Androgens drive divergent responses to salt stress in male versus female rat kidneys.
Dahl-Iwai (DI) salt-sensitive rats were studied using microarrays to identify sex-specific differences in the kidney, both basal differences and differences in responses to a high-salt diet. In DI rat kidneys, gene expression profiles demonstrated inflammatory and fibrotic responses selectively in females. Gonadectomy of DI rats abrogated sex differences in gene expression. Gonadectomized female and gonadectomized male DI rats both responded to high salt with the same spectrum of gene expression changes as intact female DI rats. Androgens dominated the sex-selective responses to salt. Several androgen-responsive genes with roles potentiating the differential responses to salt were identified, including increased male expression of angiotensin-vasopressin receptor and prolactin receptor, decreased 5 alpha-reductase, and mixed increases and decreases in expression of Cyp4a genes that can produce eicosanoid hormones. These sex differences potentiate sodium retention by males and increase kidney function during gestation in females.
Gerhold
David
D
Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA. david_gerhold@merck.com
Bagchi
Ansuman
A
Lu
Meiqing
M
Figueroa
David
D
Keenan
Kevin
K
Holder
Dan
D
Wang
Yuhong
Y
Jin
Hong
H
Connolly
Brett
B
Austin
Christopher
C
Alonso-Galicia
Magdalena
M
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D015777:Eicosanoids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005802:Genes, MHC Class II; D006977:Hypertension, Renal / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D020303:Rats, Inbred Dahl; D012727:Sex Characteristics; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity*; D013312:Stress, Physiological / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D000728:Androgens; D015777:Eicosanoids; D017673:Sodium Chloride, Dietary