Role Of Estrogen In The Urinary Concentrating Mechanism

The anti‐diuretic hormone, arginine vasopressin (AVP) concentrates urine by enhancing water, salt and urea re‐absorption in the renal collecting duct. We hypothesized that estrogen may play a key role in the response of the renal collecting duct to AVP. We used CD1 male and female mice (8‐weeks old, n=8–10) and water restricted (WR, 48 hr) to increase endogenous AVP levels. In another study, we used CD1 female mice which were ovariectomized (OVX) for 5 weeks. Urine osmolality in WR female mice (4874 mOsm/kg.H 2 0) compared to WR males (3962 mOsm/kg.H 2 O) was significantly higher (25%). Consistent with elevated AVP levels during WR, medullary AQP2 was significantly increased in females (mRNA, 2.12‐fold and protein, 151%). However, following ovariectomy neither AQP2 nor AQP3 mRNA expression levels were altered versus control mice. WR had a similar response in either gender in increasing medullary mRNA expression of the urea transporters (UTA1, UTA3) but decreasing the sodium channels (ENaCβ and ENaCγ). Our data suggests that females are more sensitive to the actions of AVP in the renal medulla which results in higher water re‐absorption from urine possibly through increased expression of AQP2 channels leading to higher urine osmolality. However loss of estrogen (OVX) is not associated with a change in AQP2 expression in females. Support: DK073611 (HLB), NSF ADVANCE (HLB, JF) and HL07249 (SC).