title: Aromatase changes in depression: A postmortem and animal experimental study.
abstract: A hyperactive hypothalamo-pituitary-adrenal (HPA) axis is a prominent feature in depression. It has been shown that androgens inhibit HPA activity and that estrogens stimulate it. We have therefore investigated, in human postmortem hypothalamus, whether depression features an increase in aromatase, which is the rate-limiting enzyme for the conversion of androgens to estrogens. In addition, we have tested the effect of an aromatase inhibitor on depression-like symptoms in a frequently used animal model for depression. At first, aromatase immunoreactivity (ir) was quantified in the central part of the hypothalamic paraventricular nucleus (PVN) of 10 major depressive disorder (MDD) patients and 10 well-matched control subjects. Subsequently an animal experimental study was performed using the chronic unpredictable mild stress (CUMS) rats as depression model. The effect of administration of 1,4,6-androstatriene-3,17-dione (ATD), an aromatase inhibitor, was investigated by silastic capsule implantation. In the postmortem study, the amount of PVN aromatase-ir decreased significantly in the MDD group compared to the controls (P=0.029). In the animal study, ATD was found to cause significantly increased testosterone (T) levels, both in plasma and in the hypothalamus. However, ATD administration did not show significant effects on the depression-like behaviors or plasma corticosterone levels in CUMS rats. Based on our observations in human postmortem material and the animal experiment, we have to conclude that alterations in aromatase in adulthood do not seem to play a major role in the pathogenesis of the symptoms of depression.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Juan-Li
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: He
authors.affiliation: Netherlands Institute for Neuroscience, an Institute of The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Radovan
authors.initials: R
authors.lastname: Hrubý
authors.affiliation: Netherlands Institute for Neuroscience, an Institute of The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Rawien
authors.initials: R
authors.lastname: Balesar
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yang-Jian
authors.initials: YJ
authors.lastname: Qi
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qiong-Bin
authors.initials: QB
authors.lastname: Zhu
authors.affiliation: Department of Mental Health, Zhejiang Province Key Laboratory of Mental Disorder's Management, National Clinical Research Center for Mental Health Disorders, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China; Netherlands Institute for Neuroscience, an Institute of The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: baoaimin@zju.edu.cn.
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Bao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000733:Androstatrienes / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: C115984:1,4,6-androstatrien-3,17-dione; D000733:Androstatrienes; D047072:Aromatase Inhibitors; D013739:Testosterone; D001141:Aromatase
keywords: 1,4,6-Androstatriene-3,17-dione; Aromatase; Chronic unpredictable mild stress; Depression; Paraventricular nucleus