| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
, inhibits aromatase cytochrome P450 expression in the ovary of mouse
* Departments of Medical Chemistry, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
Anatomy, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
** Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan
1 To whom correspondence should be addressed. e-mail: todak{at}kochi-ms.ac.jp
Peroxisome proliferator-activated receptors (PPARs) play important roles in the metabolic regulation of lipids including steroids. In this study, we investigated whether fenofibrate, a ligand for PPAR
, could influence estrogen synthesis in vivo in the ovary of mice. As reported, chronic treatment of C57BL6/J female mice with various amounts of fenofibrate as a diet reduced the serum triglycerides level and induced hepatomegaly in a dose-dependent manner. Northern blot analyses using hepatic RNA confirmed the induction of classical PPAR-target genes including acyl-CoA oxidase and lipoprotein lipase. The analyses using ovarian RNA revealed the suppression of gene expression for enzymes involved in steroidogenesis including CYP11A, CYP19, steroidogenic acute regulatory protein, and HDL receptor, but the CYP17 expression was evidently induced. Consistent with the suppression of CYP19 mRNA expression, the aromatase activity in the ovary was dose-dependently inhibited, resulting in significant decreases in the uterine size and bone mineral density. When PPAR null mice were treated with dietary fenofibrate, neither hepatomegaly nor inhibition of ovarian aromatase activity was observed, rather the activity was enhanced.
These results demonstrate that fenofibrate inhibits ovarian estrogen synthesis by suppressing the mRNA expressions and that functional PPAR is indispensable for the inhibitory action of the agent in vivo.
Supplementary key words peroxisome proliferator-activated receptors • fenofibrate • aromatase • estrogen
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Plummer, R. M. Sharpe, N. Hallmark, I. K. Mahood, and C. Elcombe Time-Dependent and Compartment-Specific Effects of In Utero Exposure to Di(n-butyl) Phthalate on Gene/Protein Expression in the Fetal Rat Testis as Revealed by Transcription Profiling and Laser Capture Microdissection Toxicol. Sci., June 1, 2007; 97(2): 520 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yokoyama, B. Xin, T. Shigeto, M. Umemoto, A. Kasai-Sakamoto, M. Futagami, S. Tsuchida, F. Al-Mulla, and H. Mizunuma Clofibric acid, a peroxisome proliferator-activated receptor {alpha} ligand, inhibits growth of human ovarian cancer Mol. Cancer Ther., April 1, 2007; 6(4): 1379 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Corton and P. J. Lapinskas Peroxisome Proliferator-Activated Receptors: Mediators of Phthalate Ester-Induced Effects in the Male Reproductive Tract? Toxicol. Sci., January 1, 2005; 83(1): 4 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gennari, R. Nuti, and J. P. Bilezikian Aromatase Activity and Bone Homeostasis in Men J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5898 - 5907. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
