EFFECTS OF TOXIC LEVELS OF LEAD ON GENE-REGULATION IN THE MALE AXIS -INCREASE IN MESSENGER RIBONUCLEIC-ACIDS AND INTRACELLULAR STORES OF GONADOTROPHS WITHIN THE CENTRAL-NERVOUS-SYSTEM

Lead is a male reproductive toxicant. Lead exposure results in a gener al suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. To xic lead levels seem to disrupt central nervous system (CNS) control o f the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanism s accounting for the disruption of the normal function of the male axi s by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA l evels of LH and GnRH and pituitary levels of stored LH are proportiona l to blood levels of lead, we hypothesize that lead interferes with th e normal release of tropic hormones and disrupts hormonal feedback mec hanisms. The observed pleiotropic effects of lead upon the male axis a nd other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control o f specific genes.