Oestrogen effects on urine concentrating response in young women

Oestrogen lowers the plasma osmotic threshold for arginine vasopressin (AVP) release but without commensurate changes in renal concentrating response, suggesting oestrogen (OE 2 ) may lower renal sensitivity to AVP. Ten women (23 ± 1 years) received a gonadotropin releasing hormone analogue (GnRHa), leuprolide acetate, to suppress OE 2 for 35 days, and then added OE 2 (two patches each delivering 0.1 mg day −1 ) on days 32–35. On days 28 and 35 we tested blood and renal water and sodium (Na + ) regulation during stepwise 60 min AVP infusions (10, 35, 100, 150 and 200 μ u (kg body weight) −1 Pitressin). Plasma OE 2 concentration increased from 19 ± 4 to 152 ± 3 pg ml −1 and plasma progesterone concentration was unchanged (1.0 ± 0.4 and 0.7 ± 0.1 ng ml −1 ) for GnRHa and OE 2 administration, respectively. Standard log plots of plasma AVP concentration ([AVP] P ) vs. urine osmolality (Osm U ) were fitted to a sigmoidal curve, and EC 50 was determined by non‐linear regression curve fitting of concentration‐response data. Osm U rose exponentially during AVP infusions, but hormone treatments did not affect EC 50 (3.3 ± 0.07 and 3.1 ± 0.6 pg ml −1 , for GnRHa and OE 2 , respectively). However, the urine osmolality increase was greater within the physiological range (˜2.5−3.4 pg ml −1 [AVP] P ) during OE 2 treatment. Throughout most of the AVP infusion, the rate of clearance of AVP from plasma (PCR AVP ) was increased during OE 2 (45.5 ml (kg body weight) −1 min −1 ) compared to GnRHa administration (33.1 ml (kg body weight) −1 min −1 ; mean for the 100–200 μ u (kg body weight) −1 infusion rates). The rate of renal free water clearance ( C H2O ) was similar between hormone treatments. Sodium excretion fell during OE 2 administration due to greater distal tubular sodium reabsorption. Despite more rapid PCR AVP , renal concentrating response to graded AVP infusions was unaffected by oestrogen treatment suggesting oestrogen does not affect overall renal sensitivity to AVP. However, OE 2 may increase renal fluid retention within a physiological range of AVP.