PROJECT
Action of Endocrine Disrupters on Leydig Cells

Phthalates are used as plasticizers in certain infant toys and medical products and as ingredients in consumer products such as soap, shampoo, perfume, and cosmetics. As a group, phthalates act as antiandrogens, suppressing fetal testosterone biosynthesis and causing demasculinization in rodents.

A second toxicant, bisphenol A (BPA), is widely used in the manufacture of polycarbonates for food packaging and as a constituent of dental sealants. This compound is known to bind the estrogen receptor and is thus classified as a xenoestrogen. The effects of diethylhexylphthalate (DEHP) and BPA on the function of Leydig cells, the cells responsible for making testosterone, were studied to determine whether: 

1. DEHP and BPA effects are dependent on the stage of development at exposure;

2. DEHP- and BPA-related effects exerted early in development persist into adulthood; and 

3. Exposure to DEHP induces Leydig cell hyperplasia. 

Phthalates are of epidemiological significance given their ubiquitous presence in the environment. Indeed, unusually high levels of these agents were measured in the urine of young girls exhibiting premature breast development in Puerto Rico and in other human reference populations. Data indicate that DEHP effects are influenced by the stage of development at exposure, inducing changes in androgen biosynthetic enzyme activity and serum luteinizing hormone levels. Furthermore, chronic postnatal DEHP exposures: 

1. Increased gonadotropin stimulation that ultimately decreased Leydig cell steroidogenic function; and 

2. Caused aberrations in the cell division cycle that supported increased mitotic activity and Leydig cell hyperplasia (an abnormal increase in the number of cells). 

The study of BPA shows that this agent may affect reproductive activity at very low levels of exposure by suppressing pituitary and/or Leydig cell function. The affinity of BPA for the estrogen receptor may also be greater than previously thought.

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Population Council researcher
Renshan Ge

Non-Council collaborators

Gary R. Klinefelter (US Environmental Protection Agency)

Barry Zirkin (Johns Hopkins University)

Donors

US National Institutes of Health

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