exhibits both a monotonically increasing relationship with hippocampal activity as well as an inverted U-shaped relationship, depending on the hippocampal region. Hippocampal activity exhibiting a U-shaped relationship inflects at supraphysiological E2 levels, suggesting that while E2 within physiological ranges stimulates hippocampal activity, supraphysiological ranges show opposite effects.

Date: 2018
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DOI: 10.1038/s41467-018-03679-x

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