Journal article
Testosterone regulation of renal cystathionine beta-synthase: implications for sex-dependent differences in plasma homocysteine levels
American journal of physiology. Renal physiology, Vol.293(2), pp.F594-600
08/2007
DOI: 10.1152/ajprenal.00171.2007
PMID: 17537983
Abstract
Elevated plasma total homocysteine (tHcy) is an independent risk factor for ischemic heart disease and stroke. Epidemiological studies reveal that men have higher tHcy levels than women, but the mechanism underlying this sex-dependent difference is unknown. One route for intracellular disposal of homocysteine is catalyzed by cystathionine beta-synthase (CBS). Renal function is known to be an important determinant of tHcy, and, in this study, we demonstrate that renal CBS expression and activity in mice diminished approximately twofold after castration, whereas ovariectomization was without effect. The higher renal CBS activity in males (22.7 +/- 3.1 mmol cystathionine.h(-1).kg kidney(-1)) vs. females (8.4 +/- 3.4 mmol cystathionine.h(-1).kg kidney(-1), P < or = 10(-6)) in C57Bl/6J mice was associated with lower plasma tHcy levels in males vs. females, and this difference was exacerbated in Cbs+/- mice (7.7 +/- 1.9 micromol/l in males vs. 13.8 +/- 6.4 micromol/l in females, P = 0.005). Surprisingly, mammals exhibit a diversity of regulatory patterns for kidney CBS, with females exhibiting lower CBS activity in mice, higher in rats and humans, and being indistinguishable from males in rabbit, hamster, and guinea pig. Our data suggest that testosterone-dependent regulation of human CBS in kidney may contribute to sex-dependent differences in homocysteine transsulfuration.
Details
- Title: Subtitle
- Testosterone regulation of renal cystathionine beta-synthase: implications for sex-dependent differences in plasma homocysteine levels
- Creators
- Victor Vitvitsky - Redox Biology Center and the Biochemistry Dept., University of Nebraska, Lincoln, NE 68588-0664, USAAnna PrudovaSally StablerSanjana DayalSteven R LentzRuma Banerjee
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.293(2), pp.F594-600
- Publisher
- United States
- DOI
- 10.1152/ajprenal.00171.2007
- PMID
- 17537983
- ISSN
- 1931-857X
- eISSN
- 1522-1466
- Grant note
- HL-63943 / NHLBI NIH HHS R01 HL063943 / NHLBI NIH HHS DK-64959 / NIDDK NIH HHS
- Language
- English
- Date published
- 08/2007
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984065392702771
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