Inhibition of Testosterone Production by the Environmental Estrogen Bisphenol A is Associated with Decreased Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Leydig Cells

Matthew P. Hardy, Ph.D.
Center for Biomedical Research, The Population Council
R01ES10233

Background: Synthetic estrogens have been implicated in a variety of endocrine related diseases such as hypospadias and testicular, prostate, and breast cancers. These compounds, also called xenoestrogens, are a diverse group of substances that mimic the action of the natural hormone, 17b-estradiol, in estrogen responsive tissues. Agents that cause adverse effects in target organs and tissues act by interfering with the actions of endogenous hormones and receptors. NIEHS-sponsored investigators at The Population Council have identified such effects from exposure to bisphenol A. Bisphenol A is a component of polycarbonate plastics and resins used in food packaging and dentistry.

Advance: These investigators exposed young laboratory rats to bisphenol A at low levels approximating that found in the environment. They found significant decreases in luteinizing hormone (which stimulates the production of testosterone in Leydig cells in the testis) and testosterone in serum samples. They also noted a decrease in the gene expression level of pituitary luteinizing hormone receptor and an increase in pituitary estrogen receptor gene expression. In vitro experiments with cultured Leydig cells also showed reductions in testosterone production after exposure to bisphenol A. A final set of experiments in which pregnant and nursing rats were administered bisphenol A showed a marked decrease in testosterone in testicular interstitial fluid of their male offspring.

Implication: These studies indicate that the perinatal period is a sensitive window of exposure to bisphenol A. The authors conclude that suppression of steroid hormone synthesis may be responsible for testicular abnormalities associated with bisphenol A in laboratory studies. Although there is no evidence of adverse effects in humans who consume bisphenol A orally from plastic food packaging, this exposure and the extensive use of bisphenol A in consumer products warrants more investigation of this compound at low doses for the purposes of risk assessment.

Citation: Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, and Hardy MP. Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A is Associated with Reduced Pituitary Luteinizing Hormone Secretion and Decreased Steroidogenic Enzyme Gene Expression in Rat Leydig Cells. Endocrinology 145:592-603, 2004.