title: Androgens drive divergent responses to salt stress in male versus female rat kidneys.
abstract: 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.
authors.affiliation: Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA. david_gerhold@merck.com
authors.forename: David
authors.initials: D
authors.lastname: Gerhold
authors.forename: Ansuman
authors.initials: A
authors.lastname: Bagchi
authors.forename: Meiqing
authors.initials: M
authors.lastname: Lu
authors.forename: David
authors.initials: D
authors.lastname: Figueroa
authors.forename: Kevin
authors.initials: K
authors.lastname: Keenan
authors.forename: Dan
authors.initials: D
authors.lastname: Holder
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Brett
authors.initials: B
authors.lastname: Connolly
authors.forename: Christopher
authors.initials: C
authors.lastname: Austin
authors.forename: Magdalena
authors.initials: M
authors.lastname: Alonso-Galicia
mesh_terms: 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
chemical_list: D000728:Androgens; D015777:Eicosanoids; D017673:Sodium Chloride, Dietary