FEMALE SEX-HORMONES INHIBIT VOLUME REGULATION IN RAT-BRAIN ASTROCYTE CULTURE

To determine whether sex steroids play any role in the increased morbi dity associated with acute symptomatic hyponatremia in menstruant fema les, we studied the actions of estradiol, progesterone, and testostero ne on regulatory volume decrease (RVD) of brain astrocytes in culture. To determine intracellular space with the use of 3-O-[methyl-D-H-3] g lucose, cells were cultured in media containing either estradiol or pr ogesterone. Those treated with ouabain were unable to regulate volume normally, whereas testosterone-treated cells displayed normal RVD. Aft er 15 s of hypotonic exposure, control cell volume and 100 nM testoste rone-treated cell volume increased by 26 and 31%, respectively. Cell v olume in control cells changed from 1.74 +/- 0.24 to 2.41 +/- 0.28 mu l/mg protein. At the same time, cells treated with either 10 nM estrad iol or 10 nM progesterone significantly (P < 0.01) increased their vol ume by 129 and 90%, respectively. Both the antiestrogen agent tamoxife n and the antiprogesterone agent mifepristone (RU-486) blocked the eff ects of estradiol and progesterone. The Na-K-ATPase pump, which plays an important role in cell RVD, was significantly (P < 0.03) inhibited by 32 and 21% in estradiol- and progesterone-treated cells, but signif icantly (P < 0.001) stimulated (49%) by testosterone treatment. Taken together, these results provide a possible explanation for the increas ed morbidity associated with acute symptomatic hyponatremia in menstru ant females.