To provide the prolactin necessary for lactation, the suckling stimulus releases pituitary lactotropes from tonic inhibition. Adaptive changes in the tuberoinfundibular dopamine (TIDA) neurons regulating prolactin appear to promote this process by producing a shift in their transmitter from dopamine (DA) to enkephalin (Enk). This """"""""phenotype"""""""" switch is accomplished by curbing synthesis of mRNA for the rate limiting enzyme of DA synthesis tyrosine hydroxylase (TH) and by inducing enkephalin (Enk) synthesis. The stimulus to suppress the TH appears to be principally neural, but the pathways that provide that suppression are not known. This proposal will determine if the pathways from the nipples to the hypothalamus initially regulate the TIDA neurons through a stimulatory relay in the peripenduncular n. that extends to the ventral arcuate before inhibiting TIDA cells. The next set of experiments will test the hypothesis that the inhibitory signal is dynorphin. Experiments will then focus on the question of what distinguishes intermittent suckling form weaning; particularly,, can the up-regulation of TH expression be interrupted if pups are returned to their damns before TH fully up-regulates, and does Enk persist after suckling cases? Lastly while hyperprolactinemia is adaptive for lactation, it can be maladaptive at other times. To understand this process, experiments will test the hypothesis that intermittent prolactin administration causes the same transmitter changes as lactation for Enk (but not TH) and that non- habituating stress induces transmitter phenotype changes in TIDA neurons that resemble those of lactation for both TH and Enk. These studies will not only provide understanding of the neural plasticity that supports lactation, but will also provides a basis for understanding neuroendocrine dysregulation of the prolactin regulating system during stress.
| Szabó, Flora Klara; Le, Wei-Wei; Snyder, Natalie S et al. (2011) Comparison of the temporal programs regulating tyrosine hydroxylase and enkephalin expressions in TIDA neurons of lactating rats following pup removal and then pup return. J Mol Neurosci 45:110-8 |
| Szabo, Flora K; Snyder, Natalie; Usdin, Ted B et al. (2010) A direct neuronal connection between the subparafascicular and ventrolateral arcuate nuclei in non-lactating female rats. Could this pathway play a role in the suckling-induced prolactin release? Endocrine 37:62-70 |
| Guidetti, Paolo; Hoffman, Gloria E; Melendez-Ferro, Miguel et al. (2007) Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia 55:78-92 |
| Koban, Michael; Le, Wei Wei; Hoffman, Gloria E (2006) Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats. Endocrinology 147:421-31 |
