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PHTHALATE-INDUCED LEYDIG CELL HYPERPLASIA IS ASSOCIATED WITH MULTIPLE ENDOCRINE DISTURBANCES
Citation:
Akingbemi, B. T., R. Ge, G R. Klinefelter, B. R. Zirkin, AND M. P. Hardy. PHTHALATE-INDUCED LEYDIG CELL HYPERPLASIA IS ASSOCIATED WITH MULTIPLE ENDOCRINE DISTURBANCES. PNAS (PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES) 101(3):775-780, (2004).
Description:
The possibility that exposures to environmental agents are associated with reproductive disorders in human populations has generated much public interest recently. Phthalate esters are used most commonly as plasticizers in the food and construction industry, and DEHP is the most abundant phthalate in the environment. Daily human exposure to DEHP in the United States is estimated at 5.8 mg but occupational and clinical exposures from DEHP-plasticized medical devices such as blood bags, hemodialysis tubing and nasogastric feeding tubes may increase this level. We have investigated the effects of chronic exposures to low environmentally relevant levels of DEHP on testicular function. Our data show that prolonged exposures to this agent induced high levels of the gonadotropin LH and increased the serum concentration of sex hormones (T and E2) by more than 50%. Increased proliferative activity in Leydig cells was evidenced by increased expression of cell cycle proteins, as determined by RT-PCR. The numbers of Leydig cells in the testis of DEHP-treated rats were 40 to 60 % higher than in control rats, indicating DEHP induction of Leydig cell hyperplasia. The increasingly early onset of puberty in human populations is thought to be associated with environmental factors, and our data, showing phthalate-induced increases in serum androgen and estrogen levels provide a potential mechanism for this phenomenon. Analysis of the effects of chronic phthalate exposures on gonadotropin and steroid hormone levels should form part of overall risk assessment in human populations.