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 hypothalamic-pituitary axis. To define more precisely the toxic action of 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 secretion as reflected by an enhanced inhibition of luteinizing hormone (LH) secretion in response to the tyrosine hydroxylase inhibitor methyl-p-tyrosine (AMPT). In the control animals, the AMPT dose had no significant 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 hormone values were not statistically different between the control and lead-treated group. There were no significant differences noted in pulsatile patterns when the data were analyzed as groups. Pituitary cells harvested from lead-treated animals released significantly more LH that did the control animals. These data are consistent with the hypothesis that the signals between the hypothalamus and pituitary gland are disrupted by lead exposure in the intact animal. However, the lead-exposed castrated rat's hypothalamic-pituitary unit is able to adapt to the toxic effects of lead.
Sokol
R Z
RZ
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Berman
N
N
Okuda
H
H
Raum
W
W
D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007855:Lead Poisoning / Q000503:physiopathology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D013737:Testis / Q000502:physiology*; D019805:alpha-Methyltyrosine
D007987:Gonadotropin-Releasing Hormone; D019805:alpha-Methyltyrosine; D007986:Luteinizing Hormone