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Jørgen Frøkiær

Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α. / Cheema, Muhammad Umar; Irsik, Debra L; Wang, Yan; Miller-Little, William; Hyndman, Kelly A; Marks, Eileen S; Frøkiær, Jørgen; Boesen, Erika I; Nørregaard, Rikke.

In: American Journal of Physiology: Renal Physiology, Vol. 309, No. 4, 15.08.2015, p. F305-17.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Cheema, MU, Irsik, DL, Wang, Y, Miller-Little, W, Hyndman, KA, Marks, ES, Frøkiær, J, Boesen, EI & Nørregaard, R 2015, 'Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α', American Journal of Physiology: Renal Physiology, vol. 309, no. 4, pp. F305-17. https://doi.org/10.1152/ajprenal.00685.2014

APA

Cheema, M. U., Irsik, D. L., Wang, Y., Miller-Little, W., Hyndman, K. A., Marks, E. S., Frøkiær, J., Boesen, E. I., & Nørregaard, R. (2015). Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α. American Journal of Physiology: Renal Physiology, 309(4), F305-17. https://doi.org/10.1152/ajprenal.00685.2014

CBE

Cheema MU, Irsik DL, Wang Y, Miller-Little W, Hyndman KA, Marks ES, Frøkiær J, Boesen EI, Nørregaard R. 2015. Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α. American Journal of Physiology: Renal Physiology. 309(4):F305-17. https://doi.org/10.1152/ajprenal.00685.2014

MLA

Cheema, Muhammad Umar et al. "Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α". American Journal of Physiology: Renal Physiology. 2015, 309(4). F305-17. https://doi.org/10.1152/ajprenal.00685.2014

Vancouver

Cheema MU, Irsik DL, Wang Y, Miller-Little W, Hyndman KA, Marks ES et al. Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α. American Journal of Physiology: Renal Physiology. 2015 Aug 15;309(4):F305-17. https://doi.org/10.1152/ajprenal.00685.2014

Author

Cheema, Muhammad Umar ; Irsik, Debra L ; Wang, Yan ; Miller-Little, William ; Hyndman, Kelly A ; Marks, Eileen S ; Frøkiær, Jørgen ; Boesen, Erika I ; Nørregaard, Rikke. / Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α. In: American Journal of Physiology: Renal Physiology. 2015 ; Vol. 309, No. 4. pp. F305-17.

Bibtex

@article{2b1cb7290b9641b2a7e2d4f373ad3def,
title = "Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α",
abstract = "While there is evidence that sex hormones influence multiple systems involved in salt and water homeostasis, the question of whether sex hormones regulate aquaporin-2 (AQP2) and thus water handling by the collecting duct has been largely ignored. Accordingly, the present study investigated AQP2 expression, localization and renal water handling in intact and ovariectomized (OVX) female rats, with and without estradiol or progesterone replacement. OVX resulted in a significant increase in urine osmolality and increase in p256-AQP2 in the renal cortex at 7 days post-OVX, as well as induced body weight changes. Relative to OVX alone, estradiol repletion produced a significant increase in urine output, normalized urinary osmolality and reduced both total AQP2 (protein and mRNA) and p256-AQP2 expression, whereas progesterone repletion had little effect. Direct effects of estradiol on AQP2 mRNA and protein levels were further tested in vitro using the mpkCCD principal cell line. Estradiol treatment of mpkCCD cells reduced AQP2 at both the mRNA and protein level in the absence of deamino-8-d-AVP (dDAVP) and significantly blunted the dDAVP-induced increase in AQP2 at the protein level only. We determined that mpkCCD and native mouse collecting ducts express both estrogen receptor (ER)α and ERβ and that female mice lacking ERα displayed significant increases in AQP2 protein compared with wild-type littermates, implicating ERα in mediating the inhibitory effect of estradiol on AQP2 expression. These findings suggest that changes in estradiol levels, such as during menopause or following reproductive surgeries, may contribute to dysregulation of water homeostasis in women.",
keywords = "Animals, Aquaporin 2, Cell Line, Down-Regulation, Drinking, Eating, Estradiol, Estrogen Receptor alpha, Estrogen Replacement Therapy, Female, Kidney Tubules, Collecting, Mice, Inbred C57BL, Mice, Knockout, Osmolar Concentration, Osmoregulation, Ovariectomy, Phosphorylation, Progesterone, Protein Transport, RNA, Messenger, Rats, Wistar, Time Factors, Urination, Weight Gain, Journal Article, Research Support, Non-U.S. Gov't",
author = "Cheema, {Muhammad Umar} and Irsik, {Debra L} and Yan Wang and William Miller-Little and Hyndman, {Kelly A} and Marks, {Eileen S} and J{\o}rgen Fr{\o}ki{\ae}r and Boesen, {Erika I} and Rikke N{\o}rregaard",
note = "Copyright {\textcopyright} 2015 the American Physiological Society.",
year = "2015",
month = aug,
day = "15",
doi = "10.1152/ajprenal.00685.2014",
language = "English",
volume = "309",
pages = "F305--17",
journal = "American Journal of Physiology: Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4",

}

RIS

TY - JOUR

T1 - Estradiol regulates AQP2 expression in the collecting duct; a novel inhibitory role for estrogen receptor α

AU - Cheema, Muhammad Umar

AU - Irsik, Debra L

AU - Wang, Yan

AU - Miller-Little, William

AU - Hyndman, Kelly A

AU - Marks, Eileen S

AU - Frøkiær, Jørgen

AU - Boesen, Erika I

AU - Nørregaard, Rikke

N1 - Copyright © 2015 the American Physiological Society.

PY - 2015/8/15

Y1 - 2015/8/15

N2 - While there is evidence that sex hormones influence multiple systems involved in salt and water homeostasis, the question of whether sex hormones regulate aquaporin-2 (AQP2) and thus water handling by the collecting duct has been largely ignored. Accordingly, the present study investigated AQP2 expression, localization and renal water handling in intact and ovariectomized (OVX) female rats, with and without estradiol or progesterone replacement. OVX resulted in a significant increase in urine osmolality and increase in p256-AQP2 in the renal cortex at 7 days post-OVX, as well as induced body weight changes. Relative to OVX alone, estradiol repletion produced a significant increase in urine output, normalized urinary osmolality and reduced both total AQP2 (protein and mRNA) and p256-AQP2 expression, whereas progesterone repletion had little effect. Direct effects of estradiol on AQP2 mRNA and protein levels were further tested in vitro using the mpkCCD principal cell line. Estradiol treatment of mpkCCD cells reduced AQP2 at both the mRNA and protein level in the absence of deamino-8-d-AVP (dDAVP) and significantly blunted the dDAVP-induced increase in AQP2 at the protein level only. We determined that mpkCCD and native mouse collecting ducts express both estrogen receptor (ER)α and ERβ and that female mice lacking ERα displayed significant increases in AQP2 protein compared with wild-type littermates, implicating ERα in mediating the inhibitory effect of estradiol on AQP2 expression. These findings suggest that changes in estradiol levels, such as during menopause or following reproductive surgeries, may contribute to dysregulation of water homeostasis in women.

AB - While there is evidence that sex hormones influence multiple systems involved in salt and water homeostasis, the question of whether sex hormones regulate aquaporin-2 (AQP2) and thus water handling by the collecting duct has been largely ignored. Accordingly, the present study investigated AQP2 expression, localization and renal water handling in intact and ovariectomized (OVX) female rats, with and without estradiol or progesterone replacement. OVX resulted in a significant increase in urine osmolality and increase in p256-AQP2 in the renal cortex at 7 days post-OVX, as well as induced body weight changes. Relative to OVX alone, estradiol repletion produced a significant increase in urine output, normalized urinary osmolality and reduced both total AQP2 (protein and mRNA) and p256-AQP2 expression, whereas progesterone repletion had little effect. Direct effects of estradiol on AQP2 mRNA and protein levels were further tested in vitro using the mpkCCD principal cell line. Estradiol treatment of mpkCCD cells reduced AQP2 at both the mRNA and protein level in the absence of deamino-8-d-AVP (dDAVP) and significantly blunted the dDAVP-induced increase in AQP2 at the protein level only. We determined that mpkCCD and native mouse collecting ducts express both estrogen receptor (ER)α and ERβ and that female mice lacking ERα displayed significant increases in AQP2 protein compared with wild-type littermates, implicating ERα in mediating the inhibitory effect of estradiol on AQP2 expression. These findings suggest that changes in estradiol levels, such as during menopause or following reproductive surgeries, may contribute to dysregulation of water homeostasis in women.

KW - Animals

KW - Aquaporin 2

KW - Cell Line

KW - Down-Regulation

KW - Drinking

KW - Eating

KW - Estradiol

KW - Estrogen Receptor alpha

KW - Estrogen Replacement Therapy

KW - Female

KW - Kidney Tubules, Collecting

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Osmolar Concentration

KW - Osmoregulation

KW - Ovariectomy

KW - Phosphorylation

KW - Progesterone

KW - Protein Transport

KW - RNA, Messenger

KW - Rats, Wistar

KW - Time Factors

KW - Urination

KW - Weight Gain

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1152/ajprenal.00685.2014

DO - 10.1152/ajprenal.00685.2014

M3 - Journal article

C2 - 26062878

VL - 309

SP - F305-17

JO - American Journal of Physiology: Renal Physiology

JF - American Journal of Physiology: Renal Physiology

SN - 1931-857X

IS - 4

ER -