Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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Biology of Reproduction 64, 955-964 (2001)
© 2001 Society for the Study of Reproduction, Inc.


Regular Article

Disruption of Neuroendocrine Control of Luteinizing Hormone Secretion by Aroclor 1254 Involves Inhibition of Hypothalamic Tryptophan Hydroxylase Activity1

Izhar A. Khan2,a, and Peter Thomasa

a The University of Texas at Austin, Marine Science Institute, Port Aransas, Texas 78373

ABSTRACT

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-1 day-1) 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.

FOOTNOTES

First decision: 22 September 2000.

1 This research was supported by PHS grant ESO7672. An abstract of the preliminary results was published in the Proceedings of the 4th International Symposium on Fish Endocrinology, August 2000, Seattle, WA.

2 Correspondence: Izhar A. Khan, The University of Texas at Austin, Marine Science Institute, 750 Channelview Drive, Port Aransas, TX 78373. FAX: 361 749 6777; ikhan{at}utmsi.utexas.edu







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