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 (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 microu (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 (OsmU) were fitted to a sigmoidal curve, and EC50 was determined by non-linear regression curve fitting of concentration-response data. OsmU 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 (approximately 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 (PCRAVP) 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 microu (kg body weight)(-1) infusion rates). The rate of renal free water clearance (CH2O) was similar between hormone treatments. Sodium excretion fell during OE2 administration due to greater distal tubular sodium reabsorption. Despite more rapid PCRAVP, 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.
Stachenfeld
Nina S
NS
The John B. Pierce Laboratory, New Haven, CT 06519, USA. nstach@jbpierce.org
Taylor
Hugh S
HS
Leone
Cheryl A
CA
Keefe
David L
DL
D000279:Administration, Cutaneous; D000328:Adult; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000097:blood; D001834:Body Water / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology*; D016729:Leuprolide / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D014556:Urine / Q000737:chemistry
D004965:Estrogen Antagonists; D004967:Estrogens; D001127:Arginine Vasopressin; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide