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Am J Physiol Endocrinol Metab 283: E711-E721, 2002; doi:10.1152/ajpendo.00192.2002
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Vol. 283, Issue 4, E711-E721, October 2002

Estrogen effects on osmotic regulation of AVP and fluid balance

Nina S. Stachenfeld and David L. Keefe

The John B. Pierce Laboratory and Departments of Epidemiology and Public Health, Yale University School of Medicine and Women and Infants Hospital, Brown University School of Medicine, New Haven, Connecticut 06519

To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP) and body fluids, we suppressed endogenous estrogen and progesterone using the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n = 9, 25 ± 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n = 6, 26 ± 3). During GnRHa alone and with hormone treatment, we compared AVP and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml · min-1 · kg body wt-1), drinking (30 min, 15 ml/kg body wt), and recovery (60 min of seated rest). Plasma [E2] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P4] increased from 0.6 to 5.7 ng/ml during E/P and was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced osmotic AVP release threshold (275 ± 4 to 271 ± 4 mosmol/kg, P < 0.05), and E/P reduced the AVP increase in response during HSI (6.0 ± 1.3 to 4.2 ± 0.6 pg/ml at the end of HSI), but free water clearance was unaffected in either group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during E (0.8 ± 0.1 vs. 1.2 ± 0.2 ng ANG I · ml-1 · h-1) but not after HSI or recovery. PRA was greater than GnRHa during E/P at baseline (1.1 ± 0.2 vs. 2.5 ± 0.6) and after HSI (0.6 ± 0.1 vs. 1.1 ± 1.1) and recovery (0.5 ± 0.1 vs. 1.3 ± 0.2 ng ANG I · ml-1 · h-1). Baseline fractional excretion of sodium was unaffected by E or E/P but was attenuated by the end of recovery for both E (3.3 ± 0.6 vs. 2.4 ± 0.4%) and E/P (2.8 ± 0.4 vs 1.7 ± 0.4%, GnRHa alone and with hormone treatment, respectively). Fluid retention increased with both hormone treatments. Renal sensitivity to AVP may be lower during E due to intrarenal effects on water and sodium excretion. E/P increased sodium retention and renin-angiotensin-aldosterone stimulation.

body fluid regulation; arginine vasopressin; osmolality; thirst; gonadotropin-releasing hormone agonist; luprolide acetate


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