Sex differences in the stress response: female rats are more sensitive — ASN Events
  1. Schedule
  2. Poster Session 2 - Neuroendocrinology of Stress II
  3. Sex differences in the stress response: female rats are more sensitive

Sex differences in the stress response: female rats are more sensitive (#370)

Jing Lu , Xue-Yan Wu , Qiong-Bin Zhu , Jia Li , Lei Guo , Li-Gen Shi , Juan-Li Wu , Ai-Min Bao 1
  1. Department of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

Background:  There are clear sex differences in human stress responses and depression1-5.  In order to determine the possible neurobiological basis for these differences we performed a systematic study of the sex difference in the rat hypothalamic molecular changes following acute foot shock (FS) and after chronic unpredictable stress (CUS). Methods: Female Sprague–Dawley rats were randomly divided into 6 groups: CUS rats sacrificed in proestrus or diestrus, FS rats sacrificed in proestrus or diestrus, and control rats sacrificed in proestrus or diestrus. Male Sprague–Dawley rats were also randomly divided into CUS, FS and control groups. Plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), as well as the hypothalamic mRNA-expression of stress-related molecules were measured, including estrogen receptor α and β (ERα, ERβ), androgen receptor (AR), aromatase (ARO), mineralocorticoid receptor (MR), glucocorticoid receptor (GR), corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and oxytocin (OXT). Results: Female CUS rats showed disordered estrus cycles, significantly increased plasma CORT, and decreased E2 and T plasma levels after FS or CUS. Rats in diestrus exhibited more significant changes in the hypothalamic stress-related molecules including ERβ, AR, GR and MR than those in proestrus phase. Male FS rats showed significantly increased plasma levels of CORT, a trend for increased E2 and no significant changes in T levels, while male CUS rats showed significantly increased CORT but decreased T levels. In addition, the male CUS rats only showed significantly increased AVP-mRNA expression in the hypothalamus. Conclusion:  A clear sex difference was found: female rats were more sensitive to stress, both in peripheral hormone levels and in the hypothalamic molecular changes. Comparisons with human data are discussed.

  1. Bao AM et al., Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders. Brain 2005; 128(Pt 6): 1301-1313.
  2. Bao AM et al., A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry 2006; 11(6): 567-576.
  3. Bao AM et al., The stress system in depression and neurodegeneration: focus on the human hypothalamus." Brain Res Rev 2008; 57(2): 531-553.
  4. Bangasser DA et al., Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology. Mol Psychiatry 2010; 15(9): 877, 896-904.
  5. Bao AM and Swaab DF. Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Front Neuroendocrinol 2011; 32(2): 214-226.