Estrogen Receptor Beta Mediates the Dipsogenic Effect of Estradiol in Ovariectomized Female Rats

Introduction: Although the fluid inhibitory effects of estradiol are well characterized, a dipsogenic role of the hormone was recently identified. In ovariectomized (OVX) rats, unstimulated water intake, in the absence of food, was increased after estradiol treatment. Methods: The goals for these experiments were to further characterize the fluid enhancing effects of estradiol by determining the estrogen receptor subtype mediating the dipsogenic effect, examining saline intake, and testing for a dipsogenic effect of estradiol in male rats. Results: Pharmacological activation of estrogen receptor beta (ER beta) increased water intake, in the absence of food, and was associated with changes in postingestive feedback signals. Surprisingly, activation of ER alpha reduced water intake even in the absence of food. A follow-up study demonstrated that when food was available, co-activation of ER alpha and ER beta reduced water intake, but when food was not available water intake was increased. In addition, in OVX rats, estradiol increased saline intake through changes in postingestive and orosensory feedback signals. Finally, although estradiol decreased water intake in male rats with access to food, estradiol had no effect on water intake in the absence of food. Conclusions: These results demonstrate that the dipsogenic effect is mediated by ER beta, the fluid enhancing effects of estradiol generalize to saline, and is limited to females, which implies that a feminized brain is necessary for estradiol to increase water intake. These findings will aid in guiding future studies focused on elucidating the neuronal mechanisms that allow estradiol to both increase and decrease fluid intake.