Target organ toxicity: endocrine system. Introductory remarks: the testis.

This Target Organ Symposium is the 10th in a continuing series. Only one previous Target Organ Symposium, that on the gonads, dealt with the endocrine system. The Organizing Committee for the Endocrine Target Organ Symposium fully recognizes the diversity of scientific topics to be included into this two-day period. Nevertheless, it seemed just as defensible to include these diverse topics into one symposium as to attempt to splinter such topics in the context of toxicology. The format of the endocrine symposium is to devote separate sessions to the testes, the ovaries, the adrenal cortex, and to the thyroid gland. More specifically, each session provides an overview or state-of-the-art approach to discussing pituitary and target organ relationships. Some presentations deal with the biochemical actions of the particular target organ hormone, and finally some factors, including chemicals and environmental, that may affect these endocrine systems are discussed. This initial session focuses upon the physiology and biochemistry of the testes and those factors that affect gonadal function. To set the tone of the symposium, particularly as it relates to occupational and environmental factors and the male reproductive system, it might be of interest to recall a few recent occurrences that have received widespread attention in the popular press and newspapers. In 1977, the Metatocide, dibromo-chloropropane (DBCP), was reported to cause azoospermia or oligopsermia in men working in a California pesticide factory. The mechanism of DBCP toxicity is unknown, but it may act like an alkylating agent upon germinal epithelium. A somewhat more controversial example of chemicals contaminating the environment and adversely affecting the reproductive system is Agent Orange. Agent Orange, a herbicide, was used extensively in Vietnam to defoliate the jungle. Agent Orange is a phenoxy herbicide known as 2,4,5-T or 2,4,5-trichlorophenoxyacetic acid. There is a contaminating chemical in 2,4,5-T preparations called dioxin, also known as TCDD. TCDD is an inseparable, through unwanted contaminant of 2,4,5-T. There is some evidence, albeit not conclusive, that 2,4,5-T is a teratogen, a mutagen, and may cause impotency. Animal studies have shown that 2,4,5-T, in large doses, can adversely affect steroid metabolism (Table 1). It may be seen that varying doses of 2,4,5-T inhibit not only steroid metabolism, but also the assimilation of total tritiated testosterone by androgen-dependent organs such as the prostate. DDT is also found in the environment and can also be assimilated by male reproductive organs. Table 2 reveals the assimilation of tritiated DDT …