Associate Dean for Research UNT Health Science Center Fort Worth, Texas, United States
Objectives: Hyponatremia, a common electrolyte disorder, is a particular concern in the rehabilitation setting. Studies have shown hyponatremia is associated with negative outcomes in various acute injuries (e.g., subarachnoid hemorrhage and exercise-induced hyponatremia) and chronic diseases (e.g., cirrhosis and congestive heart failure). Hyponatremia is an independent risk factor for increased mortality, resulting in a poorer prognosis in patients. Although hyponatremia associated with many of these conditions is related to inappropriate arginine vasopressin (AVP) release, knowledge gaps still exist about AVP release mechanisms particularly related to sex differences, which the present study aims to address.
Design: Our previous sex differences studies using an animal model of hyponatremia, bile duct ligation (BDL), showed female (intact and ovariectomized) BDL rats did not develop hyponatremia, AVP neuron activation, or increased plasma copeptin (a marker for AVP), compared to sham ligated females or male groups. Infusion of estrogen receptor (ER) antagonist, ICI 182,780 (ICI) in female BDL rats increased copeptin concentration compared to controls. These data suggest ER involvement in sex differences observed in female BDL rats. However, ICI is also a G protein-coupled estrogen receptor 1 (GPER) agonist. To test GPER expression within the hypothalamo-neurohypophyseal system of female rats, immunohistochemistry was performed on three separate sets of forebrain sections from each adult female Sprague-Dawley rat (n=6). All sets were processed for GPER, and either AVP, oxytocin (OXY), or glia fibrillary acidic protein (GFAP).
Results: Co-localization of GPER+AVP and GPER+OXY was observed in neurohypophyseal neurons (GPER+AVP, 64.8% and GPER+OXY, 64.0%). GPER+GFAP co-localization was not observed.
Conclusions: GPER is expressed on a subset of AVP and OXY neurons and not astrocytes in the hypothalamo-neurohypophyseal system of female rats. Future studies will provide further insight about role of ERs in sex differences in neurohypophyseal function and mortality risk in a preclinical model of hyponatremia.