Differential effects of 17beta-estradiol and of synthetic progestins on aldosterone-salt-induced kidney disease.
Elevated mineralocorticoid levels and female sex hormones have been shown to confer opposing effects on renal injury, but their combined effects are still unknown.


OBJECTIVE
Identify the function of estrogens and of different synthetic progestins on aldosterone salt-mediated renal disease.


METHODS
The role of 17beta-estradiol, medroxyprogesterone acetate (MPA), and drospirenone during renal injury was studied in Wistar rats subjected to uni-nephrectomy plus aldosterone salt treatment.


RESULTS
Aldo-salt treatment of intact, ovariectomized, and estradiol-treated female rats resulted in remnant kidney hypertrophy without structural damage. Co-treatment with MPA, but not with drospirenone, increased kidney hypertrophy, fluid turnover, sodium retention, and potassium excretion. Medroxyprogesterone acetate also caused glomerular, vascular, tubular, and interstitial lesions that were accompanied by increased blood pressure and enhanced NADPH oxidase (p67phox) and sodium channel (alpha-ENaC) expression. Drospirenone, a progestin with anti-mineralocorticoid function, and spironolactone prevented kidney hypertrophy, hypertension, and sodium retention. Drospirenone and spironolactone also increased renal angiotensin II type 2 receptor expression and relieved aldosterone-induced suppression of serum angiotensin II levels.


CONCLUSIONS
The choice of specific synthetic progestins has profound implications on the development of kidney injury and renal gene expression under conditions of elevated aldosterone serum levels and salt intake.
Department of Medicine, University of Würzburg, Germany.
Paula-Anahi
PA
Arias-Loza
Melanie
M
Muehlfelder
Susan A
SA
Elmore
Robert
R
Maronpot
Kai
K
Hu
Hartmut
H
Blode
Christa
C
Hegele-Hartung
Karl Heinrich
KH
Fritzemeier
Georg
G
Ertl
Theo
T
Pelzer
D000450:Aldosterone / Q000378:metabolism / Q000633:toxicity; D000736:Androstenes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D053503:Epithelial Sodium Channels / Q000378:metabolism; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D006984:Hypertrophy / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017258:Medroxyprogesterone Acetate / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D045167:Progesterone Congeners / Q000378:metabolism / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012965:Sodium Chloride / Q000633:toxicity; D013148:Spironolactone / Q000378:metabolism / Q000494:pharmacology
D000736:Androstenes; D053503:Epithelial Sodium Channels; D045167:Progesterone Congeners; D018809:Proliferating Cell Nuclear Antigen; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018160:Receptors, Cytoplasmic and Nuclear; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; C035144:drospirenone