Action of Lead on Catecholamine Secretory Processes of Fetal Hypothalamic and Adrenal Cells

Abstract

The effects of lead nitrate [Pb(NO 3) 2] on tyrosine hydroxylase (TH) mass, TH mRNA, and catecholamine (CA) secretion by primary cultures of hypothalamic and adrenal cells of 18- to 22-day-old rat fetuses were investigated. Two-week-old hypothalamic and 4-week-old adrenal cell cultures were incubated for 24 h or 14 days with various concentrations (10 -10 to 10 -3 M) of Pb(NO 3) 2. In general, a 24-h exposure to low concentrations of Pb (10 -10 to 10 -7 M) suppressed the secretion of dihydroxyphenylalanine (DOPA) by hypothalamic dopaminergic cells and especially norepinephrine and epinephrine by adrenal cells; conversely, high concentrations (10 -4 and 10 -3 M) were stimulatory. This biphasic, concentration-dependent action of Pb on CA secretion occurred irrespective of the gestational age of the cell donor. Long-term (14 days) incubation of hypothalamic cells with Pb had an effect similar to that seen with a short-term incubation except that 10 -3 M Pb inhibited DOPA secretion. For adrenal cells, a long-term incubation with 10 -10 and 10 -9 M Pb inhibited CA secretion, whereas 10 -8 M was stimulatory. The TH mRNA content of the cells was not affected by Pb(NO 3) 2, regardless of its concentration. However, a 14-day incubation with low concentrations (10 -10 and 10 -9 M) of Pb resulted in an increase in TH mass in hypothalamic cells compared to controls, whereas high concentrations (10 -4 and 10 -3 M) markedly suppressed the level of TH. The effects of Pb on TH in adrenal cells were similar to those in hypothalamic cells. In conclusion, the actions of Pb(NO 3) 2 on CA secretion are biphasic: low concentrations are inhibitory, and high concentrations are stimulatory. Time of exposure does not appear to be a significant factor since a 24-h incubation with Pb was as effective as was a 14-day incubation. Thus, Pb(NO 3) 2 has a paradoxical effect on catecholaminergic cells, and in the absence of knowledge of the concentration of Pb, it is not possible to predict the toxic consequences of lead poisoning.