TY - JOUR T1 - Progesterone shapes medial temporal lobe volume across the human menstrual cycle JF - bioRxiv DO - 10.1101/2020.02.04.934141 SP - 2020.02.04.934141 AU - Caitlin M. Taylor AU - Laura Pritschet AU - Rosanna Olsen AU - Evan Layher AU - Tyler Santander AU - Scott T. Grafton AU - Emily G. Jacobs Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/02/05/2020.02.04.934141.abstract N2 - The rhythmic production of sex steroid hormones is a central feature of the mammalian endocrine system. In rodents and nonhuman primates, sex hormones are powerful regulators of hippocampal subfield morphology. However, it remains unknown whether intrinsic fluctuations in sex hormones alter hippocampal morphology in the human brain. In a series of dense-sampling studies, we used high-resolution imaging of the medial temporal lobe (MTL) to determine whether endogenous fluctuations (Study 1) and exogenous manipulation (Study 2) of sex hormones alter MTL volume over time. Across the menstrual cycle, intrinsic fluctuations in progesterone were associated with volumetric changes in CA2/3, entorhinal, perirhinal, and parahippocampal cortex. Chronic progesterone suppression abolished these cycle-dependent effects and led to pronounced volumetric changes in entorhinal cortex and CA2/3 relative to freely cycling conditions. No associations with estradiol were observed. These results establish progesterone’s ability to rapidly and dynamically shape MTL morphology across the human menstrual cycle.Significance Statement Estrogen and progesterone are powerful regulators of hippocampal plasticity in rodents and nonhuman primates, yet few human studies have established whether intrinsic fluctuations in sex hormones impact hippocampal morphology. Studies have conducted sparse-sampling or cross-sectional observations of women in different hormonal states, but these approaches fail to capture the dynamic endocrine changes that unfold over days, weeks, and months. In a series of dense-sampling studies using high resolution imaging of the medial temporal lobe (MTL), we discovered that endogenous fluctuations in progesterone across a complete menstrual cycle are associated with volumetric changes throughout MTL subregions. Chronic progesterone suppression abolishes these cycle-dependent changes. These findings establish progesterone’s ability to dynamically shape MTL volume in the human brain on an unprecedented timescale. ER -