Developmental Expression and Endocrine Regulation of CYP1B1 in Rat Testis

Abstract

ABSTRACT: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 17␤-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.

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…Water supplements commence on the day of surgery and should continue for 14 days. To produce animals that exhibit selective secondary hypothyroidism, hypophysectomized animals are treated with daily replacement doses of growth hormone, luteinizing hormone, follicle stimulating hormone, prolactin, testosterone propionate, 17b-estradiol benzoate, cortisone, or vehicle by subcutaneous injections (222).…”

Age-related testicular toxicity of mGluR5 negative allosteric modulators appears to be unrelated to testis drug transporter maturity

“…In developing animals, rapid growth and organ maturation, as well as differences in tissue sensitivity, metabolism, antioxidant enzyme activity, and pharmacokinetics can all contribute to the susceptibility of a tissue to chemical-induced toxicity. There is a good understanding of the maturation of antioxidant enzymes and many steroidogenic and drug metabolizing enzymes in the testis during postnatal development [36][37][38][39][40], but there is limited information regarding the maturation of drug transporters in the developing testis. This is an important area to investigate and understand given the influence of transporters on the disposition and local concentration of drugs and chemicals.…”

Morphological Examination and Transcriptomic Profiling To Identify Prednisolone Treatment in Beef Cattle

“…Testis expresses many drug-metabolizing enzymes, whose various physiological functions are not definitely known. Some isoforms are involved in xenobiotic drug metabolism, thereby probably determining testicular toxicity 38 . In cattle testis the administration of DEX alone or in combination with 17beta-oestradiol regulated the expression of some CYP isoforms (i.e.…”