EFFECTS OF LEAD-EXPOSURE ON GNRH AND LH-SECRETION IN MALE RATS - RESPONSE TO CASTRATION AND ALPHA-METHYL-P-TYROSINE (AMPT) CHALLENGE

Animal and clinical studies suggest that lead exposure disrupts the hy pothalamic-pituitary axis. To define more precisely the toxic action o f lead on the hypothalamic-pituitary unit, a series of in vivo and in vitro experiments were performed. The first experiment was designed to determine whether lead exposure exerts an inhibitory effect on GnRH s ecretion as reflected by an enhanced inhibitiion of luteinizing hormon e (LH) secretion in response to the tyrosine hydroxylase inhibitor met hyl-p-tyrosine (AMPT). In the control animals, the AMPT dose had no si gnificant effect on LH secretion, whereas LH fell significantly in the lead-treated animals, In experiments designed to evaluate the effects of lead exposure on the pattern of pulsatile release of gonadotropins castrated control and lead-dosed animals were cannulated, and serial blood sampling was performed. Baseline LH and follicle-stimulating hor mone values were not statistically different between the control and l ead-treated group. There were no significant differences noted in puls atile patterns when the data were analyzed as groups. Pituitary cells harvested from lead-treated animals released significantly more LH tha t did the control animals. These data are consistent with the hypothes is that the signals between the hypothalamus and pituitary gland are d isrupted by lead exposure in the intact animal. However, the lead-expo sed castrated rat's hypothalamic-pituitary unit is able to adapt to th e toxic effects of lead. (C) 1998 Elsevier Science Inc.