Progesterone does not alter osmotic regulation of AVP.

To test the hypothesis that progesterone, independent of estrogen, decreases the plasma osmotic threshold for arginine vasopressin (AVP) release and thirst onset, we compared AVP and thirst responses to hypertonic saline infusion (HSI) during administration of oral contraceptives (OCs) containing progesterone (OCP) with responses to infusion of OCs containing progesterone and estrogen (OCEP). Eight women (29 +/- 2 yr) were infused with 3% NaCl (120 min, 0.1 ml. kg body wt(-1). min(-1)) and consumed fluid (90 min, 15 ml/kg body wt) in the early follicular and midluteal phases of a 28-day menstrual cycle and also after 4 wk of OCP and after 4 wk of OCEP in a randomized crossover design. Baseline plasma osmolality (P(osm)) was lower in the luteal phase (280 +/- 1 mosmol/kgH(2)O) and during OCEP (283 +/- 1 mosmol/kgH(2)O) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, P < 0.05) but was unaffected by OCP (284 +/- 1 mosmol/kgH(2)O). P(osm) remained lower in the follicular phase than in the luteal phase and with OCEP throughout the first 50 min of HSI. The mean abscissal plasma AVP concentration-P(osm) intercept was unaffected by OCP (267 +/- 1 mosmol/kgH(2)O) but was greater in the follicular phase (273 +/- 2 mosmol/kgH(2)O) than in the luteal phase (266 +/- 4 mosmol/kgH(2)O) and with OCEP (268 +/- 2 mosmol/kgH(2)O, P < 0.05). There were no differences in osmotic thresholds for thirst onset across experimental days. Despite the lower osmotic threshold for AVP release during the luteal phase and with OCEP, fluid balance, renal free water clearance, and Na(+) regulation during HSI were unaffected by menstrual phase or OC treatment, indicating a lower osmotic operating point for body water balance. OCP did not affect osmotic AVP regulation, suggesting that progesterone does not affect osmotic fluid regulation through a mechanism independent of estrogen.

Sex differences in osmotic regulation of AVP and renal sodium handling.

To determine sex differences in osmoregulation of arginine vasopressin (AVP) and body water, we studied eight men (24 +/- 1 yr) and eight women (29 +/- 2 yr) during 3% NaCl infusion [hypertonic saline infusion (HSI); 120 min, 0.1 ml. kg body wt(-1). min(-1)]. Subjects then drank 15 ml/kg body wt over 30 min followed by 60 min of rest. Women were studied in the early follicular (F; 16.1 +/- 2.8 pg/ml plasma 17beta-estradiol and 0.6 +/- 0.1 ng/ml plasma progesterone) and midluteal (L; 80.6 +/- 11.4 pg/ml plasma 17beta-estradiol and 12.7 +/- 0.7 ng/ml plasma progesterone) menstrual phases. Basal plasma osmolality was higher in F (286 +/- 1 mosmol/kgH(2)O) and in men (289 +/- 1 mosmol/kgH(2)O) compared with L (280 +/- 1 mosmol/kgH(2)O, P < 0.05). Neither menstrual phase nor gender affected basal plasma AVP concentration (P([AVP]); 1.7 +/- 4, 1.9 +/- 0.4, and 2.2 +/- 0.5 pg/ml for F, L, and men, respectively). The plasma osmolality threshold for AVP release was lowest in L (x-intercept, 263 +/- 3 mosmol/kgH(2)O, P < 0.05) compared with F (273 +/- 2 mosmol/kgH(2)O) and men (270 +/- 4 mosmol/kgH(2)O) during HSI. Men had greater P([AVP])-plasma osmolality slopes (i.e., sensitivity) compared with F and L (slopes = 0.14 +/- 0.04, 0.09 +/- 0.01, and 0.24 +/- 0.07 for F, L, and men, respectively, P < 0.05). Despite similar Na+-regulating hormone responses, men excreted less Na+ during HSI (0.7 +/- 0.1, 0.7 +/- 0.1, and 0.5 +/- 0.1 meq/kg body wt for F, L, and men, respectively, P < 0.05). Furthermore, men had greater systolic blood pressure (119 +/- 5, 119 +/- 5, and 132 +/- 3 mmHg for F, L, and men, respectively, P < 0.05) than F and L. Our data indicate greater sensitivity in P([AVP]) response to changes in plasma osmolality as the primary difference between men and women during HSI. In men, this greater sensitivity was associated with an increase in systolic blood pressure and pulse pressure during HSI, most likely due to a shift in the pressure-natriuresis curve.