Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Effect of cis-platinum on heme, drug, and steroid metabolism pathways: possible involvement in nephrotoxicity and infertility.

Authors: Maines, M D

Published In Crit Rev Toxicol, (1990)

Abstract: cis-Platinum, a coordination complex of platinum, is highly effective against a number of human tumors, including steroid-dependent tumors such as testicular and prostatic cancers. It is generally assumed that DNA is the cellular target responsible for the antitumor activity of the drug. Much evidence, however, has been gathered in recent years suggesting that cis-platinum has major effects on the endocrine system, particularly the hypothalamic-pituitary-testis steroidogenesis axis, and severely disrupts the normal production of testosterone. In the axis, testis is the prime target, where the LH receptor-binding capacity of Leydig cells is decreased by nearly 80%. Within the testis, the mitochondrial cytochrome P-450scc and side-chain cleavage activity are markedly depressed and the microsomal 17 alpha-hydroxylase activity and cytochrome P-450 concentration are decreased; side-chain cleavage activity is rate-limiting in testosterone production. The effects are not limited to the testis cytochrome P-450, but extend to other organs including the liver and the kidney cytochromes. In the liver, a feminization of the cytochromes P-450 profile is produced, and hence the biotransformation of endogenous steroids as well as that of exogenous chemicals is affected. In the kidney, cis-platinum appears to be the most effective inducer of cytochrome P-450, whereby the biotransformation of the prostaglandins and fatty acids could be altered. The spectrum of the effects of cis-platinum on cytochrome P-450-dependent drug metabolism and steroid hydroxylation activity mimic those produced by hypophysectomy and are for the most part reversed by the anterior pituitary hormones. These findings suggest the possibility that general feminization of steroidogenesis caused by cis-platinum may significantly contribute to the activity of cis-platinum against hormone-dependent tumors.

PubMed ID: 2264925 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top