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dc.contributor.advisorBunn, Stephen
dc.contributor.advisorGrattan, David
dc.contributor.authorGustafson, Papillon Emelia
dc.date.available2016-11-09T02:55:23Z
dc.date.copyright2016
dc.identifier.citationGustafson, P. E. (2016). The Role of Prolactin in Suppressing the Maternal Stress Axis (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/6908en
dc.identifier.urihttp://hdl.handle.net/10523/6908
dc.description.abstractMaternal stress is associated with negative health consequences for both the mother and her offspring. To prevent these adverse outcomes, activity of the hypothalamic-pituitary-adrenal (HPA) axis is attenuated during pregnancy and lactation. While the mechanisms generating this adaptive change are not fully understood, the anterior pituitary hormone prolactin may play a significant role. Levels of prolactin (or the closely related placental lactogen) are elevated during pregnancy and lactation, and infusion of prolactin into the cerebral ventricles of rodents has anti-stress and anti-anxiety effects. The aim of this thesis was to use a mouse model to test the hypothesis that elevated prolactin signalling in the brain during pregnancy and lactation suppresses maternal HPA axis activity. Using the corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus as the marker of HPA axis activity, in situ hybridisation was used to characterise Crh mRNA expression in this nucleus in late pregnant and lactating mice, both with and without the suckling stimulus, under basal (non-stressed) conditions. Crh mRNA expression was significantly reduced in both reproductive conditions in comparison to diestrous controls. Furthermore, removal of the pups (24 h), and thus the associated suckling-induced prolactin secretion, returned Crh mRNA expression to diestrous levels. To test the role of suckling-induced prolactin secretion in suppressing Crh mRNA expression, prolactin levels were selectively manipulated in lactating mice. Maintaining elevated prolactin in the absence of suckling was sufficient to suppress Crh mRNA expression. In contrast, blocking prolactin secretion in the presence of ongoing suckling was not able to reverse the suppressive effect of lactation upon Crh mRNA expression. Thus, while prolactin was not required for the ongoing suppression of basal HPA axis activity in lactation, it remained possible that it may initiate the stress hyporesponsive state which is first apparent in pregnancy. To investigate this hypothesis, a forebrain neuron-specific prolactin receptor (PRLR) knockout mouse model was used to prevent PRLR activation during pregnancy. Despite widespread loss of PRLRs in the brain, the pregnancy-induced suppression of Crh mRNA persisted. While this indicated that prolactin may not be required for the initiation of HPA axis hyporesponsiveness, the likely incomplete knockout of PRLRs from the PVN in this model suggested that if prolactin does play a role, its target is likely located within this nucleus. As PRLR mRNA has previously been shown within the PVN, the hypothesis that prolactin acts directly upon the CRH neurons was tested using dual-label immunohistochemistry for phosphorylated signal transducer and activator of transcription 5 (pSTAT5; a marker of PRLR activation) and tdTomato (a marker of CRH neurons in a CRH-Cre reporter mouse). Despite detecting pSTAT5 in the PVN of lactating animals, no colocalisation with tdTomato was evident, indicating that the suppressive action of prolactin is not mediately directly. This thesis has confirmed the value of the mouse model in investigating the mechanisms responsible for the suppression of the maternal stress axis. These data support the hypothesis that prolactin makes a significant contribution to this adaptive response, although other factors are also likely involved.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectProlactin
dc.subjectStress
dc.subjectPregnancy
dc.subjectLactation
dc.subjectMaternal adaptation
dc.titleThe Role of Prolactin in Suppressing the Maternal Stress Axis
dc.typeThesis
dc.date.updated2016-11-09T01:55:38Z
dc.language.rfc3066en
thesis.degree.disciplineAnatomy
thesis.degree.nameDoctor of Philosophy
thesis.degree.grantorUniversity of Otago
thesis.degree.levelDoctoral
otago.interloanno
otago.openaccessAbstract Only
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