Effect of 17-β-estradiol and testosterone on aryl hydrocarbon hydroxylase activity in mouse tissues in vivo and in cell culture

✍ Scribed by D. W. Nebert; L. L. Bausserman; R. R. Bates

• Publisher: John Wiley and Sons
• Year: 1970
• Tongue: French
• Weight: 895 KB
• Volume: 6
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910060318

✦ Synopsis

Abstract

Initiation of skin tumors by 7,12‐dimethylbenz[a]anthracene is more effective during diestrus than during estrus and thus may be inhibited by estrogens. We therefore studied the effect of sex hormones on aryl hydrocarbon hydroxylase, an enzyme system which may be a common pathway in metabolizing both polycyclic hydrocarbons and steroids.

1. The hydroxylase system is present in mouse skin and liver and is inducible by the administration of polycyclic hydrocarbons such as 3‐methylcholanthrene and 7,12‐dimethylbenz[a]anthracene. The control and inducible enzyme activities are slightly lower in castrated male mice which have received subcutaneous implants of 17‐β‐estradiol.

2. In mouse fetal cell cultures, 17‐β‐estradiol in the growth medium prevents hydroxylase induction only at concentrations 6 to 60 times greater than the level of the polycyclic hydrocarbon inducer in the medium.

3. In a cell‐free in vitro system, both 17‐β‐estradiol and testosterone competitively inhibit polycyclic hydrocarbon hydroxylation, even at levels of steroid that are lower than that of the polycyclic hydrocarbon substrate. With the hydroxylase system from mouse liver, lung, kidney, adrenal and skin in the cell‐free system, 17‐β‐estradiol is generally more inhibitory than testosterone. This difference in inhibition between an estrogen and an androgen may be related to sex differences in the metabolism of drugs and in the susceptibility to carcinogenesis by polycyclic hydrocarbons.