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Oestrogen effects on urine concentrating response in young women

Nina S. Stachenfeld*†, Hugh S. Taylor*, Cheryl A. Leone* and David L. Keefe‡

Oestrogen lowers the plasma osmotic threshold for arginine vasopressin (AVP) release but without commensurate changes in renal concentrating response, suggesting oestrogen (OE₂) may lower renal sensitivity to AVP. Ten women (23 ± 1 years) received a gonadotropin releasing hormone analogue (GnRHa), leuprolide acetate, to suppress OE₂ for 35 days, and then added OE₂ (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 µu (kg body weight)^-1 Pitressin). Plasma OE₂ 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 OE₂ administration, respectively. Standard log plots of plasma AVP concentration ([AVP]_P) vs. urine osmolality (Osm_U) were fitted to a sigmoidal curve, and EC₅₀ 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 EC₅₀ (3.3 ± 0.07 and 3.1 ± 0.6 pg ml^-1, for GnRHa and OE₂, respectively). However, the urine osmolality increase was greater within the physiological range (~2.5-3.4 pg ml^-1 [AVP]_P) during OE₂ treatment. Throughout most of the AVP infusion, the rate of clearance of AVP from plasma (PCR_AVP) was increased during OE₂ (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 µu (kg body weight)^-1 infusion rates). The rate of renal free water clearance (C_H2O) was similar between hormone treatments. Sodium excretion fell during OE₂ 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, OE₂ may increase renal fluid retention within a physiological range of AVP.

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