This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The non-steroidal anti-inflammatory drug, celecoxib, has been shown through in vitro studies to modulate the formation of sulfate esters of 17 -estradiol (E2) and estrone (E1) catalyzed by the sulfotransferase enzyme, SULT2A1, as well as by human liver cytosol [9] and manuscript in preparation). For both steroids, formation of the 3-sulfate metabolite was decreased in the presence of celecoxib, and for E2 the decrease in 3-sulfation was balanced by an increase in 17 -sulfation. E2-17 -sulfate is normally a very minor metabolite of E2. As yet, no studies have been conducted to determine the effect of celecoxib on estriol (E3) sulfonation, but we predict the 3-sulfation would be decreased. E1-3-sulfate and E2-3-sulfate are highly protein-bound and are transported in the blood to estrogen-sensitive tissues, including the breast, where the sulfate conjugates are hydrolyzed to the free estrogen by sulfatase. Of significance is that E2-17-sulfate is not susceptible to sulfatase. These finding have led to our hypothesis that either celecoxib itself, or a to-be-designed drug with similar effects on sulfotransferase, could be an effective adjunct treatment of estrogen-dependent breast cancer, by limiting the breast tissue exposure to estradiol. The purpose of the GCRC study is to determine if celecoxib alters the in vivo metabolism of estradiol, estrone and estriol in women, as measured by serum and urinary levels of these steroids and steroid conjugates. Demonstrating in vivo as well as in vitro effects of celecoxib on estrogen sulfation is important in substantiating our hypothesis.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Florida
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Mangal, Naveen; James, Margaret O; Stacpoole, Peter W et al. (2018) Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children. J Clin Pharmacol 58:212-220
Boissoneault, Jeff; Letzen, Janelle; Lai, Song et al. (2016) Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: an arterial spin-labeling fMRI study. Magn Reson Imaging 34:603-8
Shumyak, Stepan; Yang, Li-Jun; Han, Shuhong et al. (2016) ""Lupoid hepatitis"" in SLE patients and mice with experimental lupus. Clin Immunol 172:65-71
Hendeles, Leslie; Khan, Yasmeen R; Shuster, Jonathan J et al. (2015) Omalizumab therapy for asthma patients with poor adherence to inhaled corticosteroid therapy. Ann Allergy Asthma Immunol 114:58-62.e2
Price, Catherine C; Levy, Shellie-Anne; Tanner, Jared et al. (2015) Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson's Disease: Considerations from a Pilot Study. J Parkinsons Dis 5:893-905
Krueger, Charlene A; Cave, Emily C; Garvan, Cynthia (2015) Fetal response to live and recorded maternal speech. Biol Res Nurs 17:112-20
Jones, Jacob D; Marsiske, Michael; Okun, Michael S et al. (2015) Latent growth-curve analysis reveals that worsening Parkinson's disease quality of life is driven by depression. Neuropsychology 29:603-9
Morishita, Takashi; Foote, Kelly D; Archer, Derek B et al. (2015) Smile without euphoria induced by deep brain stimulation: a case report. Neurocase 21:674-8
Del-Aguila, J L; Cooper-DeHoff, R M; Chapman, A B et al. (2015) Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide. Pharmacogenomics J 15:153-7
Chapman, Arlene B; Cotsonis, George; Parekh, Vishal et al. (2014) Night blood pressure responses to atenolol and hydrochlorothiazide in black and white patients with essential hypertension. Am J Hypertens 27:546-54

Showing the most recent 10 out of 266 publications