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    Modulation of Central Thyroid Hormone Regulation during Seasonal Heterothermia

    Saer, Ben

    [Thesis]. Manchester, UK: The University of Manchester; 2011.

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    Abstract

    Pronounced seasonal adaptations in physiology and behaviour are exhibited by mammals living in polar and temperate habitats. These include the development of a winter coat, altered fat reserves, reproductive quiescence and food hoarding. Maintaining constant body temperature (Tb) during winter is energetically very costly, and so many small mammals periodically abandon homeothermy in favour of heterothermy. The two principal heterothermic strategies are daily torpor and seasonal hibernation, in which bouts of profound hypothermia range from a few hours to several days (respectively). It is now clear that hypothalamic thyroid hormone (TH) regulation, and specifically the availability of the active metabolite triiodothyronine (T3), is a critical regulator of seasonal reproductive cycles in many species including birds and mammals. The impact of this signal as a switch for seasonal changes in physiology has been highlighted by the demonstration that blockade of this pathway prevents seasonal adaption in hamsters. Peripheral TH signalling is also a principle regulator of metabolic rate in mammals. Despite these findings nothing is yet known about the involvement of central (hypothalamic) and peripheral TH cycles in the expression of torpor and hibernation.Within this thesis, the role of TH dynamics both in the brain and peripheral circulation is examined within three models of heterothermia: the Siberian (Phodopus sungorus) and European (Cricetus cricetus) hamsters, which employ daily torpor and hibernation, respectively, and the laboratory mouse (Mus Musculus) which exhibits torpor in response to metabolic stress such as food restriction. To delineate TH regulation and signalling in the context of both seasonal and acute physiological responses, the expression of genes involved in thyroid hormones conversion (e.g. Deiodinase type II (Dio2) and type III (Dio3) and transport (e.g. Monocarboxylate transporter 8, Mct8) within the ependymal layer of the ventral 3rd ventricle have been detailed across seasonal (long (LD) and short day (SD) photoperiods, and during normothermic and hypothermic conditions. Furthermore, TH concentrations have been directly measured within the hypothalami of P. sungorus and C. cricetus, and TH responsive genes (e.g. Hairless (Hr) and Thyrotropin releasing hormone (TRH) to determine the potential impact of regional T3 signalling.As expected, Dio2 and Dio3 expression in P. sungorus exhibited a strong seasonal cycle indicative of elevated T3 production during SD (reduced Dio2 and elevated Dio3). Unexpectedly, total T3 measures from hypothalamic extracts revealed no significant alteration either seasonally or during torpor/hibernation in hamsters. However, Hr expression in the ependymal layer and TRH expression in the paraventricular nucleus (PVN) suggests low T3 concentrations during SD are localised to specific regions and does not encompass the whole hypothalamus per se. In addition, altered serum TH concentrations implicate seasonal and torpor associated dynamics that may play a role in seasonal adaptation and hypothermia. Finally, data from transgenic mice strongly implicate the melatonin-related receptor (GPR50) in leptin signalling and aberrant thermogenesis in mice.

    Bibliographic metadata

    Type of resource:
    Content type:
    Administered thesis
    Form of thesis:
    Traditional
    Type of submission:
    Doctoral level ETD - final
    Thesis title:
    Modulation of Central Thyroid Hormone Regulation during Seasonal Heterothermia
    Degree type:
    Doctor of Philosophy
    Degree programme:
    PhD Physiology
    Publication date:
    2011-10-25T08:30:54
    Institution:
    The University of Manchester
    Location:
    Manchester, UK
    Total pages:
    169
    Abstract:
    Pronounced seasonal adaptations in physiology and behaviour are exhibited by mammals living in polar and temperate habitats. These include the development of a winter coat, altered fat reserves, reproductive quiescence and food hoarding. Maintaining constant body temperature (Tb) during winter is energetically very costly, and so many small mammals periodically abandon homeothermy in favour of heterothermy. The two principal heterothermic strategies are daily torpor and seasonal hibernation, in which bouts of profound hypothermia range from a few hours to several days (respectively). It is now clear that hypothalamic thyroid hormone (TH) regulation, and specifically the availability of the active metabolite triiodothyronine (T3), is a critical regulator of seasonal reproductive cycles in many species including birds and mammals. The impact of this signal as a switch for seasonal changes in physiology has been highlighted by the demonstration that blockade of this pathway prevents seasonal adaption in hamsters. Peripheral TH signalling is also a principle regulator of metabolic rate in mammals. Despite these findings nothing is yet known about the involvement of central (hypothalamic) and peripheral TH cycles in the expression of torpor and hibernation.Within this thesis, the role of TH dynamics both in the brain and peripheral circulation is examined within three models of heterothermia: the Siberian (Phodopus sungorus) and European (Cricetus cricetus) hamsters, which employ daily torpor and hibernation, respectively, and the laboratory mouse (Mus Musculus) which exhibits torpor in response to metabolic stress such as food restriction. To delineate TH regulation and signalling in the context of both seasonal and acute physiological responses, the expression of genes involved in thyroid hormones conversion (e.g. Deiodinase type II (Dio2) and type III (Dio3) and transport (e.g. Monocarboxylate transporter 8, Mct8) within the ependymal layer of the ventral 3rd ventricle have been detailed across seasonal (long (LD) and short day (SD) photoperiods, and during normothermic and hypothermic conditions. Furthermore, TH concentrations have been directly measured within the hypothalami of P. sungorus and C. cricetus, and TH responsive genes (e.g. Hairless (Hr) and Thyrotropin releasing hormone (TRH) to determine the potential impact of regional T3 signalling.As expected, Dio2 and Dio3 expression in P. sungorus exhibited a strong seasonal cycle indicative of elevated T3 production during SD (reduced Dio2 and elevated Dio3). Unexpectedly, total T3 measures from hypothalamic extracts revealed no significant alteration either seasonally or during torpor/hibernation in hamsters. However, Hr expression in the ependymal layer and TRH expression in the paraventricular nucleus (PVN) suggests low T3 concentrations during SD are localised to specific regions and does not encompass the whole hypothalamus per se. In addition, altered serum TH concentrations implicate seasonal and torpor associated dynamics that may play a role in seasonal adaptation and hypothermia. Finally, data from transgenic mice strongly implicate the melatonin-related receptor (GPR50) in leptin signalling and aberrant thermogenesis in mice.
    Keyword(s):
    Thesis main supervisor(s):
    Thesis co-supervisor(s):
    Thesis advisor(s):
    Degree grantor:
    Language:
    en

    Institutional metadata

    University researcher(s):
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    Record metadata

    Manchester eScholar ID:
    uk-ac-man-scw:134262
    Created by:
    Saer, Ben
    Created:
    25th October, 2011, 07:30:55
    Last modified by:
    Saer, Ben
    Last modified:
    8th October, 2013, 19:31:11

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