title: Intrahypothalamic estradiol modulates hypothalamus-pituitary-adrenal-axis activity in female rats.
abstract: Estrogen plays an important role in the regulation of the hypothalamus-pituitary-adrenal (HPA)-axis, but the neuroendocrine pathways and the role of estrogen receptor (ER) subtypes involved in specific aspects of this interaction remain unknown. In a first set of experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, and by intrahypothalamic microdialysis to ovariectomized rats to measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion of E2 did not increase plasma CORT, but intracerebroventricular E2 induced a 3-fold CORT increase (P = 0.012). Local E2 infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (P < 0.001). A similar CORT increase was seen after PVN infusion of the ERα agonist propylpyrazoletriol, whereas the ERβ agonist diarylpropiolnitrile had no effect. In a second set of experiments, we investigated whether E2 modulates the HPA-axis response to acute stress by administering E2 agonists or its antagonist ICI 182,780 into the PVN during restraint stress exposure. After 30 min of stress exposure, plasma CORT had increased 5.0-fold (P < 0.001). E2 and propylpyrazoletriol administration in the PVN enhanced the stress-induced plasma CORT increase (8-fold vs. baseline), whereas ICI 182,780 and diarylpropiolnitrile reduced it, as compared with both E2 and vehicle administration in the PVN. In conclusion, central E2 modulates HPA-axis activity both in the basal state and during restraint stress. In the basal condition, the stimulation is mediated by ERα-sensitive neurons, whereas during stress, it is mediated by both ERα and ERβ.
authors.affiliation: Chinese Academy of Science Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Jinzhai Road 96, Hefei 230026, Anhui, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: P H
authors.initials: PH
authors.lastname: Bisschop
authors.forename: L
authors.initials: L
authors.lastname: Eggels
authors.forename: E
authors.initials: E
authors.lastname: Foppen
authors.forename: E
authors.initials: E
authors.lastname: Fliers
authors.forename: J N
authors.initials: JN
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Kalsbeek
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010636:Phenols; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D000077267:Fulvestrant; D004958:Estradiol; D003345:Corticosterone