Estrogen Deficiency Accelerates Progression of Glomerulosclerosis in Susceptible Mice
The American Journal of Pathology. 2003-05-01; 162(5): 1441-1448
DOI: 10.1016/s0002-9440(10)64277-0
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1. Am J Pathol. 2003 May;162(5):1441-8. doi: 10.1016/S0002-9440(10)64277-0.
Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible
mice.
Elliot SJ(1), Karl M, Berho M, Potier M, Zheng F, Leclercq B, Striker GE,
Striker LJ.
Author information:
(1)Vascular Biology Institute and Departments of Medicine and Surgery,
University of Miami School of Medicine, Miami, Florida 33136, USA.
Estrogen deficiency may contribute to the development and progression of
glomerulosclerosis in postmenopausal women. The responsiveness to estrogens
could be controlled by genetic traits related to those that determine the
susceptibility to glomerular scarring. This study was undertaken to determine
whether the intensity of the sclerotic response was modified by the estrogen
status in sclerosis-prone ROP Os/+ mice. Ovariectomized ROP Os/+ mice developed
more severe renal dysfunction and glomerulosclerosis than intact, ie, estrogen
sufficient age-matched female mice. Ovariectomized ROP Os/+ exhibited increased
accumulation of extracellular matrix, predominantly of laminin, and a marked
distortion of the glomerular architecture. We found an increase in macrophage
infiltration in the mesangium of ovariectomized ROP Os/+. Estrogen deficiency
decreased glomerular estrogen receptor expression in ROP Os/+ mice, which we had
previously found to be low in the parental ROP strain. Thus, although
physiological estrogen levels in young ROP Os/+ mice could not prevent the
development of glomerulosclerosis, estrogen deficiency accelerated the
progression of glomerular scarring in this mouse strain. This suggests that
estrogen replacement will slow but not prevent the progression of
glomerulosclerosis. It underscores the importance of the genetic composition of
individuals that determines the susceptibility to diseases as well as the
response to treatment.
DOI: 10.1016/S0002-9440(10)64277-0
PMCID: PMC1851210
PMID: 12707027 [Indexed for MEDLINE]