Modulation of the Male Reproductive Axis by an Environmental Antiandrogen Dl (2-Ethylhexyl) Phthalate

Abstract

The endocrine disruptor hypothesis asserts that exposures to environmental agents, which have the ability to perturb the hormonal milieu, exert adverse effects on cellular differentiation and function in affected tissues. These compounds exhibit a predilection for steroid hormone receptors [androgen and estrogen receptors (AR, ER)]. Because ARs and ERs are highly expressed in reproductive tissues, it is not surprising that analysis of reproductive activity following toxicant exposures has received a great deal of attention. We have obtained data describing the effects of an antiandrogen di(2-ethlhexyl) phthalate (DEHP) on the reproductive tract of the male rat. DEHP is the most abundant phthalate in the environment, and phthalates are used to impart flexibility to infant toys, building and food-packaging products, and biomedical devices. DEHP action appears to depend on the time of exposure because prenatal exposures decreased serum luteinizing hormone (LH) and testosterone (T) levels in prepubertal rats while chronic exposures of weanling rats to DEHP caused simultaneous elevations in serum LH and T levels. The pituitary gonadotropin LH is the primary regulator of androgen biosynthesis by Leydig cells in the testis. Taken together, these observations imply that the male reproductive axis is subject to regulation by DEHP. Given the sensitivity of developing organ systems to the action of hormonally active agents, implying increased vulnerability of children to the effects of DEHP, ourfindings suggest a decrease in the levels of DEHP and other phthalates in consumer products.