Contents | Environmental Health Perspectives 111, 3

Go to Environmental Health Perspectives homepage

Volume 111Issue 3March 2003

Research Article

Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alpha-demethylase and aromatase.

Abstract

Azole compounds play a key role as antifungals in agriculture and in human mycoses and as non-steroidal antiestrogens in the treatment of estrogen-responsive breast tumors in postmenopausal women. This broad use of azoles is based on their inhibition of certain pathways of steroidogenesis by high-affinity binding to the enzymes sterol 14-alpha-demethylase and aromatase. Sterol 14-alpha-demethylase is crucial for the production of meiosis-activating sterols, which recently were shown to modulate germ cell development in both sexes of mammals. Aromatase is responsible for the physiologic balance of androgens and estrogens. At high doses, azole fungicides and other azole compounds affect reproductive organs, fertility, and development in several species. These effects may be explained by inhibition of sterol 14-alpha-demethylase and/or aromatase. In fact, several azole compounds were shown to inhibit these enzymes in vitro, and there is also strong evidence for inhibiting activity in vivo. Furthermore, the specificity of the enzyme inhibition of several of these compounds is poor, both with respect to fungal versus nonfungal sterol 14-alpha-demethylases and versus other P450 enzymes including aromatase. To our knowledge, this is the first review on sterol 14-alpha-demethylase and aromatase as common targets of azole compounds and the consequence for steroidogenesis. We conclude that many azole compounds developed as inhibitors of fungal sterol 14-alpha-demethylase are inhibitors also of mammalian sterol 14-alpha-demethylase and mammalian aromatase with unknown potencies. For human health risk assessment, data on comparative potencies of azole fungicides to fungal and human enzymes are needed.

Table of Contents

Research Article

Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alpha-demethylase and aromatase.

Abstract

Nuclear waste transportation: case studies of identifying stakeholder risk information needs.

Abstract

Histopathologic and histochemical biomarker responses of Baltic clam, Macoma balthica, to contaminated Sydney Harbour sediment, Nova Scotia, Canada.

Abstract

Power-line frequency electromagnetic fields do not induce changes in phosphorylation, localization, or expression of the 27-kilodalton heat shock protein in human keratinocytes.

Abstract

Threshold of trichloroethylene contamination in maternal drinking waters affecting fetal heart development in the rat.

Abstract

Development and application of a robust speciation method for determination of six arsenic compounds present in human urine.

Abstract

Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities.

Abstract

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers.

Abstract

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Abstract

A geographic information system for characterizing exposure to Agent Orange and other herbicides in Vietnam.

Abstract

Estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes.

Abstract

A delta-aminolevulinic acid dehydratase (ALAD) polymorphism may modify the relationship of low-level lead exposure to uricemia and renal function: the normative aging study.

Abstract

Long-term follow-up of the residents of the Three Mile Island accident area: 1979-1998.

Abstract

Organochlorines in Swedish women: determinants of serum concentrations.

Abstract

Effects of PCB exposure on neuropsychological function in children.

Abstract

Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets.

Abstract

Association of lung function with declining ambient air pollution.

Abstract

Superfund basic research program: a model for contemporary research programs.

Letter

Importance of the Great Lakes.

Appreciation for "Remembering Alice Stewart".

Nitrate and methemoglobinemia.

Addressing global warming.

Estimating costs of environmental disease.

Research Article

PCB's legacy: fewer boys.

Article

Aluminum Floc Formation

The Beat

Low Birth Weight Linked to Asthma

Defense Cleanup

A Quick and Dirty Review

EHPnet

Acid Drainage Technology Initiative Metal Mining Sector

Research Article

From the lab to the land.

Headliners

Heme Deficiency Effects Offer Clue to Alzheimer Disease

Research Article

The earth's open wounds: abandoned and orphaned mines.

Not-so-superfund: growing needs vs. declining dollars.

Article

Organic Food for Thought

Cancer and Three Mile Island

On the Trail of Agent Orange

New Books

The Particulate Air Pollution Controversy: A Case Study and Lessons Learned

stay connected

More about ehp

SUPPORT AND RESOURCES

ABOUT EHP PUBLISHING

Request Username

Create a new account

Change Password

Your password must have 8 characters or more and contain 3 of the following:

Password Changed Successfully

Verify Phone

Congrats!