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Go Red Brief Reviews

Sex Steroids and Renal Disease

Lessons From Animal Studies

Licy L. Yanes, Julio C. Sartori-Valinotti, Jane F. Reckelhoff
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https://doi.org/10.1161/HYPERTENSIONAHA.107.105767
Hypertension. 2008;51:976-981
Originally published March 19, 2008
Licy L. Yanes
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Julio C. Sartori-Valinotti
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Jane F. Reckelhoff
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  • Article
    • Estradiol and the Kidney
    • Progesterone and the Kidney
    • Testosterone and the Kidney
    • Diabetes, Hyperlipidemia, and Sex Steroids
    • Hypertension and Sex Steroids
    • Sex Steroids and Renin-Angiotensin System
    • Sex Steroids and Endothelin
    • Sex Steroids and Oxidative Stress
    • Perspectives
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Epidemiological studies have shown that male sex is an independent risk factor for the development and progression of renal disease, and men progress to end stage renal disease (ESRD) faster than premenopausal women in such diseases as autoimmune glomerulonephritis, hypertensive glomerulosclerosis, and polycystic kidney disease.1–3 Although the age-related decline in renal function is also faster in men, women become more susceptible to renal diseases after menopause.4 Insight from in vitro studies and animal models suggest that sex steroids play pivotal roles in modifying the progression to ESRD. Because there is a paucity of data in humans showing the mechanisms by which sex steroids impact renal disease, most of the studies discussed this review will be in animals, mainly rats. Furthermore, determining the roles of sex steroids in various diseases has been done using gonedectomized animals; however, although gonadectomy removes more than sex steroids and most studies only replace the sex steroid of interest, these are still the best studies in which to evaluate mechanisms responsible for sex differences in renal disease. Studies in postmenopausal women will also be kept to a minimum in this review because it is likely that sex steroids change action with aging, as suggested by the Women’s Health Initiative study.

Estradiol and the Kidney

Estrogen receptors (ER) are present in the kidney, although their localization in nephron segments has not been fully elucidated. Mesangial cells contain both ERα and ERβ,5 as do endothelium and vascular smooth muscle cells.5–7 Whether the newly described transmembrane estrogen receptor, GPR30,8 is present in kidneys has not been determined. Ovariectomy (ovx) of Dahl salt sensitive rats (DS) caused decreases in ERα but increases in ERβ expression in the renal cortex and medulla,9 whereas ovx in salt resistant (DR) rats caused decreases in cortical and increases in medullary ERα, and increases in ERβ. In addition, estradiol replacement returned ERβ expression to preovx levels in both DS and DR, but had no effect on ERα. In contrast, in internal mammary arteries from humans, ERβ mRNA expression was 10-fold higher than ERα or GPR30, and 17β-estradiol downregulated ERα, ERβ, and GPR30.10

Estradiol is usually thought to be renoprotective. For example, in cultured mesangial cells, 17β-estradiol inhibits apoptosis and transforming growth factor (TGF)-β activity and expression.11 In addition, estradiol is antiinflammatory.12–14 However, with low nitric oxide (NO) and high angiotensin (Ang) II, estradiol exacerbated renal injury via upregulation of renal AT1 receptor expression.15 In addition, in women, oral contraceptives increase in BP and albumin excretion,16 and occasionally result in hypertension17 and biopsy-proven renal damage in the absence of primary renal disease.18

The roles of the ER subtypes in renal function or injury have been studied mainly by using ERα and ERβ knockout (KO) mice. ERα is mainly responsible for gene regulation because 10 000 genes were upregulated in kidneys of wild-type (WT) and βERKO mice with estradiol.19 βERKO mice become hypertensive with aging, and males have higher BP,20 but both male and female are resistant to age-related glomerular sclerosis, suggesting that renal injury/disease does mediate the hypertension. αERKO males are also resistant to age-related glomerular sclerosis, but females exhibit both albuminuria and glomerular sclerosis. Ovx prevents glomerulosclerosis in female αERKO, not attributable to the reduction in estradiol or progesterone but to reduction in testosterone.21 ERβ does provide protection in ischemia/reperfusion injury of hearts (eg, smaller infarct size) in αERKO females, but not males.22 However, streptozotocin-diabetic αERKO females developed higher TGFβ expression than WT,23 suggesting that ERβ may play a role in diabetic neprhopathy.

ERα and ERβ are present in endothelial cells and vascular smooth muscle cells, but the expression is gender- and vascular bed–dependent.6,7 Similarly, the effect of estradiol on vasodilation is dependent on the vascular bed studied. For example, estradiol-mediated vasodilation attributable to nitric oxide (NO), via endothelial NO synthase (eNOS), was absent in femoral and carotid arteries from both αERKO and βERKO mice.24 This is consistent with previous studies showing that basal eNOS activity was reduced in αERKO mice.25 In contrast, Al Zubair and colleagues reported that ERβ agonist caused greater relaxation of female rat mesenteric arteries than did ERα agonist.26 However, both agonists had similar vasodilator effects in males.

Progesterone and the Kidney

Progesterone receptors have been found mainly in distal tubule cells, although they are present in cortex and medulla of males and females.27 The role that progesterone plays in physiology and pathology of the kidney is not clear. Progesterone has a high affinity for the mineralocorticoid receptor (MR) and can act as an MR antagonist. In rats with DOCA-salt hypertension, mediated by the MR, progesterone alone, the combination of progesterone and estrogen, but not estrogen alone, attenuated renal damage and preproendothelin mRNA expression,28 suggesting that treatment with progesterone may have acted as an MR antagonist in this study. However, progesterone can be degraded in the kidney to metabolites that have lower affinity for the MR.29 In contrast, in ovx rats with 5/6 renal ablation, estradiol protected against proteinuria and glomerulsclerosis, but rats treated with estradiol+progesterone exhibited the same renal damage as vehicle-treated rats.30 In this case then progesterone promoted renal injury. In another study, early ovx caused a reduction in renal functional reserve and fractional proximal tubular fluid output in middle-aged rats (13 months) that was reversed with estradiol alone or estradiol and progesterone.31 Progesterone may also increase sodium reabsorption independent of its effect on the MR, because progesterone alone moderately increased ENaC activity in cortical collecting duct cells, but progesterone and low-dose estradiol increased ENaC activity by 2-fold, whereas high-dose estradiol almost completely inhibited ENaC activity.32 Testosterone has also been shown to increase ENaC expression in the kidney,33 and progesterone can transactivate the androgen receptor.34 Furthermore, progesterone can be metabolized to both testosterone and dihydrotestosterone in the kidney.35 Therefore, some of the effects of progesterone on the kidney may be attributable to its androgenic effects.

Testosterone and the Kidney

The kidney can synthesize testosterone and dihydrotestosterone because it contains the cytochrome P450 enzymes that are necessary.35 Similar to the estradiol receptors, the complete nephron localization for the androgen receptor (AR) has not been elucidated. Mesangial cells, glomeruli, proximal tubules, and cortical collecting ducts contain AR.21,36 Treatment of normotensive rats with dihydrotestosterone increases proximal sodium reabsorption, via an Ang II–mediated mechanism, and BP,37 but neither GFR nor AT1 receptor binding was affected. This is in contrast to acute infusion of testosterone that increases GFR and renal plasma flow and reduces renal vascular resistance (Reckelhoff, unpublished results, 1998). Therefore, androgens have both chronic and acute effects on the kidney.

Male rats experience a more rapid reduction in GFR and more renal injury with age than females.37–40 However, the reduction in GFR cannot be fully accounted for by the level of glomerular injury found in the kidneys, suggesting that aging is a state of renal vasoconstriction. For example, in male normotensive rats, aged 20 to 22 months, GFR was reduced by 50% compared to young males and yet only 20% of their glomeruli exhibited sclerosis.38 In aging male SHR, GFR was reduced by 30% and renal vascular resistance was increased 30%, whereas less than 5% cof glomeruli had sclerosis.39 Castration of aging SHR and Munich Wistar rats prevents reductions in GFR and glomerular injury.37,39 In addition, castration prevents the increase in renal vascular resistance. Castration of male rats with renal-wrap hypertension also attenuated the glomerular injury and proteinuria.41 When castrated rats or ovx females with renal-wrap hypertension were treated with dihydrotestosterone, glomerular injury was exacerbated.

Testosterone can mediate renal injury in females. Testosterone supplements increased expression of AR and TGF-β1 in glomeruli of ovx B6 mice,21 and AR antagonism protects against renal injury in female TGR(mREN2)27.42 The concept that androgens may also be harmful to kidneys of females is important because postmenopausal women may produce more androgens as they age.35

Plasma testosterone levels are decreased in most men with aging and other chronic diseases, such as CKD.43 Thus many investigators believe that renal disease is independent of androgens. However, because the kidney is capable of synthesizing androgens,35 it is not clear whether reductions in plasma testosterone reflect similar changes in renal testosterone.

Diabetes, Hyperlipidemia, and Sex Steroids

Before puberty, renal complications of diabetes (DM) are rare, but the incidence of renal disease in DM sharply increases after puberty.44 In a large clinical trial of 27 805 individuals with type 1 DM, male sex was an independent risk factor associated with the development of CKD.45 Other studies have also shown that the “female protective factor” is lost in the presence of diabetes,46 perhaps because of a decrease in plasma estradiol as found in female rats with streptozotocin-induced type 1 DM.47 17β-Estradiol replacement reversed renal fibrosis.48 Similarly, in hypertensive type II DM, postmenopausal women, 17β-estradiol replacement was also shown to be protective against renal disease.49

Metabolic syndrome, including insulin resistance, type II DM, and dyslipidemia, constitutes a major risk factor for developing CKD. In a recent study, a positive correlation between the number of components of metabolic syndrome and the incidence of CKD was found.50 Of interest, no gender difference in the incidence of CKD was reported, with women having the same incidence as men.50 In Zucker (fa/fa) rats, a model of type 2DM and hyperlipidemia, there are gender differences in vascular reactivity, where the males exhibit an impaired response to vasoconstrictors and to endothelial-mediated vasodilation.51 Males exhibited a paradoxical decrease in vascular resistance in response to thromboxane agonist and blunting of the response to Ang II. In addition, Zucker males exhibited a blunted vasodilatory response to acetylcholine and a blunted vasoconstrictor response to nitro-l-arginine methyl ester (l-NAME), inhibitor of NOS. Castration improved vascular responses.52 However, in aging Zucker rats, ESRD was found to be the major cause of mortality, and a gender difference was not observed (males: 91.1%, females: 93.3%).53 Although it is possible that a reduction in estradiol could have played a role in lack of protection in females, administration of estradiol to ovx Zucker rats impaired renal function further and led to profound glomerulosclerosis.54 These data suggest that in presence of metabolic syndrome, type II DM, or dyslipidemia, the effects of sex steroids on renal disease are unpredictable.

Hypertension and Sex Steroids

Hypertension is more prevalent and more severe in men than women.55 However, the sex difference in BP is lost after menopause. Sex differences in renal injury in humans follow the BP; ie, hypertensive men have a higher incidence of ESRD than women.2 The mechanisms are not clear, but changes in sex steroid–mediated differences in glomerular capillary pressure (PGC) may play a role. Glomerular hypertension is a key factor in the pathogenesis of progressive glomerulosclerosis and renal failure, independent of the initial insult.56,57 For example, in response to Ang II infusion, men and women exhibited similar increases in BP and decline in effective renal plasma flow (ERPF),58 whereas GFR was maintained only in men, resulting in an increase of filtration fraction (FF). In women, GFR declined in parallel with ERPF, and thus there was little increase in FF,58 which is an indication of PGC. Thus PGC in men likely increased more in response to Ang II than in women, which if sustained over time, would lead to greater glomerular injury in men.

Hypertension in animal models is associated with the renal injury, although the extent depends on the age, the model, and the experimental design. In the SHR, BP is higher in males, but renal injury only occurs with aging, but PGC is elevated in males by age 9 months, before any renal damage.59 Although BP increases in female SHR after cessation of estrous cycling to levels not different or even higher than males,60 females exhibit little glomerulosclerosis compared to males.61 Whether PGC is increased in aged female SHR has not been determined.

Whether and how sex steroids could affect PGC is not clear, however. Testosterone has been shown to have modulating effects on calcium channels. For example, chronic testosterone causes an increase in T type calcium currents.62 Alternatively, L-type calcium currents are blocked by testosterone.63 Feng and colleagues reported that both L- and T-type calcium channels are present in afferent and efferent arterioles.64 It is possible that androgens could modulate these calcium currents leading to preglomerular vasodilation leading to an increase in PGC. Alternatively, estradiol could have the opposite effect on calcium channels and thus protect glomeruli from increased transmission of the systemic BP, protecting against increased PGC.

Sex Steroids and Renin-Angiotensin System

Inhibition of the renin-angiotensin system delays the progression of diabetic and nondiabetic renal diseases.65 Testosterone increases proximal sodium reabsorption via Ang II–mediated mechanisms37 and increases intrarenal angiotensinogen expression.66,67 If renin does not work at its Vmax, as in humans and rats, an increase in renin substrate would cause an increase in Ang II production. Testosterone could promote renal injury by a hemodynamic mechanism in which it stimulates Ang II production, leading to increases in sodium reabsorption in the proximal tubule with a concomitant reduction of sodium reaching the macula densa, resulting in a decrease in glomerular afferent resistance (compared to females) allowing greater transmission of systemic BP to the glomerular capillary.

Estrogen may protect against renal injury via its effects on components of the renin-angiotensin system. Estrogen reduces the number of AT1 receptors in many tissues, including the kidney, and attenuates tissue responsiveness to Ang II.68–71 Estrogen increases angiotensinogen levels, mainly in the liver,71 but appears to decrease plasma renin activity. However, the lack of protection from primary cardiovascular events with estrogen replacement found in the Women’s Health Initiative (WHI) study72 suggests that changes in the estrogen responsiveness occur after menopause. Whether the changes in estrogen responsiveness with age are attributable to changes in expression/intracellular signaling/transcription activation of the ERs or other mechanisms remain to be determined.

Sex Steroids and Endothelin

There is a paucity of studies regarding the interaction among sex hormones, the endothelin system, and renal disease. In female-to-male transsexuals, testosterone treatment increases plasma endothelin levels.73 In DOCA-salt rats, renal injury associated with ovx in females is ameliorated by endothelin (ETA) receptor antagonism.28 After warm ischemia, the early recovery of renal blood flow is delayed in male rats compared to females, due to a greater increase in renal vascular resistance in males, likely mediated in part by increased endothelin, because preproendothelin mRNA was elevated in kidneys of males but not females.74 In uninephrectomized spontaneously hypertensive-stroke prone rats (SHRsp), ovx females exhibited significantly greater glomerular damage and greater endothelin expression than estradiol-treated animals.75

Ang II has been shown to increase expression of preproendothelin in the kidney.76 Because androgens increase angiotensinogen and plasma renin activity, it is possible that androgens could increase Ang II leading to increased endothelin and subsequent renal injury. Alternatively, because estradiol can downregulate AT1 receptor expression, estrogen should prevent the increase in endothelin and protect against renal injury. This hypothesis remains to be tested.

Sex Steroids and Oxidative Stress

Growing evidence links oxidative stress and renal disease, including drug-induced nephrotoxicity,77,78 IgA nephropathy,79 ischemia-reperfusion injury,80 and diabetic nephropathy.81 Men with these diseases exhibit more renal injury than women.2 Estradiol is an antioxidant, and ovx increases renal NADPH oxidase activity and glomerulosclerosis index in female renal-wrap hypertensive rats; estradiol replacement abrogated these changes.82 Ovx also worsens adriamycin-induced nephropathy and augments oxidative stress, which was prevented by estradiol.78 Androgens are thought to increase oxidative stress. In humans, men have higher levels of indicators of oxidative stress than age-matched, premenopausal women.83 However, postmenopausal women have higher levels of oxidative stress than do their premenopausal counterparts.84 Few studies have examined sex differences in renal injury and the role of oxidative stress. BP in male SHR is reduced with antioxidants, such as tempol or apocynin, but not in females.85 Sullivan and colleagues reported that the activities of superoxide dismutase and catalase were augmented in kidneys from male SHR compared to females.86 Renal antioxidant enzyme expression is higher in male SHR than in females.85 However, unlike in male WKY rats, male SHR fail to upregulate renal expression of antioxidant enzymes when oxidative stress is increased with molsidomine.85 Whether oxidative stress is higher in male or female SHR is dependent on the tissue and on the age of the animals. In kidneys, oxidative stress, measured as increases in F2-isoprostane or lucigenin chemiluminescence, is slightly lower or similar in females and males.85 However, we have not examined whether renal damage in aging male SHR is ameliorated with chronic antioxidants, although BP is reduced, and therefore renal injury is also likely lessened. Whether in humans antioxidant therapy can attenuate or prevent CKD is unclear at the present.

Perspectives

The role that sex steroids play in CKD and in the progression to ESRD in humans is not clear. Sex steroids may not be causative of CKD in humans but are likely to be permissive of or protective against progression to ESRD. The mechanisms by which sex steroids could modulate renal disease are many, but in the Table, some of the possible mechanisms and how the sex steroids could affect these mechanisms are shown. Estradiol is mainly antioxidant, vasodilatory, and Ang II action-“inhibitory,” although not overtly so. The effect of estradiol on renal endothelin is not clear. Progesterone has been less well studied, but it is likely to be vasoconstricting chronically, antioxidant, antinatriuretic. The effect of progesterone on Ang II, AT1 receptor, and endothelin is not clear. Androgens, testosterone, and dihydrotestosterone are chronically vasoconstricting, prooxidant, antinatriuretic, and Ang II and endothelin-action stimulatory. Discovery of the mechanisms by which sex steroids impact CKD in humans will allow improvement of treatment paradigms that could be made specific if the patient is male or female. The role played by sex steroids in renal disease remains an exciting area for research in humans or animals.

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Table. How Sex Steroids May Modulate Renal Injury

Acknowledgments

Sources of Funding

J.C. Sartori-Valinotti and L.L. Yanes are recipients of American Heart Association, Southeast Affiliate, Postdoctoral Fellowships (#725561B and 0425461B, respectively). This work was supported by HL51971, HL69194, and HL66072 from the National Institutes of Health. L.L.Y. has received an AHA grant >$10 000; J.C.S.-V. has received an AHA grant >$10 000; J.F.R. has received 3 grants >$10 000 each.

Disclosures

None.

Footnotes

  • This paper was sent to Richard J. Roman, associate editor, for review by expert referees, editorial decision, and final disposition.

  • Received December 3, 2007.
  • Revision received December 28, 2007.
  • Accepted January 9, 2008.

References

  1. ↵
    Seliger SL, Davis C, Stehman-Breen C. Gender and the progression of renal disease. Curr Opin Nephrol Hypertens. 2001; 10: 219–225.
    OpenUrlPubMed
  2. ↵
    Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol. 2000; 11: 319–329.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Ishikawa I, Maeda K, Nakai S, Kawaguchi Y. Gender difference in the mean age at the induction of hemodialysis in patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2000; 35: 1072–1075.
    OpenUrlPubMed
  4. ↵
    Neugarten J, Gallo G, Silbiger S, Kasiske B. Glomerulosclerosis in aging humans is not influenced by gender. Am J Kidney Dis. 1999; 34: 884–888.
    OpenUrlPubMed
  5. ↵
    Potier M, Elliot SJ, Tack I, Lenz O, Striker GE, Striker LJ, Karl M. Expression and regulation of estrogen receptors in mesangial cells: influence on matrix metalloproteinase-9. J Am Soc Nephrol. 2001; 12: 241–251.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    Hodges YK, Tung L, Yan XD, Graham JD, Horwitz KB, Horwitz LD. Estrogen receptors alpha and beta: prevalence of estrogen receptor beta mRNA in human vascular smooth muscle and transcriptional effects. Circulation. 2000; 101: 1792–1798.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    Andersson C, Lydrup ML, Fernö M, Idvall I, Gustafsson J, Nilsson BO. Immunocytochemical demonstration of oestrogen receptor beta in blood vessels of the female rat. J Endocrinol. 2001; 169: 241–247.
    OpenUrlAbstract
  8. ↵
    Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol. 2006; 20: 1996–2009.
    OpenUrlCrossRefPubMed
  9. ↵
    Esqueda ME, Craig T, Hinojosa-Laborde C. Effect of ovariectomy on renal estrogen receptor alpha and estrogen receptor beta in young salt-sensitive and -resistant rats. Hypertension. 2007; 50: L768–L772.
    OpenUrlCrossRef
  10. ↵
    Haas E, Meyer MR, Schurr U, Bhattacharya I, Minotti R, Nguyen HH, Heigl A, Lachat M, Genoni M, Barton M. Differential effects of 17β-estradiol on function and expression of estrogen receptor alpha, estrogen receptor beta, and GPR30 in arteries and veins of patients with atherosclerosis. Hypertension. 2007; 49: 1358–1363.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    Negulescu O, Bognar I, Lei J, Devarajan P, Silbiger S, Neugarten J. Estradiol reverses TGF-beta1-induced mesangial cell apoptosis by a casein kinase 2-dependent mechanism. Kidney Int. 2002; 62: 1989–1998.
    OpenUrlCrossRefPubMed
  12. ↵
    Alvarez A, Hermenegildo C, Issekutz AC, Esplugues JV, Sanz MJ. Estrogens inhibit angiotensin II-induced leukocyte-endothelial cell interactions in vivo via rapid endothelial nitric oxide synthase and cyclooxygenase activation. Circ Res. 2002; 91: 1142–1150.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    Mori M, Tsukahara F, Yoshioka T, Irie K, Ohta H. Suppression by 17beta-estradiol of monocyte adhesion to vascular endothelial cells is mediated by estrogen receptors. Life Sci. 2004; 75: 599–609.
    OpenUrlCrossRefPubMed
  14. ↵
    Rodriguez E, Lopez R, Paez A, Masso F, Montano LF. 17Beta-estradiol inhibits the adhesion of leukocytes in tumornecrosisfactor (TNF)-alpha stimulated human endothelial cells by blocking interleukin (IL)-8 and MCP-1 secretion, but not its transcription. Life Sci. 2002; 71: 2181–2193.
    OpenUrlCrossRefPubMed
  15. ↵
    Oestreicher EM, Guo C, Seely EW, Kikuchi T, Martinez-Vasquez D, Jonasson L, Yao T, Burr D, Mayoral S, Roubsanthisuk W, Ricchiuti V, Adler GK. Estradiol increases proteinuria and angiotensin II type 1 receptor in kidneys of rats receiving L-NAME and angiotensin II. Kidney Int. 2006; 70: 1759–1768.
    OpenUrlCrossRefPubMed
  16. ↵
    Ribstein J, Halimi JM, du Cailar G, Mimran A. Renal characteristics and effect of angiotensin suppression in oral contraceptive users. Hypertension. 1999; 33: 90–95.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    Lim KG, Isles CG, Hodsman plateletglycoprotein (GP), Lever AF, Robertson JW. Malignant hypertension in women of childbearing age and its relation to the contraceptive pill. BMJ. 1987; 294: 1057–1059.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Boyd WN, Burden RP, Aber GM. 1975 Intrarenal vascular changes in patients receiving oestrogen-containing compounds–a clinical, histological and angiographic study. Quart J Med. 1975; 44: 415–431.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    Jelinsky SA, Harris HA, Brown EL, Flanagan K, Zhang X, Tunkey C, Lai K, Lane MV, Simcoe DK, Evans MJ. Global transcription profiling of estrogen activity: estrrogen receptor alpha regulates gene expression in the kidney. Endocrinol. 2003; 144: 701–710.
    OpenUrlCrossRefPubMed
  20. ↵
    Zhu Y, Bian Z, Lu P, Karas RH, Bao L, Cox D, Hodgin J, Shaul PW, Thoren P, Smithies O, Gustafsson JA, Mendelsohn ME. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science. 2002; 295: 505–508.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    Elliot SJ, Berho M, Korach K, Doublier S, Lupia E, Striker GE, Karl M. Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis. Kidney Int. 2007; 72: 464–472.
    OpenUrlCrossRefPubMed
  22. ↵
    Harris H. Estrogen receptor-β: Recent lessons from in vivo studies. Mol Endocrinol. 2007; 21: 1–13.
    OpenUrlCrossRefPubMed
  23. ↵
    Sun J, Langer WJ, Devish K, Lane PH. 2006 Compensatory kidney growth in estrogen receptor-alpha null mice. Am J Physio Renal Physiol. 2006; 290: F319–F323.
    OpenUrlCrossRef
  24. ↵
    Guo X, Razandi M, Pedram A, Kassab G, Levin ER. Estrogen induces vascular wall dilation: mediation through kinase signaling to nitric oxide and estrogen receptors alpha an beta. J Biol Chem. 2005; 280: 19704–19710.
    OpenUrlAbstract/FREE Full Text
  25. ↵
    Rubanyi GM, Freay AD, Kauser K, Sukovich D, Burton G, Lubahn DB, Couse JF, Curtis SW, Korach KS. Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption. J Clin Invest. 1997; 99: 2429–2437.
    OpenUrlCrossRefPubMed
  26. ↵
    Al Zubair K, Razak A, Bexis S, Docherty JR. Relaxations to oestrogen receptor subtype selective agonists in rat and mouse arteries. Eur J Pharmacol. 2005; 513: 101–108.
    OpenUrlCrossRefPubMed
  27. ↵
    Quinkler M, Diederich S, Bahr V, Oelkers W. The role of progesterone metabolism and androgen synthesis in renal blood pressure regulation. Horm Metab Res. 2004; 36: 381–386.
    OpenUrlCrossRefPubMed
  28. ↵
    Montezano AC, Callera GE, Mota AL, Fortes ZB, Nigro D, Carvalho MH, Zorn TM, Tostes RC. Endothelin contributes to the sexual differences in renal damage in DOCA-salt rats. Peptides. 2005; 26: 1454–1462.
    OpenUrlCrossRefPubMed
  29. ↵
    Bumke-Vogt C, Bahr V, Diderich S, Herrmann SM, Anagnostopoulos I, Oelkers W, Quinkler M. Expression of the progesterone receptor and progesterone-metabolising enzymes in the female and male human kidney. J Endocrinol. 2002; 175: 349–364.
    OpenUrlAbstract
  30. ↵
    Antus B, Zollosi Z, Mucsi I, Nemes Z, Rosivall L. Estradiol is nephroprotective in the rat remnant kidney. Nephrol Dial Transplant. 2003; 18: 54–61.
    OpenUrlAbstract/FREE Full Text
  31. ↵
    Nielsen CB, Flyvbjerg A, Bruun JM, Forman A, Wogensen L, Thomsen K. Decreases in renal functional reserve and proximal tubular fluid output in conscious oophorectomized rats: normalization with sex hormone substitution. J Am Soc Nephrol. 2003; 14: 3102–3110.
    OpenUrlAbstract/FREE Full Text
  32. ↵
    Chang CT, Sun CY, Pong CY Chen YC, Lin GP, Chang TC, Wu MS. Interaction of estrogen and progesterone in the regulation of sodium channels in collecting tubular cells. Chang Gung Med J. 2007; 30: 305–312.
    OpenUrlPubMed
  33. ↵
    Quinkler M, Bujalska IJ, Kaur K, Onyimba CU, Buhner S, Allolio B, Hughes SV, Hewison M, Stewart PM. Androgen receptor-mediated regulation of the alpha-subunit of the epithelial sodium channel in human kidney. Hypertension. 2005; 46: 787–798.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    Beck V, Reiter E, Jungbauer A Androgen receptor transactivation assay using green fluorescent protein as a reporter. Anal Biochem. In press.
  35. ↵
    Quinkler M, Bumke-Vogt C, Meyer B, Bahr V, Oelkers W, Diederich S. The human kidney is a progesterone-metabolizing and androgen-producing organ. The J Clin Endocrinol Metab. 2003; 88: 2803–2809.
    OpenUrlCrossRef
  36. ↵
    Quan A, Chakravarty S, Chen JK, Chen JC, Loleh S, Saini N, Harris RC, Capdevila J, Quigley R. Androgens augment proximal tubule transport. Am J Physiol Renal Physiol. 2004; 287: F452–F459.
    OpenUrlAbstract/FREE Full Text
  37. ↵
    Baylis C. Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor. J Clin Invest. 1994; 94: 1823–1829.
    OpenUrlCrossRefPubMed
  38. ↵
    Reckelhoff JF, Samsell L, Dey R, Racusen L, Baylis C. The effect of aging on glomerular hemodynamics in the rat. Am J Kidney Dis. 1992; 20: 70–75.
    OpenUrlPubMed
  39. ↵
    Fortepiani LA, Yanes L, Zhang H, Racusen LC, Reckelhoff JF. Role of androgens in mediating renal injury in aging SHR. Hypertension. 2003; 42: 952–955.
    OpenUrlAbstract/FREE Full Text
  40. ↵
    Hinojosa-Laborde C, Craig T, Zheng W, Ji H, Haywood JR, Sandberg K. Ovariectomy augments hypertension in aging female Dahl salt-sensitive rats. Hypertension. 2004; 44: 405–409.
    OpenUrlAbstract/FREE Full Text
  41. ↵
    Ji H, Menini S, Mok K, Zheng W, Pesce C, Kim J, Mulroney S, Sandberg K. Gonadal steroid regulation of renal injury in renal wrap hypertension. Am J Physiol Renal Physiol. 2005; 288: F513–F520.
    OpenUrlAbstract/FREE Full Text
  42. ↵
    Baltatu O, Cayla C, Iliescu R, Andreev D, Bader M. Abolition of end-organ damage by antiandrogen treatment in female hypertensive transgenic rats. Hypertension. 2003; 41: 830–833.
    OpenUrlAbstract/FREE Full Text
  43. ↵
    Holdsworth S, Atkins RC, de Kretser DM. The pituitary-testicular axis in men with chronic renal failure. N Engl J Med. 1977; 296: 1245–1249.
    OpenUrlPubMed
  44. ↵
    Lane PH. 2002 Diabetic kidney disease: impact of puberty. Am J Physiol Renal Physiol. 2002; 283: F589–F600.
    OpenUrlAbstract/FREE Full Text
  45. ↵
    Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P, Holl RW. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diab Care. 2007; 30: 2523–2528.
    OpenUrlAbstract/FREE Full Text
  46. ↵
    Breyer JA, Bain RP, Evans JK, Nahman NS Jr, Lewis EJ, Cooper M, McGill J, Berl T. Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. Kidney Int. 1996; 50: 1651–1658.
    OpenUrlCrossRefPubMed
  47. ↵
    Wells CC, Riazi S, Mankhey RW, Bhatti F, Ecelbarger C, Maric C. Diabetic nephropathy is associated with decreased circulating estradiol levels and imbalance in the expression of renal estrogen receptors. Gend Med. 2005; 2: 227–237.
    OpenUrlCrossRefPubMed
  48. ↵
    Dixon A, Maric C. 17beta-Estradiol attenuates diabetic kidney disease by regulating extracellular matrix and transforming growth factor-beta protein expression and signaling. Am J Physiol Renal Physiol. 2007; 293: F1678–F1690.
    OpenUrlAbstract/FREE Full Text
  49. ↵
    Szekacs B, Vajo Z, Varbiro S, Kakucs R, Vaslaki L, Acs N, Mucsi I, Brinton EA. Postmenopausal hormone replacement improves proteinuria and impaired creatinine clearance in type 2 diabetes mellitus and hypertension. BJOG. 2000; 107: 1017–1021.
    OpenUrlPubMed
  50. ↵
    Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Int Med. 2004; 140: 167–174.
    OpenUrlCrossRefPubMed
  51. ↵
    Ajayi AA, Hercule H, Cory J, Hayes BE, Oyekan AO. Gender difference in vascular and platelet reactivity to thromboxane A(2)-mimetic U46619 and to endothelial dependent vasodilation in Zucker fatty (hypertensive, hyperinsulinemic) diabetic rats. Diab Res Clin Prac. 2003; 59: 11–24.
    OpenUrlCrossRef
  52. ↵
    Ajayi AA, Ogungbade GO, Okorodudu AO. Sex hormone regulation of systemic endothelial and renal microvascular reactivity in type-2 diabetes: studies in gonadectomized and sham-operated Zucker diabetic rats. Eur J Clin Invest. 2004; 34: 349–357.
    OpenUrlCrossRefPubMed
  53. ↵
    Johnson PR, Stern JS, Horwitz BA, Harris RE Jr, Greene SF. Longevity in obese and lean male and female rats of the Zucker strain: prevention of hyperphagia. Am J Clin Nutr. 1997; 66: 890–903.
    OpenUrlAbstract/FREE Full Text
  54. ↵
    Stevenson FT, Wheeldon CM, Gades MD, Kaysen GA, Stern JS, van Goor H. Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat. Kidney Intl. 2000; 57: 1927–1935.
    OpenUrlCrossRefPubMed
  55. ↵
    Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, Horan MJ, Labarthe D. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995; 25: 305–313.
    OpenUrlAbstract/FREE Full Text
  56. ↵
    Dworkin LD, Feiner HD. Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension. J Clin Invest. 1986; 77: 797–809.
    OpenUrlPubMed
  57. ↵
    Hostetter TH, Rennke HG, Brenner BM. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982; 72: 375–380.
    OpenUrlCrossRefPubMed
  58. ↵
    Miller JA, Anacta LA, Cattran DC. Impact of gender on the renal response to angiotensin II. Kidney Intl. 1999; 55: 278–285.
    OpenUrlCrossRefPubMed
  59. ↵
    Tolbert EM, Weisstuch J, Feiner HD, Dworkin LD. Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat. Am J Physiol Renal Physiol. 2000; 278: F839–F846.
    OpenUrlAbstract/FREE Full Text
  60. ↵
    Reckelhoff JF, Fortepiani LA. Novel mechanisms responsible for postmenopausal hypertension. Hypertension. 2004; 43: 918–923.
    OpenUrlAbstract/FREE Full Text
  61. ↵
    Komatsu K, Frohlich ED, Ono H, Ono Y, Numabe A, Willis GW. Glomerular dynamics and morphology of aged spontaneously hypertensive rats. Effects of angiotensin-converting enzyme inhibition. Hypertension. 1995; 25: 207–213.
    OpenUrlAbstract/FREE Full Text
  62. ↵
    Michels G, Er F, Eicks M, Herzig S, Hoppe UC. Long-term and immediate effect of testosterone on single T-type calcium channel in neonatal rat cardiomyocytes. Endocrinol. 2006; 147: 5160–5169.
    OpenUrlCrossRefPubMed
  63. ↵
    Scragg JL, Jones RD, Channer KS, Jones TH, Peers C. Testosterone is a potent inhibitor of L-type Ca(2+) channels. Biochem Biophys Res Comm. 2004; 318: 503–506.
    OpenUrlCrossRefPubMed
  64. ↵
    Feng MG, Li M, Navar LG. T-type calcium channels in the regulation of afferent and efferent arterioles in rats. Am J Physiol Renal Physiol. 2004; 286: F331–F337.
    OpenUrlAbstract/FREE Full Text
  65. ↵
    Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int. 2005; 67: 799–812.
    OpenUrlCrossRefPubMed
  66. ↵
    Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992; 19: 456–463.
    OpenUrlAbstract/FREE Full Text
  67. ↵
    Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989; 83: 1941–1945.
    OpenUrlCrossRefPubMed
  68. ↵
    Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, Stablein A, Beckers F, Smits JF, Daemen MJ, Vetter H, Bohm M. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circ. 1998; 97: 2197–2201.
    OpenUrlAbstract/FREE Full Text
  69. ↵
    Owonikoko TK, Fabucci ME, Brown PR, Nisar N, Hilton J, Mathews WB, Ravert HT, Rauseo P, Sandberg K, Dannals RF, Szabo Z. In vivo investigation of estrogen regulation of adrenal and renal angiotensin (AT1) receptor expression by PET. J Nucl Med. 1994; 45: 94–100.
    OpenUrl
  70. ↵
    Rogers JL, Mitchell AR, Maric C, Sandberg K, Myers A, Mulroney SE. Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R794–R799.
    OpenUrlAbstract/FREE Full Text
  71. ↵
    Klett C, Hellmann W, Hackenthal E, Ganten D. Modulation of tissue angiotensinogen gene expression by glucocorticoids, estrogens, and androgens in SHR and WKY rats. Clin Exp Hypertens. 1993; 15: 683–708.
    OpenUrlCrossRefPubMed
  72. ↵
    Hsia J, Langer RD, Manson JE, Kuller L, Johnson KC, Hendrix SL, Pettinger M, Heckbert SR, Greep N, Crawford S, Eaton CB, Kostis JB, Caralis P, Prentice R. Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative. Arch Int Med. 2006; 166: 357–365.
    OpenUrlCrossRefPubMed
  73. ↵
    van Kesteren PJ, Kooistra T, Lansink M, van Kamp GJ, Asscheman H, Gooren LJ, Emeis JJ, Vischer UM, Stehouwer CD. The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning. Thromb Haem. 1998; 79: 1029–1033.
    OpenUrlPubMed
  74. ↵
    Muller V, Losonczy G, Heemann U, Vannay A, Fekete A, Reusz G, Tulassay T, Szabo AJ. Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin. Kidney Int. 2002; 62: 1364–1371.
    OpenUrlCrossRefPubMed
  75. ↵
    Gross ML, Adamczak M, Rabe T, Harbi NA, Krtil J, Koch A, Hamar P, Amann K, Ritz E. Beneficial effects of estrogens on indices of renal damage in uninephrectomized SHRsp rats. J Am Soc Nephrol. 2004; 15: 348–358.
    OpenUrlAbstract/FREE Full Text
  76. ↵
    Alexander BT, Cockrell KL, Rinewalt AN, Herrington JN, Granger JP. Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension. Am J Physiol Regul Integr Comp Physiol. 2001; 280: R1388–R1392.
    OpenUrlAbstract/FREE Full Text
  77. ↵
    Cetin H, Olgar S, Oktem F, Ciris M, Uz E, Aslan C, Ozguner F. Novel evidence suggesting an anti-oxidant property for erythropoietin on vancomycin-induced nephrotoxicity in a rat model. Clin Exp Pharmacol Physiol. 2007; 34: 1181–1185.
    OpenUrlPubMed
  78. ↵
    Montilla P, Tunez I, Munoz MC, Delgado MJ, Salcedo M. Hyperlipidemic nephropathy induced by adriamycin in ovariectomized rats: role of free radicals and effect of 17-beta-estradiol administration. Nephron. 2000; 85: 65–70.
    OpenUrlCrossRefPubMed
  79. ↵
    Ong-ajyooth L, Ong-ajyooth S, Parichatikanond P. The effect of alpha-tocopherol on the oxidative stress and antioxidants in idiopathic IgA nephropathy. J Med Assoc Thai. 2006; 89 Suppl 5: S164–S170.
    OpenUrlPubMed
  80. ↵
    Singh D, Chander V, Chopra K. Carvedilol attenuates ischemia-reperfusion-induced oxidative renal injury in rats. Fund Clin Pharmacol. 2004; 18: 627–634.
    OpenUrlCrossRefPubMed
  81. ↵
    Prabhakar S, Starnes J, Shi S, Lonis B, Tran R. Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J Am Soc Nephrol. 2007; 18: 2945–2952.
    OpenUrlAbstract/FREE Full Text
  82. ↵
    Ji H, Zheng W, Menini S, Pesce C, Kim J, Wu X, Mulroney SE, Sandberg K. Female protection in progressive renal disease is associated with estradiol attenuation of superoxide production. Gend Med. 2007; 4: 56–71.
    OpenUrlCrossRefPubMed
  83. ↵
    Ide T, Tsutsui H, Ohashi N, Hayashidani S, Suematsu N, Tsuchihashi M, Tamai H, Takeshita A. Greater oxidative stress in healthy young men compared with premenopausal women. Arterioscler Thromb Vasc Biol. 2002; 22: 438–442.
    OpenUrlAbstract/FREE Full Text
  84. ↵
    Helmersson J, Mattsson P, Basu S. Prostaglandin (PG) F(2alpha) metabolite and F2-isoprostane excretion in migraine. Clin Sci (Lond). 2002; 102: 39–43.
    OpenUrlPubMed
  85. ↵
    Sartori-Valinotti JC, Iliescu R, Fortepiani LA, Yanes LL, Reckelhoff JF. Sex differences in oxidative stress and the impact on blood pressure control and cardiovascular disease. Clin Exp Pharmacol Physiol. 2007; 34: 938–945.
    OpenUrlCrossRefPubMed
  86. ↵
    Sullivan JC, Sasser JM, Pollock JS. Sexual dimorphism in oxidant status in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2007; 292: R764–R768.
    OpenUrlAbstract/FREE Full Text
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Hypertension
April 2008, Volume 51, Issue 4
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    • Estradiol and the Kidney
    • Progesterone and the Kidney
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    Sex Steroids and Renal Disease
    Licy L. Yanes, Julio C. Sartori-Valinotti and Jane F. Reckelhoff
    Hypertension. 2008;51:976-981, originally published March 19, 2008
    https://doi.org/10.1161/HYPERTENSIONAHA.107.105767

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    Sex Steroids and Renal Disease
    Licy L. Yanes, Julio C. Sartori-Valinotti and Jane F. Reckelhoff
    Hypertension. 2008;51:976-981, originally published March 19, 2008
    https://doi.org/10.1161/HYPERTENSIONAHA.107.105767
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