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.
Highlights
In animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can exhibit an inverted U-shaped function
E2 valerate in doses of 0, 2, 4, 6 or 12 mg were orally administered on two consecutive days to 125 naturally cycling women during the low-hormone menstruation phase. This E2 treatment regimen induced a wide range of E2 levels, from physiological to supraphysiological on the second day. This wide range enabled us to test our hypothesis that the dose-response function between E2 and neural activity assessed by functional magnetic resonance imaging (MRI) increases monotonically within physiological ranges and turns into an inverted U-shape only at supraphysiological levels
We identified different patterns in which hippocampal activity responded to E2 dose: we found an inverted U-shape in the medial posterior hippocampus but a monotonically increasing dose-response function across the full range of E2 levels in the lateral posterior hippocampus
Summary
17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can exhibit an inverted U-shaped function. E2 valerate in doses of 0, 2, 4, 6 or 12 mg were orally administered on two consecutive days to 125 naturally cycling women during the low-hormone menstruation phase This E2 treatment regimen induced a wide range of E2 levels, from physiological (within 2and 4-mg groups; equivalent to cycle peak) to supraphysiological (within 6- and 12-mg groups; equivalent to early pregnancy) on the second day. This wide range enabled us to test our hypothesis that the dose-response function between E2 and neural activity assessed by functional MRI (fMRI; as a proxy for changes in neural plasticity) increases monotonically within physiological ranges and turns into an inverted U-shape only at supraphysiological levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
