Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

The Role of Estrogen Sulfotransferase in Ischemic Acute Kidney Injury

Silva Barbosa, Anne Caroline (2020) The Role of Estrogen Sulfotransferase in Ischemic Acute Kidney Injury. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Download (3MB) | Preview


Acute kidney injury (AKI) is a sudden impairment of kidney function. It has been suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase (SULT1E1/EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but the role of SULT1E1 in AKI has not been previously reported.
In this dissertation, Wild-type (WT) mice, Sult1e1 knockout (Sult1e1 KO) mice, and Sult1e1 KO mice with hepatic reconstitution of Sult1e1 were subjected to a bilateral kidney ischemia-reperfusion model of AKI, in the absence or presence of gonadectomy. Kidney injury was assessed at biochemical, histological and gene expression levels. WT mice treated with the Sult1e1 inhibitor triclosan were also used to determine the effect of pharmacological inhibition of Sult1e1 on AKI. Results showed that AKI induces the expression of Sult1e1 in a tissue- and sex-specific manner, inducing the hepatic expression of Sult1e1 in both male and female mice, but the kidney induction of Sult1e1 was only observed in male mice. A deeper investigation further demonstrated that (1) genetic knockout or pharmacological inhibition of Sult1e1 protects mice of both sexes from AKI in a sex hormone-independent manner. (2) Moreover, the effect of Sult1e1 on AKI is also tissue- and sex-specific, because transgenic reconstitution of Sult1e1 to the liver of Sult1e1 KO mice abolishes the protection in male mice, but not in female mice.
Finally, it was observed that the protective effect of Sult1e1 ablation is possibly associated with increased vitamin D receptor signaling. Overall, this dissertation elucidates a novel function
of Sult1e1 in the pathogenesis of AKI. Sult1e1 inhibitors may have their therapeutic utility in the clinical management of AKI.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Silva Barbosa, Anne Carolineacs173@pitt.eduacs1730000-0002-4933-3426
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGibbs, Robert Bgibbsr@pitt.eduGibbsr
Thesis AdvisorXie, Wenwex6@pitt.eduWex6
Committee MemberLiu, Youhualiuy@pitt.eduLIUY0000-0002-6388-9674
Committee MemberFernandez, Christianchf63@pitt.eduChf63
Committee MemberNolin, Thomas Dnolin@pitt.eduNolin
Date: 21 August 2020
Date Type: Publication
Defense Date: 17 July 2020
Approval Date: 21 August 2020
Submission Date: 4 August 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 99
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Acute kidney injury, estrogen sulfotransferase
Date Deposited: 21 Aug 2020 15:30
Last Modified: 21 Aug 2020 15:30


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item