Estrogen Receptor-α in the Medial Amygdala Prevents Stress-Induced Elevations in Blood Pressure in Females.
Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in female mice lacking estrogen receptor-α in the brain medial amygdala. Deletion of estrogen receptor-α in medial amygdala neurons also resulted in increased excitability of these neurons, associated with elevated ionotropic glutamate receptor expression. We further demonstrated that selective activation of medial amygdala neurons mimicked effects of stress to increase blood pressure in mice. Together, our results support a model where estrogen acts on estrogen receptor-α expressed by medial amygdala neurons to prevent stress-induced activation of these neurons, and therefore prevents pressor responses to stress.
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Antentor Othrell
AO
Hinton
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Yanlin
Y
He
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Yan
Y
Xia
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Pingwen
P
Xu
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Yongjie
Y
Yang
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Kenji
K
Saito
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Chunmei
C
Wang
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Xiaofeng
X
Yan
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Gang
G
Shu
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Alexander
A
Henderson
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Deborah J
DJ
Clegg
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Sohaib A
SA
Khan
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Corey
C
Reynolds
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Qi
Q
Wu
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.).
Qingchun
Q
Tong
From the Department of Pediatrics, Children's Nutrition Research Center (A.O.H., Y.H., Y.X., P.X., Y.Y., K.S., C.W., X.Y., G.S., A.H., Q.W., Y.X.), Advanced Technology/Core Laboratory (C.R.), and Department of Molecular and Cellular Biology (Y.X.), Baylor College of Medicine, One Baylor Plaza, Houston, TX; Department of Biomedical Research, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (D.J.C.); Department of Cell and Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati, College of Medicine, OH (S.A.K.); and Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (Q.T.). yongx@bcm.edu.
Yong
Y
Xu
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001795:Blood Pressure Determination; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D011960:Receptors, Estrogen / Q000378:metabolism*; D012016:Reference Values; D013312:Stress, Physiological
D011960:Receptors, Estrogen; D004958:Estradiol; D003345:Corticosterone
amygdala; blood pressure; estrogen; hypertension; neurons