Peroxisome Proliferator Inhibits Hormone Production in the Testis

PI: Vassilios Papadopoulos
Georgetown University

Background: Peroxisomes are small intracellular organelles that are found in high concentrations in liver cells. Their main function is detoxifying chemicals such as therapeutic drugs and chemicals such as lubricants, corrosion inhibitors, plasticizers. These compounds have become known as peroxisome proliferators because they stimulate a marked increase in the number and size of peroxisomes in liver tissue. Many of these compounds are known to cause liver cancer in laboratory animals.

In addition to their effects on the liver, peroxisome proliferators induce pathological changes in the testis. Perfluorodecanoic acid (PFDA), an industrial chemical used in some of the above processes has been reported to cause anatomical disturbances to the testis and specifically to the Leydig cells. Leydig cells in the testis produce testosterone which is necessary for normal sexual function and fertility. PFDA has also been reported to cause decreases in the circulating levels of testosterone. These researchers performed experiments to determine the mechanism by which PFDA harms the Leydig cells and inhibits testosterone production.

Advance: Working with an animal model, the researchers found that a receptor known as the peripheral-type benzodiazepine receptor (PBR) was the target of PFDA. PBR is located on the outer membrane of mitochondria where it acts as a transport mechanism for cholesterol, a precursor of testosterone.

Implication: Without properly functioning and appropriate numbers of receptors, cholesterol cannot move into the mitochondria where hormone production occurs decreasing the ability of the Leydig cells to produce normal levels of testosterone. Ultimately, these changes inhibit the production of sperm and reduce fertility. Industrial and pharmaceutical peroxisome proliferator compounds, some of which are extensively used by and for humans, may exert similar negative effects on hormone production.

Citation: Boujrad N, Vidic B, Gazouli M, Culty M, Papadopoulos V. The peroxisome proliferator perfluorodecanoic acid inhibits the peripheral-type benzodiazepine receptor (PBR) expression and hormone-stimulated mitochondrial cholesterol transport and steroid formation in Leydig cells. Endocrinology. 2000 Sep;141(9):3137-48.