Androgen-dependent regulation of human angiotensinogen expression in KAP-hAGT transgenic mice. Am J Physiol Renal Physiol 2001 Jan;280(1):F54-60
Date
01/03/2001Pubmed ID
11133514DOI
10.1152/ajprenal.2001.280.1.F54Scopus ID
2-s2.0-0034997199 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
We previously reported a novel transgenic model expressing human angiotensinogen from the kidney androgen-regulated protein promoter, and demonstrated sexually dimorphic expression. Herein, we investigated the hormonal regulation of this transgene. Testosterone increased transgene expression in female mice in a dose- and time-dependent manner and was not detectable 3-days after treatment was halted. High doses of estrogen were required to induce the transgene. Expression of transgene mRNA decreased after castration of male transgenic mice. As in females, however, transgene expression could be induced after administration of testosterone. Flutamide, an androgen receptor antagonist, dose dependently blocked transgene expression in males and blunted the induction caused by testosterone in females. Neither testosterone nor estrogen altered the proximal tubule cell-specific expression of the transgene. The data suggest that the level of transgene expression in this model can be controlled temporally and in magnitude by manipulating the levels of androgen. The fortuitous androgen regulation of this transgene can be used as a molecular "on-off" switch to control transgene expression and potentially manipulate blood pressure levels in this model.
Author List
Ding Y, Sigmund CDAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AngiotensinogenAnimals
Female
Gene Expression Regulation
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Orchiectomy
Promoter Regions, Genetic
Proteins
RNA, Messenger
Sex Characteristics
Testosterone
Transcription, Genetic
