Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice.
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.
Elliot
Sharon J
SJ
Vascular Biology Institute and Departments of Medicine and Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA.
Karl
Michael
M
Berho
Mariana
M
Potier
Mylene
M
Zheng
Feng
F
Leclercq
Baudouin
B
Striker
Gary E
GE
Striker
Liliane J
LJ
D000419:Albuminuria; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000652:urine; D018450:Disease Progression; D004198:Disease Susceptibility; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000517:prevention & control* / Q000652:urine; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D010052:Ovariectomy
D004967:Estrogens; D003404:Creatinine