Developmental expression and endocrine regulation of CYP1B1 in rat testis.
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 17beta-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.
Leung
Grace S
GS
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Kawai
Masahiko
M
Tai
Jenny K
JK
Chen
Jie
J
Bandiera
Stelvio M
SM
Chang
Thomas K H
TK
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D065633:Cytochrome P-450 CYP1B1; D017931:DNA Primers; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006728:Hormones / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000601:surgery; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000201:enzymology
D017931:DNA Primers; D006728:Hormones; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1