Estrogen receptors ERα and ERβ participation in hypothalamus-pituitary-adrenal axis activation by hemorrhagic stress

- Gradual moderate hemorrhage increased corticosterone secretion, and ERα and ERβ receptor activation inhibited this response.
- ERα agonist (PPT) treatment decreased corticosterone secretion in both control and hemorrhage situations.
- ERβ agonist (DPN) treatment decreased corticosterone secretion only after hemorrhagic stress.
- CRH neuron expression in paraventricular nucleus decreased after PPT or DPN treatment in rats with or without hemorrhage.
- PPT or DPN treatment in rats with or without hemorrhage decreased CRH neuron expression in the paraventricular nucleus.

The sympato-adrenal-system and hypothalamus-pituitary-adrenal (HPA) axis are anatomically and functionally connected with participation of several brain areas that express estrogen receptors (ERα and ERβ). We assessed the neuronal activity of these areas for FOS expression and the action of PPT (ERα agonist) or DPN (ERβ agonist) in HPA axis activity during hemorrhagic stress. Ovariectomized Wistar rats treated with vehicle (DMSO) or ER agonists were catheterized for blood collection. Animals received (control) or not (hemorrhagic) immediate reposition with the same volume of saline. Immunohistochemistry was performed for FOS, tyrosine hydroxylase (TH) and corticotropin releasing hormone (CRH) in the brain areas. In vehicle-treated animals, hemorrhage enhanced: plasma corticosterone (CORT), oxytocin (OT) and vasopressin (AVP) measured by radioimmunoassay; the expression of TH-FOS co-localized neurons in ventrolateral medulla (A1C1) and FOS expression in medial parvocellular paraventricular nucleus (mpPVN). In controls, PPT decreased: plasma CORT; FOS expression at locus coeruleus (LC); FOS and CRH-FOS at mpPVN, compared to vehicle. After hemorrhage, PPT decreased: plasma CORT; FOS expression at LC and mpPVN; TH-FOS at LC, solitary tract nucleus (NTS), A1C1; CRH-FOS at mpPVN, compared to vehicle. After hemorrhage DPN decreased: plasma CORT; FOS expression at LC and mpPVN; TH-FOS at LC, A1C1; CRH-FOS at mpPVN, compared to vehicle. PPT blocked the increase of OT secretion and increased AVP secretion, after hemorrhage. DPN reduced OT and increased AVP levels, regardless hemorrhage. In hemorrhagic stress, ERα and ERβ reduced the HPA axis activation and neuronal activity in brain areas involved in the HPA axis control.