Responses to a Saline Load in Gonadotropin-Releasing Hormone Antagonist-Pretreated Premenopausal Women Receiving Progesterone or Estradiol-Progesterone Therapy

John B. Pierce Laboratory, Department of Epidemiology, Yale University School of Medicine an Women and Infants Hospital, New Haven, Connecticut 06519, USA.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 02/2005; 90(1):386-94. DOI: 10.1210/jc.2004-0941
Source: PubMed


The effects of estradiol (E(2)) and progesterone (P(4)) on fluid and sodium regulation may have important clinical implications with respect to cardiovascular and renal disease as well as reproductive syndromes such as preeclampsia and ovarian hyperstimulation syndrome. We tested the hypothesis that sodium excretion is reduced in response to a sodium load during combined P(4)-E(2) treatment, but P(4) administration alone has little effect on sodium regulation. Fifteen women (22 +/- 2 yr) used a GnRH antagonist to suppress endogenous E(2) and P(4) for 9 d; for d 4-9, eight subjects used P(4) (200 mg/d), and seven subjects used P(4) with E(2) (two E(2) patches, 0.1 mg/d each). On d 3 and 9, isotonic saline (0.9% NaCl) was infused [120 min at 0.1 ml/kg body weight (BW).min], followed by 120 min of rest. Compared with GnRH antagonist alone, P([P4]) increased from 1.6 +/- 0.8 to 9.4 +/- 2.3 ng/ml (5.1 +/- 2.5 to 29.9 +/- 7.3 nmol/liter, P < 0.05) in the P(4) treated group, with no change in P([E2]). In the P(4)-E(2) treated group P([P4]) increased from 1.6 +/- 0.5 to 6.7 +/- 0.6 ng/ml (5.1 +/- 1.6 to 21.3 +/- 1.6 nmol/liter, P < 0.05 and P([E2]) increased from 17.9 +/- 6.3 to 200 +/- 41 pg/ml (65.7 +/- 23 to 734.6 +/- 150.0 pmol/liter, P < 0.05). Before isotonic saline infusion, renal sodium and water excretion were similar under all conditions, but during isotonic saline infusion, cumulative sodium excretion was lower in the P(4)-E(2) treated women (34.1 +/- 5.1 mEq) compared with GnRH antagonist (50.2 +/- 11.4 mEq). Sodium excretion was unaffected by P(4) treatment (48.0 +/- 8.2 and 41.2 +/- 5.1 mEq, for GnRH antagonist and P(4)). Compared with GnRH antagonist alone, P(4)-E(2) treatment increased distal sodium reabsorption and transiently decreased proximal sodium reabsorption, whereas P(4) treatment did not alter either distal or proximal sodium reabsorption. Before isotonic saline infusion, the plasma aldosterone (Ald) concentration was greater during P(4) treatment (153 +/- 25 pg/ml; 3883 +/- 1102 pmol/liter) and P(4)-E(2) treatment (242 +/- 47 pg/ml; 6373 +/- 1390 pmol/liter) than during their respective GnRH antagonist alone treatments [96 +/- 13 and 148 +/- 47 pg/ml (2598 +/- 475 and 3284 +/- 973 pmol/liter) for P(4) and combined P(4)-E(2), respectively]. Compared with GnRH antagonist alone treatments, preisotonic saline infusion plasma renin activity was greater only with P(4)-E(2) treatment, whereas the plasma atrial natriuretic peptide concentration was lower only with P(4) treatment. Isotonic saline infusion suppressed plasma Ald under all conditions, but decreased plasma renin activity only with P(4)-E(2) treatment (average decrease, 1.3 +/- 0.5 ng/ml angiotensin I.h; P < 0.05). In summary, we found that P(4)-E(2) treatment decreased sodium excretion via either renin-angiotensin-Ald system stimulation or direct effects on kidney tubules. P(4) treatment at these plasma concentrations had no independent effect on the renal response to acute sodium loading. These data suggest that E(2) is the more powerful reproductive hormone involved in sodium retention relative to P(4), and that estrogen-induced up-regulation of P(4) receptors is required for the effects of P(4) on sodium regulation.

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    • "Renal functions are controlled mainly by humoral factors and the sympathetic nervous system (such as catecholamine release), which differ widely in their time of activation (34). The complex interactions of different hormones, such as sex steroid hormones, atrial natriuretic factor, angiotensin II, aldosterone, and vasopressin, may affect tubular reabsorption and water intake (5,35,36). Furthermore, renal cells after oophorectomy and hormonal replacement adapt and alter the expression of several genes that code for transporter proteins (10,33,34). "
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    ABSTRACT: The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.
    Full-text · Article · Jul 2013 · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.]
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    • "In the present study, the increase in FE Na + and FE Cl – in gonadectomized groups, may be due to a decreased sodium/chloride carrier expression, caused by sex gonadal deficiency. This could result in decreased sodium reabsorption and increased natriuresis in this animal model (Burg et al. 1997; Stachenfeld et al. 2005). "
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    ABSTRACT: Several studies have demonstrated that gonadal hormones show significant effects on the brain and signaling pathways of effector organs/cells that respond to neurotransmitters. Since little information is available concerning the impact of male and female gonadal hormones on the renal and peripheral sympathetic system, the objective of this study was to further assess whether and how the renal content and plasma concentration of catecholamines are influenced by gender and the estrous cycle in rats. To achieve this, males Wistar rats were divided into 4 groups: (i) sham (i.e., control), (ii) gonadectomized, (iii) gonadectomized and nandrolone decanoate replacement at physiological levels or (iv) gonadectomized and nandrolone decanoate replacement at high levels. Female Wistar rats were divided into 6 groups: (i) ovariectomized (OVX), (ii) estrogen replacement at physiological levels and (iii) estrogen replacement at at high levels, (iv) progesterone replacement at physiological levels and (v) progesterone replacement at at high levels, and (vi) sham. The sham group was subdivided into four subgroups: (i) proestrus, (ii) estrus, (iii) metaestrus, and (iv) diestrus. Ten days after surgery, the animals were sacrificed and their plasma and renal catecholamine levels measured for intergroup comparisons. Gonadectomy led to an increase in the plasma catecholamine concentration in females, as well as in the renal catecholamine content of both male and female rats. Gonadectomized males also showed a lower level of plasma catecholamine than the controls. The urinary flow, and the fractional excretion of sodium and chloride were significantly increased in gonadectomized males and in the OVX group when compared with their respective sham groups.
    Full-text · Article · Jan 2012 · Canadian Journal of Physiology and Pharmacology
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    ABSTRACT: Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential for blood pressure and fluid regulation. We tested the hypotheses that combined progesterone (P(4))-estrogen (E(2)) administration would increase ECF volume with proportional increases in PV, but that P(4) would have little independent effect on either PV or ECF volume. We further hypothesized that this P(4)-E(2)-induced fluid expansion would be a function of renin-angiotensin-aldosterone system stimulation. We suppressed P(4) and E(2) with a gonadotropin-releasing hormone (GnRH) antagonist in eight women (25 +/- 2 yr) for 16 days; P(4) (200 mg/day) was added for days 5-16 (P(4)) and 17beta-estradiol (2 x 0.1 mg/day patches) for days 13-16 (P(4)-E(2)). On days 2 (GnRH antagonist), 9 (P(4)), and 16 (P(4)-E(2)), we estimated ECF and PV. To determine the rate of protein and thus water movement across the ECF, we also measured transcapillary escape rate of albumin. In P(4), P([P(4)]) increased from 2.5 +/- 1.3 to 12.0 +/- 2.8 ng/ml (P < 0.05) with no change in P([E(2)]) (21.5 +/- 9.4 to 8.6 +/- 2.0 pg/ml). In P(4)-E(2), plasma concentration of P(4) remained elevated (11.3 +/- 2.7 ng/ml) and plasma concentration of E(2) increased to 254.1 +/- 52.7 pg/ml (P < 0.05). PV increased during P(4) (46.6 +/- 2.5 ml/kg) and P(4)-E(2) (48.4 +/- 3.9 ml/kg) compared with GnRH antagonist (43.3 +/- 3.2 ml/kg; P < 0.05), as did ECF (206 +/- 19, 244 +/- 25, and 239 +/- 27 ml/kg for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05). Transcapillary escape rate of albumin was lowest during P(4)-E(2) (5.8 +/- 1.3, 3.5 +/- 1.7, and 2.2 +/- 0.4%/h for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05). Serum aldosterone increased during P(4) and P(4)-E(2) compared with GnRH antagonist (79 +/- 17, 127 +/- 13, and 171 +/- 25 pg/ml for GnRH antagonist, P(4), and P(4)-E(2), respectively; P < 0.05), but plasma renin activity and plasma concentration of ANG II were only increased by P(4)-E(2). This study is the first to isolate P(4) effects on ECF; however, the mechanisms for the ECF and PV expansion have not been clearly defined.
    Preview · Article · Jun 2005 · Journal of Applied Physiology
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