Estrogen effects on osmotic regulation of AVP and fluid balance.
Abstract
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 [E 2 ] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P 4 ] 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.
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Sex differences are present in the activity and stimulus of the cell bodies of the periventricular nuclei and the supraoptic nuclei (located in the anterior hypothalamus), where arginine vasopression is synthesized.
“sex differences are present in the activity and stimulus of the cell bodies of the periventricular nuclei and the supraoptic nuclei (located in the anterior hypothalamus), where arginine vasopression is synthesized [266,267].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [267]
AVP and thirst are highly sensitive to plasma osmolality, needing only a 2%-3% change to increase.
“Arginine vasopressin and thirst are highly sensitive to changes in plasma osmolality, requiring only a 2%–3% change in osmolality to induce thirst or AVP increases (4,23,26).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [23]
Estrogens tend to raise plasma volume, whereas progesterone tends to lower it, through effects on capillary fluid dynamics or Starling forces.
“Estrogens tend to increase, whereas progesterone tends to decrease, plasma volume (22,23,25) through effects on capillary fluid dynamics or Starling forces (18,24,30).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [23]
For the most part, the authors' studies show that increases in sodium retention are independent of RAAS stimulation or ANP.
“For the most part, our studies have shown that increases in sodium retention are independent of RAAS stimulation or ANP (23,25).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [23]
The small but consistent water retention with estradiol administration may result from greater sodium retention rather than from AVP-induced increases in free water retention.
“We suspect that the small but consistently present water retention associated with estradiol administration may be a function of greater sodium retention rather than AVP-induced increases in free water retention (23,25).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [23]
Estrogens and progesterone increase renal sodium reabsorption, so plasma volume increases partly reflect ECF volume expansion, but plasma volume appears to increase disproportionately to ECF volume.
“Because estrogens and progesterone increase renal sodium reabsorption (23,25), the plasma volume increases are a function of ECF volume expansion to some extent, but plasma volume seems to increase disproportionally to ECF volume (27).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [23]
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References 48 · Cited by 126
- Authors
- Stachenfeld, N. S., & Keefe, D. L.
- Affiliations
- Brown University (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2002-10-01
- Volume
- 283
- Issue
- 4
- Pages
- E711-E721
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2141390128
- Semantic Scholar
- 244ca93de183e0b8ebb39fa73ec9243940ce6862
- Cited by
- 126
- References
- 48
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 12 · 2020: 6 · 2019: 4 · 2018: 5 · 2016: 5 · 2015: 9 · 2014: 8 · 2013: 4 · 2012: 5
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01-HL-62240-01A1, R01HL062240)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- estrogen, vasopressin, osmoregulation, fluid balance, sodium chloride infusion, free water clearance, plasma renin activity, aldosterone, progesterone, leuprolide, GnRH analogues, plasma estradiol, plasma progesterone, fractional excretion of sodium
- MeSH terms
- Adult, Arginine Vasopressin, Body Fluids, Drinking, Estrogens, Female, Fertility Agents, Female, Humans, Gonadotropin-Releasing Hormone, Progesterone, Sodium, Dietary, Thirst, Urine, Water-Electrolyte Balance, Leuprolide
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