Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells.
BACKGROUND
The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells.


METHODS
Cultured human glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with progesterone, beta-estradiol or testosterone followed by determination of cytotoxicity.


RESULTS
Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, beta-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor) by any cell type at any time point.


CONCLUSIONS
These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.
Division of Nephrology, University of Utah Health Sciences Center and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA. alisa.highes@hsc.utah.edu
Alisa K
AK
Hughes
Douglas I
DI
Schmid
Donald E
DE
Kohan
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D022622:Shiga Toxin 1 / Q000633:toxicity*; D013739:Testosterone / Q000494:pharmacology; D018675:Toxicity Tests
D015295:Antigens, Tumor-Associated, Carbohydrate; C472766:Gb3 antigen; D012739:Gonadal Steroid Hormones; D022622:Shiga Toxin 1; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol