Disruption of Neuroendocrine Control of Luteinizing Hormone Secretion by Aroclor 1254 Involves Inhibition of Hypothalamic Tryptophan Hydroxylase Activity
Mechanisms governing the effect of polychlorinated biphenyl (PCB) toxicity on hypothalamic serotonergic function and the neuroendocrine system controlling LH secretion were investigated in Atlantic croaker ( Micropogonias unulatus ) exposed to the PCB mixture Aroclor 1254 (1 μg g body weight â1 d...
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Published in | Biology of reproduction Vol. 64; no. 3; pp. 955 - 964 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Madison, WI
Society for the Study of Reproduction
01.03.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Mechanisms governing the effect of polychlorinated biphenyl (PCB) toxicity on hypothalamic serotonergic function and the neuroendocrine
system controlling LH secretion were investigated in Atlantic croaker ( Micropogonias unulatus ) exposed to the PCB mixture Aroclor 1254 (1 μg g body weight â1 day â1 ) in the diet for 30 days. PCB treatment caused a decrease in hypothalamic 5-hydroxytryptamine (5-HT) concentrations and significant
inhibition of hypothalamic tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis, but did not alter the
activity of monoamine oxidase, the catabolic enzyme. Further, PCB treatment caused significant decreases in GnRH content in
the preoptic-anterior hypothalamic area. Significant decreases in pituitary GnRH receptor concentrations and the LH response
to the GnRH analogue (GnRHa) were also observed in PCB-exposed fish, possibly as a consequence of a decline in GnRH release.
The possible association between impaired serotonergic and neuroendocrine functions after PCB treatment was explored using
serotonergic drugs. Treatment of croaker with p -chlorophenylalanine, an irreversible TPH inhibitor, mimicked the effects of PCB on the GnRH system and the LH response to
GnRHa. Bypassing the TPH-dependent hydroxylation step with the administration of 5-hydroxytryptophan restored 5-HT to control
levels and prevented the deleterious effects of PCB on the neuroendocrine parameters. Moreover, slow-release GnRH implants
prevented the PCB-induced decline in GnRH receptors and restored the LH response to GnRHa, suggesting that GnRH therapy can
reverse PCB-induced disruption of LH secretion. These results demonstrate that TPH is one of the targets of PCB neurotoxicity
and indicate that a decrease in 5-HT availability in PCB-exposed croaker results in disruption of the stimulatory 5-HT/GnRH
pathway controlling LH secretion. |
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ISSN: | 0006-3363 1529-7268 |
DOI: | 10.1095/biolreprod64.3.955 |