During lactation, control of the activity of the hypothalamic-pituitary-adrenal (HPA) axis is adjusted in that tonically elevated glucocorticoid secretion is observed concurrently with blunted ACTH secretion following exposure to various stressors. Although a decline in the level of CRF mRNA has been reported in neurons of the paraventricular nucleus (PVN) known to control ACTH secretion, the mechanisms underlying stress hyporesponsiveness during lactation are still largely unknown, In these studies we tested the hypothesis that pituitary responsiveness to secretagogues was altered and that central noradrenergic (NA) inputs to hypothalamic CRF neurons were modified during lactation in the rat. First, at the level of the pituitary the involvement of corticotrope sensitivity changes was examined in mid-lactating and virgin females. Results demonstrate that both virgin and lactating females show a significant ACTH response to a high stress-level dose of CRF but the magnitude of the response was greater in virgin compared to lactating females. Second, to understand the importance of brainstem NA afferents in mediating the stress response during lactation we performed 6OH-DA lesions over the PVN. In virgin females, 6OH-DA lesions caused a significant reduction in the ACTH and corticosterone (B) responses to 5 min swim stress, but lesioning did not affect stress-induced ACTH levels in lactating females. Finally, participation of central NA changes to some aspects of behavior was characterized during lactation. The acoustic startle response (ASR) was examined in groups of cycling and lactating female rats in early-, mid-, or late-lactation. / Overall results suggest that brainstem NA inputs to the PVN act to facilitate ACTH stress response in virgin, but not lactating females. The absence of this facilitation is partially due to a reduced endogenous secretion (as demonstrated under basal conditions) and to a series of modifications in alpha-adrenoreceptor number, synthesis, and function that cause a decreased responsiveness to NA in parvicellular CRF neurons. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35496 |
| Date | January 1998 |
| Creators | Bond-Toufexis, Donna. |
| Contributors | Walker, Dominique (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Neurology and Neurosurgery.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001651879, proquestno: NQ50288, Theses scanned by UMI/ProQuest. |
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