DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on December 15, 2008; DOI: 10.1124/dmd.108.025635

0090-9556/09/3703-523-528$20.00
DMD 37:523-528, 2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.108.025635v1
37/3/523    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leung, G. S.
Right arrow Articles by Chang, T. K. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leung, G. S.
Right arrow Articles by Chang, T. K. H.

Developmental Expression and Endocrine Regulation of CYP1B1 in Rat Testis

Grace S. Leung, Masahiko Kawai1, Jenny K. Tai, Jie Chen, Stelvio M. Bandiera, and Thomas K. H. Chang

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada

Mammalian testis expresses xenobiotic-metabolizing enzymes, including cytochrome P450 1B1 (CYP1B1), which catalyzes the bioactivation of procarcinogens and other chemicals. The factors that control testicular expression of CYP1B1 are largely not known. In the present study, we investigated the influence of age and pituitary, gonadal, and thyroid hormones on CYP1B1 expression in rat testis. Immunoblot analysis showed that testicular CYP1B1 protein was expressed at a level of 5.9 ± 2.0 (mean ± S.E.M.) pmol/mg microsomal protein in prepubertal 22-day-old rats, whereas it was 6.6-fold greater in pubertal rats (34 days old) and 9.6-fold greater in adult rats (84–91 days old). Hypophysectomy decreased testicular CYP1B1 protein levels by 69% in adult rats when compared with intact rats of the same age. Intermittent subcutaneous administration of growth hormone to hypophysectomized adult rats further decreased it by 63%. Luteinizing hormone (LH) and follicle-stimulating hormone increased CYP1B1 expression in hypophysectomized rats, but they did not restore protein levels to those in intact adult male rats. Prolactin treatment alone had no effect; however, it potentiated the increase in CYP1B1 mRNA and protein expression by LH. 3,5,3'-Triiodothyronine, but not thyroxine, resulted in a small increase in testicular CYP1B1 protein levels. Likewise, treatment of hypophysectomized rats with testosterone propionate elicited a small increase in CYP1B1 protein expression. In contrast, treatment of intact adult male rats with 17β-estradiol benzoate decreased it by 91%. Overall, our findings indicate that rat testicular CYP1B1 protein expression is subject to developmental and endocrine control, with multiple hormones playing a role.

Address correspondence to: Thomas K. H. Chang, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada. E-mail: tchang{at}interchange.ubc.ca






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2009 by the American Society for Pharmacology and Experimental Therapeutics.