PRINCIPLES OF TOXICOLOGY - Biology East Borneo

216 REPRODUCTIVE TOXICOLOGYgonadotropin released by the pituitary gland. Gonadotropin secretion is in turn regulated by gonadotropinreleasing hormone (GnRH), secreted by the hypothalamic portion of the brain. This hierarchicalarrangement, where the hypothalamus regulates the pituitary which in turn regulates the gonads, isknown as the hypothalamic-pituitary-gonadal axis. The hypothalamic-pituitary-gonadal axis is illustratedfor both males and females in Figure 11.2. From a toxicological perspective, this arrangementcreates even more sites where toxic responses may have an impact on reproduction. With this in mind,it is not surprising that some compounds generally considered to affect the central nervous system,can impact Leydig cell function and male reproduction.The toxic effects of ethanol are wide ranging and complex. Experimental evidence for directtesticular toxicity is not clear; however, it is clear that alcoholics suffer decreased testosterone levelsand subsequently, decreased gonadal function. In alcoholics, the ability to stimulate testosteroneproduction appears to be impaired. Experimentally, it can be demonstrated that ethanol affects LHrelease. It is clear that alcohol interferes with male reproduction by affecting endocrine regulation, andultimately, in part, Leydig cell production of testosterone, but the relative contributions of directtesticular action and toxic responses elsewhere in the regulatory axis are not known.A variety of other drugs and industrial compounds also affect male reproduction through endocrinerelatedmechanisms. These include the anti-hypertensive drug propanolol, the opiates, and tetrahydrocannabinol(THC). The use of such drugs is pertinent to occupational toxicology, since their effectscan confound observations on reproductive impairment related to direct occupational exposure. Carbondisulfide, the pesticide chlordecone, and the phthalates are examples of industrial chemicals that candisrupt the endocrine axis.Besides the potential impact on spermatogenesis, there is another aspect of toxicity to thehypothalamic-pituitary-gonadal axis that affects male reproductive function. Both libido, or behavioraldrive, and physical aspects, such as penile erection and ejaculation, are controlled by the central nervoussystem. Libido is controlled primarily by androgens and any of the drugs or industrial compounds thatcan dysregulate the endocrine axis and affect androgen production can affect libido. Alcohol and THCFigure 11.2 The hypothalamic-pituitary-gonadal axis for human males and females illustrating the sequence ofcontrol from the brain to the secretion of gonadotropins by the pituitary, to the production of steroid hormones inthe gonads. The major hormonal products and their contribution to regulatory feedback loops are indicated.GnRH—Gonadotropin Releasing Hormone.