ESTROGEN AND PROGESTERONE EFFECTS ON OSMOTIC FLUID REGULATION.

Abstract

PURPOSE: To determine the effect of estrogen on osmotic regulation of AVP and thirst; and on sodium regulation in young women. METHODS: We suppressed endogenous estrogen and progesterone production with the gonadotropin releasing-hormone (GnRH) analog, leuprolide acetate. Subjects were randomly assigned to one of two groups: one group received the GnRH analog alone followed by GnRH analog plus estrogen (E, n = 9, 25 ± 1 y); the other group received the GnRH analog alone followed by GnRH analog plus estrogen with progesterone (E/P, n = 6, 26 ± 3 y). Under all hormonal conditions, we compared AVP, thirst and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml/min/kg BW) followed by drinking (30 min, 15 ml/kg BW) and 90 min of recovery. RESULTS: In both groups (pooled), plasma [E2] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P4] increased from 0.6 to 6.4 ng/ml during E/P, and was unchanged (0.4 to 1.1 ng/ml) during E. During HSI, E reduced the plasma osmotic threshold for AVP release (275 ± 4 to 271 ± 4 mOsmol/kg, P < 0.05), although the thirst threshold was unaffected by E or E/P. Neither E nor E/P affected body water balance or CH2O. Relative to GnRH-alone, PRA was increased by E (0.8 ± 0.1 to 1.2 ± 0.2) and E/P (1.1 ± 0.2 to 2.5 ng/mg ANGI/h) at baseline. With E/P, PRA increased over rest during HSI (2.5 ng/mg ANGI/h, P < 0.05) and recovery (1.0 ± 0.6 ng/mg ANGI/h, P < 0.05), although there were no increase with E (0.6 ± 0.1 and 0.5 ± 0.1 ng/mg ANGI/h, for HSI and recovery respectively). Plasma [Ald] and [ANP] responses to HSI were unaffected by either E or E/P. Cumulative sodium excretion was attenuated in E (80 ± 17 to 74 ± 12 mEq) and E/P (90 ± 12 to 71 ± 10 mEq, P < 0.05) by the end of recovery. CONCLUSION: Estrogen increased osmotic release of AVP although without effects on renal water excretion, suggesting attenuated renal sensitivity to AVP. The lower sodium excretion during E compared to GnRH-alone, without concomitant changes in PRA or P[Ald], suggests direct effects of E on renal tubule sodium regulation. NIH RO 1 HL62240-01A1.