Lei Guo1, Yi-Xi Chen1, Yu-Ting Hu1, Xue-Yan Wu1, Yang He1, Juan-Li Wu1, Man-Li Huang2, Matthew Mason3, Ai-Min Bao4. 1. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, National Clinical Research Center for Mental Health Disorders, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P.R.China. 2. Department of Mental Health, First Affiliated Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Mental Health Disorders, Zhejiang Province Key Laboratory of Mental Disorder's Management, Hangzhou, P.R.China. 3. Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, KNAW, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. 4. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, National Clinical Research Center for Mental Health Disorders, Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, P.R.China. Electronic address: baoaimin@zju.edu.cn.
Abstract
BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.
BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD:Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.
Authors: Asta Mažeikienė; Svajone Bekesiene; Dovilė Karčiauskaitė; Eglė Mazgelytė; Gerry Larsson; Tomas Petrėnas; Andrius Kaminskas; Jurgita Songailienė; Algirdas Utkus; Ramutė Vaičaitienė; Rasa Smaliukienė Journal: Int J Environ Res Public Health Date: 2021-11-22 Impact factor: 3.390