Is Nitrate an Ecologically Relevant Endocrine Disruptor in Vertebrates?1

SYNOPSIS. The last three decades have brought clear recognition that many populations of animals are experiencing severe declines or local and global extinctions. Many examples have become common knowledge to the general public, such as worldwide declines in amphibian populations and extensive loss of coral reefs. The mechanisms underlying these and other changes are poorly understood. However, a growing literature indicates that a wide array of chemical contaminants have the potential to disrupt normal cell-to-cell signaling mechanisms. A global pollutant of most aquatic systems, nitrate has the potential to be an endocrine disrupting contaminant. This paper reviews studies performed on vertebrates demonstrating that nitrate and/or nitrite have the potential to alter endocrine function. Further, a retrospective study of our work on alligators from various lakes in Florida suggests that nitrate could contribute to some of the altered endocrine parameters previously reported in juvenile animals. We propose hypotheses suggesting that nitrate could alter steroidogenesis by 1) conversion to nitrite and nitric oxide in the mitochondria, the site of initial steroid synthesis, 2) altering Cl ion concentrations in the cell by substituting for Cl in the membrane transport pump or 3) binding to the heme region of various P450 enzymes associated with steroidogenesis and altering enzymatic action. Future studies are needed to examine the endocrine disruptive action of this ubiquitous pollutant. A growing literature indicates that all biologists studying natural systems, whether they choose to or not, must now consider contaminant exposure as a direct influence on their studies. That is, ubiquitous global contamination has the potential to alter the endocrine, nervous and immune systems of all organisms with resulting changes in gene expression and phenotypes.