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    Dynamical modelling of the effect of insulin-like growth factor 1 on human cell growth : a thesis presented in fulfilment of the requirements for the degree of Master of Science in Mathematics at Massey University, Albany, New Zealand
    (Massey University, 2013) Phillips, Gemma
    Insulin-like Growth Factor-1 (IGF-1) plays a vital role in human growth and development. Interactions with IGF-1 receptors and IGF-1 binding proteins (IGFBPs) regulate IGF-1 function. Boroujerdi et al. (1997) published a mathematical model describing dynamic regulation of IGF-1. We extended the Boroujerdi et al. (1997) model to evaluate the role of cyclic Gly-Pro (CGP) in dynamic regulation of IGF-1 function. Recent research from the Liggins Institute suggests that a metabolite of IGF-1, CGP, may have a role in regulating IGF-1 homeostasis, possibly through competitive binding to IGFBPs. The goal of the research was to understand the kinetics of IGF-1, IGFBPs and CGP, along with their interactions with IGF-1 receptors. This goal and an understanding of how the kinetics mediate IGF-1 function was achieved through consideration of the nonlinear dynamics of the physiology using a modelling approach. The resulting models were directly focused on three central theories. The first is that CGP can either inhibit, stimulate or maintain IGF-1 function based on the extent of receptor binding. The other theories are that CGP regulates IGF-1 through competitive binding to IGFBPs and that CGP does not directly interact with the IGF-1 receptors. Four in vitro models were developed and fitted to experimental data. These included two implicit models which relied on two feedback terms in the equations. The second model was an alteration of the first to produce a reduction in cell number levels for high doses of CGP added to the system. The other two models were explicit models, the first of which could not express the IGF-1 dynamics well (it showed no CGP response). Although the models incorporated these theories, there are other mechanisms influencing the system which will have an effect on the data. Therefore the fourth model was introduced as a simplified version of the third. This was aimed at resembling cell culture situations more closely and was designed to have the receptor bound IGF-1 dependent on IGF-1 and CGP production rates. The models can be used to predict cellular response in an in vitro situation, or as a basis for further research in this field.
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    The role of plasma prolactin concentration in seasonal fibre growth cycles in down-producing goats and Wiltshire sheep : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University
    (Massey University, 1996) Litherland, A. J.
    This study examined the role of plasma PRL concentration in regulating seasonal fibre growth following the transition from short to long day photoperiod. In three down goat genotypes higher proportions of Angora genes extended the duration of guard hair growth, decreased biannual down growth and reduced the period of secondary follicles inactivity. The timing of follicle reactivation in spring and seasonal changes in plasma PRL concentrations were similar in all genotypes. Plasma PRL concentration increase, in spring, was associated with primary, but not secondary, follicle reactivation. Secondary follicle reactivation produced down of less than 2 mm which was associated with the shedding of winter down. Plasma PRL concentrations were suppressed, in spring and long-photoperiods (16L:8D), by injections of 1-5 mg/goat/day of bromocryptine and 2-3 weekly injections of long-acting bromocryptine (Parlodel). Injections of 1-5 mg/goat/day of domperidone elevated plasma PRL concentrations for 12 hours by and shedding was advanced. The circulating half-life of PRL, in sheep and goats, was 42±6 and 104±14 minutes following PRL injection or constant infusion respectively. In down goats, the normal spring-rise in plasma PRL concentration was suppressed using Parlodel or advanced by long day photoperiod. Increased plasma PRL concentration in spring provided anagenic signals to telogen primary and secondary follicles and catagenic signals to anagen secondary follicles. Following a reversal from short to long photoperiod anagen follicles of both goats and sheep entered telogen. Shedding occurred when the follicles subsequently reactivated. The suppression of plasma PRL concentration using Parlodel, during long photoperiod reversal, prevented the catagenic effect of long-photoperiod on anagen Wiltshire sheep follicles. In goats, however bromocryptine did not prevent follicles entering catagen but delayed follicle reactivation. The intravenous infusion of PRL had no effect on fibre growth in down goats or Wiltshire sheep. While the direct infusion of PRL to the skin caused an extreme local tissue reaction. Plasma PRL concentration has a role in regulating seasonal fibre growth cycles in down-producing goats but it is not a simple causal relationship and is dependent on follicle growth stage.