--- title: Does estrogen receptor expression change across the menstrual cycle in people with schizophrenia? description: In laboratory mice with schizophrenia-like conditions, a type of estrogen receptor called GPER was more active during the high-estrogen phase of the cycle. Ma url: https://niyora.com/research/papers/sex-and-the-estrous-cycle-phase-influence-the-expression-of-g-protein-coupled-2023/ --- - [Niyora](https://niyora.com/) - [Research](https://niyora.com/research/) - [Library](https://niyora.com/research/library/) - Does estrogen receptor expression change across the menstrual cycle in people with schizophrenia? Lab study, 2023 # Does estrogen receptor expression change across the menstrual cycle in people with schizophrenia? In laboratory mice with schizophrenia-like conditions, a type of estrogen receptor called GPER was more active during the high-estrogen phase of the cycle. Male mice and people with schizophrenia showed lower GPER levels. Early or limited evidence Laboratory mice with schizophrenia-like condition; blood cells from people with schizophrenia and healthy controls ## What they did Animal study with mice modeling schizophrenia. Female mice were examined during high and low-estrogen cycle phases. Male mice were also studied. Brain tissue was tested for estrogen receptors and proteins that make estrogen. Blood cells from people with schizophrenia and healthy people were converted to immune cells and tested for estrogen receptors. ## What they found Female mice during the high-estrogen phase of their cycle had higher levels of GPER (a type of estrogen receptor) in the brain and higher levels of proteins that make estrogen. These female mice did not have behavioral problems in a test called prepulse inhibition (which measures schizophrenia-like behavior). Male mice with the condition had lower levels of proteins that make estrogen and GPER, and showed prepulse inhibition deficits. Blood cells from both male and female people with schizophrenia had lower GPER than cells from healthy people. ## What it means for you This laboratory study in mice and cells suggests that estrogen receptor activity may be involved in sex differences in schizophrenia and in why women's symptoms change across the cycle. However, these are animal and cell studies, not research in living people, so the results may not directly apply to humans. 2 menstrual cycle phases studied in female mice ## About the study Original title Sex and the Estrous-Cycle Phase Influence the Expression of G Protein-Coupled Estrogen Receptor 1 (GPER) in Schizophrenia: Translational Evidence for a New Target Authors da Silva FER, Cordeiro RC, de Carvalho Lima CN et al. Journal Molecular neurobiology Year 2023 Study design Lab study What was tested None (observational study comparing naturally occurring differences) Open access Yes Read the paper [doi.org/10.1007/s12035-023-03295-x](https://doi.org/10.1007/s12035-023-03295-x) Original abstract Schizophrenia is a mental disorder with sex bias in disease onset and symptom severity. Recently, it was observed that females present more severe symptoms in the perimenstrual phase of the menstrual cycle. The administration of estrogen also alleviates schizophrenia symptoms. Despite this, little is known about symptom fluctuation over the menstrual cycle and the underlying mechanisms. To address this issue, we worked with the two-hit schizophrenia animal model induced by neonatal exposure to a virus-like particle, Poly I:C, associated with peripubertal unpredictable stress exposure. Prepulse inhibition of the startle reflex (PPI) in male and female mice was considered analogous to human schizophrenia-like behavior. Female mice were studied in the proestrus (high-estrogen estrous cycle phase) and diestrus (low-estrogen phase). Additionally, we evaluated the hippocampal mRNA expression of estrogen synthesis proteins; TSPO and aromatase; and estrogen receptors ERα, ERβ, and GPER. We also collected peripheral blood mononuclear cells (PBMCs) from male and female patients with schizophrenia and converted them to induced microglia-like cells (iMGs) to evaluate the expression of GPER. We observed raised hippocampal expression of GPER in two-hit female mice at the proestrus phase without PPI deficits and higher levels of proteins related to estrogen synthesis, TSPO, and aromatase. In contrast, two-hit adult males with PPI deficits presented lower hippocampal mRNA expression of TSPO, aromatase, and GPER. iMGs from male and female patients with schizophrenia showed lower mRNA expression of GPER than controls. Therefore, our results suggest that GPER alterations constitute an underlying mechanism for sex influence in schizophrenia. Reproduced under CC-BY. ## Topics [Schizophrenia and psychosis](https://niyora.com/research/topics/comorbidity-psychosis/)[Relationships and partners](https://niyora.com/research/topics/life-area-relationships/) Research tells you what helps on average. Niyora helps on the day it hits. Calm down, see it another way, and decide what to say, with a PMS and PMDD app built by a doctor. ## Related studies Survey study, 2025 Do women with PMS have higher anxiety, stress, and different personality traits? Case-control study, 2018 Do women with atopic dermatitis have more premenstrual syndrome than women without it? 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