title: Effects of the estrous cycle and ovarian hormones on central expression of interleukin-1 evoked by stress in female rats.
abstract: Exposure to stressors such as foot shock (FS) leads to increased expression of multiple inflammatory factors, including the proinflammatory cytokine interleukin-1 (IL-1) in the brain. Studies have indicated that there are sex differences in stress reactivity, suggesting that the fluctuations in gonadal steroid levels across the estrous cycle may play a regulatory role in the stress-induced cytokine expression. The present studies were designed to investigate the role of 17-β-estradiol (E2) and progesterone (Pg) in regulating the cytokine response within the paraventricular nucleus (PVN) of the hypothalamus through analysis of gene expression with real-time RT-PCR. Regularly cycling female rats showed a stress-induced increase in PVN IL-1 levels during the diestrous, proestrous, and estrous stages. During the metestrous stage, no change in IL-1 levels was seen following FS; however, estrogen receptor (ER)-β levels did increase. Ovariectomy resulted in an increase in PVN IL-1 levels, which was attenuated by treatment with estradiol benzoate (10 or 50 µg), indicating an E2-mediated anti-inflammatory effect. Ovariectomized rats treated with Pg (500 or 1,250 µg) showed no alteration in IL-1 levels, but Pg did up-regulate ER-β gene expression. The results from the current study implicate a potential mechanism through which high availability of endogenous Pg during the metestrous stage increases ER-β sensitivity, which in turn attenuates the PVN IL-1 response to stress. Thus, the interaction between gonadal steroid hormones and their central receptors may exert a powerful inhibitory effect on neuroimmune consequences of stress throughout the estrous cycle.
authors.affiliation: Department of Psychology, State University of New York at Binghamton, Binghamton, N.Y., USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Arakawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arakawa
authors.forename: Cara M
authors.initials: CM
authors.lastname: Hueston
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004597:Electroshock; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000378:metabolism; D030762:Estrous Cycle / Q000378:metabolism*; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012102:Reproductive Control Agents / Q000494:pharmacology; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D047629:Estrogen Receptor beta; D007375:Interleukin-1; D012333:RNA, Messenger; D012102:Reproductive Control Agents; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol