Dopamine (DA) is the single most potent inhibitor of luteinizing hormone (LH) release from the fish pituitary and is fundamental to the neuroendocrine control of reproduction in vertebrates. It exerts its functions through DA D1- and D2-specific postsynaptic receptors. In order for DA to be such a potent inhibitor of reproduction, I hypothesized that DA must inhibit multiple LH-stimulatory systems in the brain. I provide the first evidence that a specific DA receptor, the D2 receptor, is alternatively spliced in fish and discuss its significance in terms of the inhibitory tone of DA. A wide-scale assessment of the genes and proteins that are under the regulatory control of DAergic action is provided and begins to elucidate mechanistic pathways that DA may be modulating and showed that D1- and D2-receptor specific agonists modulate different biochemical pathways. It is then shown that DA, acting through the D1 receptor, may be modulating the effects of another neurotransmitter, glutamate, through AMPA-type receptors. Blockage of the D1 receptor resulted in a rapid and pronounced increase of activin betaa transcription and subsequent stimulation with AMPA resulted in a significant increase in isotocin and chicken-type gonadotropin-releasing hormone, concurrently with increased circulating LH levels. The hypothalamic expression of a neuronal stem cell marker, DA cell markers and developmental factors are significantly increased in the days following injection with a specific DA neurotoxin. This provides evidence for DA neuron regeneration in the adult hypothalamus, and is indicative of an intrinsic regenerative capacity of the principle hypophysiotropic LH-inhibitory system for dynamic recovery and maintenance of function after injury. Comprehensive meta-analysis of microarray data identified 268 ESTs that are very likely to be transcriptionally-regulated by DA, indicating the major influence of DA on hypothalamic function. The hypothesis that industrial pollution (pulp and paper mill effluents) inhibits reproduction in the fathead minnow was tested by determining effects on the hypothalamic gene expression. This thesis (1) characterizes the role of DA in neuroendocrine function in fish; (2) identifies a novel mechanism of LH release mediated through DA, and; (3) demonstrates an ecologically-relevant and industrial application of the findings of this thesis.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/29916 |
| Date | January 2009 |
| Creators | Popesku, Jason Theodore |
| Publisher | University of Ottawa (Canada) |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 204 p. |
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