Action of lead on catecholamine secretory processes of fetal hypothalamic and adrenal cells

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.